Orthopedic Ob Basic Review | Dr Hutaif Basic Science Re -...

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A Bonferroni correction is a post-hoc statistical correction made to P values when several dependent or independent statistical tests are being performed simultaneously on a single data set.
To perform a Bonferroni correction, divide the critical P value (alpha level) by the number of comparisons being made. For example, if 10 hypotheses are being tested, the new critical P value would be (alpha level)/10. The statistical power of the study is then calculated based on this modified P value.
Guyatt et al. discusses hypothesis testing and the role of alpha levels and P values. They report that the Bonferroni correction is derived from testing a dependent or independent hypotheses on a set of data and finding that the probability of a type I error is offset by testing each hypothesis at a statistical significance level divided by the number of times what it would be if only one hypothesis were tested.
Incorrect Answers:

: This describes Bayesian analysis. Answer 2: This describes Hawthorne effect. Answer 3: This describes Pearson correlation. Answer 5: This describes Study power.

**A 10-year-old child falls from a standing height and sustains the injury shown in Figure A. Her medical history includes hearing defects and the facial appearance shown in Figure B. In addition to operative fixation of her fracture she is scheduled to receive cyclical intravenous**
**pamidronate administration as a treatment after the fracture is healed. Which of the following is associated with this form of treatment?**
1) No change in bone pain

2) No change in future fracture incidence

3) An increase in osteoblast density

4) An increased risk of secondary osteosarcoma

5) An increase in bone density
**
The history and images are consistent with osteogenesis imperfecta (OI). Olecranon avulsion fractures are often seen in patients with OI and children presenting with these should be evaluated for OI. The clinical image of blue sclera can also be a characteristic finding in patients with OI. The Bisphosphonates have been shown to decrease fracture incidence and bone pain while improving bone density and overall function in OI patients.
Zeitlin et al performed a Level 5 review of OI. They state that Sillence Types I through IV are a mutation in the COL1A1 and COL1A2 genes that encode type I collagen. They report that cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and
level of ambulation.
Burnei et al also performed a Level 5 review of OI. They report that the use of bone marrow transplantation to increase osteoblast density in OI patients is currently being
researched as a potential treatment of OI.

**A 35-year-old male presents with pain and limited range of motion 3 months after arthroscopic Bankart repair of his right shoulder. His postoperative course included a continuous intra- articular infusion pump for 3 days, use of a sling for 4 weeks, and initiation of passive range of motion below the level of the shoulder. At 4 weeks postoperatively he started active range of motion exercises, and started an isotonic strengthening program at the 9 week interval. Which of the following options is the MOST appropriate step in his management?**

1) Reassurance and appropriate followup

2) Focused physical therapy on aggressive ROM exercises and modalities

3) Intra-articular injection of corticosteroids to decrease post-operative inflammation

4) Shoulder radiograph series to assess for chondrolysis

5) Arthroscopic vs open Bankart revision surgery for failed repair
**
The above patient was issued an intra-articular infusion of lidocaine for pain control after his surgery and may have developed shoulder chondrolysis. This complication after the use of intra-articular pumps has recently become more well known. The U.S. Federal drug and Administration (FDA) has issued a warning on the adminstration of continuous intra-articular infusion of local anesthestics for pain control.
The FDA has reviewed 35 cases of patients developing chondrolysis after intra- articular infusions, some being as early as 2 months after their surgery. The average time of diagnosis in these cases with chondrolysis were at an average of 8.5 months after the infusion. The majority of the reported cases occurred following shoulder surgeries. Joint pain, stiffness, and loss of motion were the most common physical complaints. As a result of their findings, the FDA issued
a warning for surgeons to be aware and monitor for signs and symptoms of chondrolysis.
Illustration A shows a radiograph consistent with chondrolysis in a patient status post arthroscopic Bankart repair. This image shows the loss of joint height in the glenohumeral joint due to chondrolysis. Also, 2 suture anchors are visible as well in the glenoid from the Bankart repair. Illustration B shows an arthroscopic image of chondrolysis and Illustrations C and D demonstrate chondrolyis viewed from an open approach.

**Regarding bone densitometry, a T-score of -3.5 is defined as which of the following?**

1) Normal bone

2) Osteopenia

3) Age appropriate bone loss

4) Osteoporosis

5) None. One cannot make this diagnosis without further information.
**
A T-score of -3.5 is defined as osteoporosis, regardless of the other clinical factors.
As described in the review by Kanis et al., the World Health Organization (WHO) has defined the following categories based on bone density in white women:
Normal bone: T-score greater than -1 Osteopenia: T-score between -1 and -2.5 Osteoporosis: T-score less than -2.5
The WHO committee did not have enough data to create definitions for men or other ethnic groups. T-score is a comparison of a patient's BMD to that of a healthy thirty-year- old of the same sex and ethnicity. Z-score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity.

**A 67-year-old female presented 2 months ago to her primary care physician with left sided thigh pain. A radiograph was taken at that time and is shown in Figure A. She was diagnosed at that time with a quadriceps strain and given a prescription for ibuprofen and physical therapy. She is now in the emergency room with severe left thigh pain and inability to bear weight on the left lower extremity after bending down to tie her shoes. She denies any constitutional symptoms. A current radiograph from the emergency room is shown in Figure B. Which of the following most likely explains this patient's fracture?**
1) Long-term corticosteroid use

2) Secondary malignancy arising from Paget disease

3) Long-term alendronate use

4) Long-term ergocalciferol use

5) Short-term teraparatide use
**
Subtrochanteric stress reaction (Figure A) and low-energy transverse fracture (Figure B) is a complication of long-term bisphosphonate use documented in the literature. Of note, a healed right sided subtrochanteric femur fracture is also visualized in Figure A.
Neviaser et al conducted a Level 4 study of 70 patients with low energy femur fractures. They found that a simple, transverse pattern and hypertrophy of the diaphyseal cortex are associated with alendronate use with 98% specificity. They report that the average alendronate usage time was 6.9 years in patients exhibiting this pattern of fracture.
Capeci et al performed a Level 4 review of alendronate therapy and its association with unilateral low-energy subtrochanteric and diaphyseal femur fractures. They recommended consideration of discontinuing alendronate with the consultation of an endocrinologist if a fracture occurs. They also recommend routine contralateral leg surveillance after to rule out contralateral stress fracture. If contralateral stress fracture is found, it it is recommended that it is treated with prophylactic intramedullary fixation.
Imaging typically shows lateral cortical thickening in the subtrochanteric femur as demonstrating on the coronal and axial CT scans shown in Illustration A and B, respectively.

**In the study by Moseley et al published in the New England Journal of Medicine, 180 patients with knee osteoarthritis were randomly assigned via sealed envelope to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Outcomes were assessed by blinded evaluators at several points over a 2 year period**
**with the use of five self-reported pain and function scores. There was a greater than 90% follow-up in the study. This study is best described as having which level of evidence?**

1) Therapeutic study, evidence level I

2) Therapeutic study, evidence level II

3) Diagnostic study, evidence level I

4) Diagnostic study, evidence level II

5) Prognostic study, evidence level I
**
Therapeutic studies investigate the results of treatment. Level 1 evidence includes randomized controlled trial with statistically significant difference or no statistically significant difference but narrow confidence interval.
A level II therapeutic study would include a lesser-quality randomized controlled trial (eg,

**A clinical trial is underway for patients with wrist extensor tendinitis. One group of 100 patients are treated with short arm casting. Another group of 100 patients are treated with physical therapy. During analysis of the results, it becomes apparent that 30 patients in the physical therapy group did not complete the full course of physical therapy. Despite not completing a full course of physical therapy, these 30 patients were included in the physical therapy group for analysis. This analysis is an example of which of the following?**

1) Per-protocol

2) Crossover analysis

3) Intent-to-treat

4) Bayesian analysis

5) Effect size
**
The following is an example of intent-to-treat analysis.
The intent-to-treat approach aims to keep similar groups similar by not
allowing for patient selection based on post-randomization outcomes (including failure to comply with the protocol). This type of analysis ensures the power of randomization so that important unknown variables that impact outcome are likely to be dispersed equally in each comparison group. Conversely, a per- protocol comparison in a clinical trial excludes patients who were not compliant with the protocol guidelines.
Berger et al., in a Level 5 review, discuss many of the principles beyond randomization that are critical for preserving the comparability of the different groups. They report that masking, allocation concealment, restrictions on the randomization, adjustment for prognostic variables, and the intent-to-treat approach to data analysis are important features of designing a good clinical trial.
Incorrect Answers:
Answer 1: Per-protocol- excludes patients who were not compliant with the protocol
guidelines
Answer 2: Crossover studies involve switching patients between different arms of the study.
Answer 4: Bayesian analysis— An analysis that starts with a particular probability of an event (the prior probability) and incorporates new information to generate a revised probability (a posterior probability).
Answer 5: Effect size— The difference in outcome between the intervention group and the control group divided by some measure of the variability, typically the standard deviation.

**A 32-year-old male is being seen in your office for evaluation of a possible rotator cuff tear. He has been seen in your office by one of**
**your partners previously after surgical treatment of a femoral shaft fracture. How much time has to pass since last evaluation or treatment in your group for this patient to revert to a new patient under CPT guidelines?**

1) 6 months

2) 1 year

3) 18 months

4) 2 years

5) 3 years
**
By CPT definition, a new patient is “one who has not received any professional services from the physician, or another physician of the same specialty who belongs to the same group practice, within the past three years.” By contrast, an established patient has received professional services from the physician or another physician in the same group and the same specialty within the prior three years.
The referenced study by Shalowitz reviewed 500 Medicare claims and found an overall coding error rate of 32.4%, with high levels of consultation coding errors. He reports that changing ambulatory consultation codes to those for new patient visits would save Medicare $534.5 million per year.
As a result of this study, as well as others, Medicare does not recognize consultation codes.

**A 55-year-old healthy female presents for a routine physical exam. When discussing bone health and osteoporosis prevention, what dose of calcium and vitamin D should be recommended for daily consumption?**

1) 1,500mg of calcium and 1,000 IUs of vitamin D

2) 2,200mg of calcium and 1,000 IUs of vitamin D

3) 750mg of calcium and 5,000 IUs of vitamin D

4) 750mg of calcium and 10,000 IUs of vitamin D

5) 2,200mg of calcium and 5,000 IUs of vitamin D
**
The National Osteoporosis Foundation recommends a daily intake of 1,200- 1500mg of calcium 800-1,000 IUs of vitamin D for adults over the age of 50.
The review article by Gehrig et al discusses the factors surrounding osteoporosis that can be modified to optimize fracture risk reduction. They report that non-prescription interventions such as calcium and vitamin D supplementation, fall prevention, hip protectors, and balance and exercise programs are treatment options.

**What is the function of the core binding factor alpha-1 (Cbfa1/Runx2)?**

1) Phosphorylation and intracellular activation of signal transducers and activators of transcription (STATs)

2) Chemotaxis of mesenchymal stem cells to sites of skeletal fractures

3) Tumor-induced osteolysis

4) Osteoclastic apoptosis

5) Osteoblastic differentiation
**
As described by Ducy et al., Cbfa1/Runx2 is a key transcription factor associated with osteoblast differentiation, skeletal morphogenesis, and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. A stop codon mutation in the Cbfa 1 gene causes cleidocranial dysplasia. Stem cell chemotaxis (moving to various sites in the body) is accomplished through a variety of cytokines, one of which is platelet derived growth factor. Tumor-induced osteolysis occurs secondary to tumor-produced cytokine activation of osteoclasts. Osteoclastic apoptosis occurs secondary to bisphosphonates.
Ballock and O'Keefe review the development, growth, and complex cytokine interaction required for normal growth plate function.

**A 20-year-old male is involved in motor vehicle collision and sustains a depressed tibial plateau fracture. When performing surgery, if calcium sulfate is used as the primary bone substitute void filler, an increase in which of the following outcomes may be expected as compared to autograft?**

1) Increased complications due to serous drainage

2) Improved clinical outcomes as shown by more rapid time to healing

3) Improved clinical outcomes as shown by SF-36 scores

4) Increased complications due to autoimmune reactions and graft rejection

5) Equivalent complication rates and clinical outcomes
**
Calcium sulfate bone graft substitute has demonstrated an increased rate of serous drainage at the surgical site. Evidence examining the use of calcium sulfate in the treatment of bone nonunions revealed a significant failure rate, suggesting that this material, used in isolation, is not optimal to promote union in that setting.
Beuerlein and Mckee reviewed the literature, showing that calcium sulfate is
an effective void filler in metaphyseal defects after impacted fracture reduction (calcaneus, tibial plateau) or simple bone cysts. However, they report that calcium sulfate is associated with serous wound drainage especially when used at subcutaneous sites and in amounts greater than 20ml.
Ziran et al present a series of 41 patients undergoing bone grafting for atrophic/avascular nonunions with adjunctive calcium sulfate-demineralized bone matrix (Allomatrix). Of the 41 patients, 13 (32%) had drainage that necessitated surgical procedures and 14 (34%) developed a deep infection.

**A 46-year-old female begins to have personality changes, cognitive decline, and chorea. Her father began having similar but less severe symptoms at age 55 before passing away 6 years later. One of her 2 older siblings has also begun to show deterioration. Which of the following describes the hereditary pattern of this disease?**

1) Autosomal dominant with variable penetrance

2) Autosomal recessive with variable penetrance

3) X-linked recessive

4) Autosomal dominant with anticipation

5) Autosomal dominant with imprinting
**
This clinical vignette describes a patient with Huntington's disease. Huntington's disease has an autosomal dominant hereditary pattern with anticipation.
Anticipation is a term used to describe trinucleotide repeat
disorders that if passed on, will present earlier and more severely in affected subjects than in their affected parent. In Huntington's disease, it is due to a "CAG" trinucleotide repeat on chromosome 4. Subjects with an affected parent have a 50% chance of inheriting the disease from them, and if present will have more severe disease.
Deighton et al provide a review on the genetics of musculoskeletal disease including the hereditary pattern of anticipation.

**All of the following are indications for locked plating technology EXCEPT:**

1) Periarticular fracture with metaphyseal comminution

2) Fracture in osteoporotic bone

3) Bridge plating for severely comminuted fractures

4) Compression plating of transverse fracture

5) Plating of fractures where anatomical constraints prevent plating on the tension side of the bone
**
Locked plates are indicated for indirect fracture reduction, diaphyseal/metaphyseal fractures in osteoporotic bone, bridging severely comminuted fractures, and the plating of fractures where anatomical constraints prevent plating on the tension side of the bone.
Locked plates and conventional plates rely on completely different mechanical principles to provide fracture fixation and in so doing they provide different biological environments for healing. Approaches to internal fixation have become more biologic. Greater emphasis is placed on vascularity and soft tissue integrity. Locked plates, analogous to rigid internal fixators, can provide relative stability favorable to secondary fracture healing. If applied appropriately, they can
avoid soft tissue compromise. The key to this new generation of plates is the locking mechanism of the screw to the plate, which provides angular stability and avoids compression of the plate to the periosteum. Favorable biomechanical and clinical results continue to expand the number of appropriate indications for use of locked plating devices, although exact indications for their use have yet to be precisely defined.
The referenced articles by Haidukewych and Egol et al are reviews of the biomechanical characteristics of locked plating technology.

**Which of the following lists these materials in order of increasing modulus of elasticity?:**

1) Cortical bone; Titanium; Cobalt-chrome; Stainless steel; Ceramic

2) Titanium; Cortical bone; Ceramic; Cobalt-chrome; Stainless steel

3) Cortical bone; Titanium; Stainless steel; Cobalt-chrome; Ceramic

4) Stainless steel; Titanium; Cortical bone; Ceramic; Cobalt Chrome

5) Cortical bone; Stainless steel; Titanium; Cobalt-chrome; Ceramic
**
Cortical bone has the lowest modulus of elasticity of the materials listed, followed by titanium, stainless steel, cobalt-chrome alloy, then ceramic.
Young's modulus of elasticity is the ratio of stress to strain, and represents the stiffness of a material and its ability to resist deformation when placed under tension. Of the materials listed, titanium has the stiffness closest to cortical bone. Ceramic has the highest modulus of elasticity, making it the most stiff of the materials listed.
Illustration A (from Miller's Review) shows the relative stiffnesses of various orthopaedically relevant materials. Young's modulus is the slope of the lines shown. Illustration B (Google images) charts their Young's Modulus.
Incorrect answers:
Answers 1, 2, 4, 5: Cortical bone is the least stiff of the materials listed. Ceramic is the stiffest. The intermediate materials listed are in the relative order listed in answer 3.

**Which of the following substances increases the chondrogenic phenotype of intervertebral disk cells and matrix synthesis?**

1) Osteoprotegrin

2) Osteonectin

3) Hyperosmotic saline

4) Corticosteroids

5) Bone morphogenic proteins

Bone morphogenic proteins have been shown to increase chondrogenic phenotype expression and increase matrix synthesis of the intervertebral disc in animal studies.
Bone morphogenetic protein-2, bone morphogenetic protein-7, and
transforming growth factor-beta are morphogens that have been shown to alter the phenotype of target cells without increasing cellular proliferation. Within the intervertebral disk, these factors have the potential to increase the chondrogenic phenotype among disk cells, and this results in the increased production of the disk matrix. Mitogenic molecules, such as insulin-like growth factor-1 and fibroblast growth factor, function to increase cellular proliferation.
Miyamoto et al. evaluated rabbits that underwent annulus fibrosus (AF) injury where they either injected a control or BMP into the nucleus pulposus. The BMP injection significantly restored disc height and improved the modulus as compared to control injections. They concluded the biochemical data suggested that the OP-1-induced restoration of the disc space was a consequence of the increased activity of anabolic pathways that resulted in biochemical changes in the IVD.
Kim et al. evaluated mRNA levels of BMP-2, BMP-7, and TGF-beta in a rabbit model of intervertebral discs. Compared to young rabbits, old rabbits generally had higher levels of mRNA expression of these three cytokines in both the annulus fibrosus and nucleus pulposus. The similar patterns of up-regulation in gene expression with age shown by these 3 anabolic cytokines suggest a common pathway in terms of regulation and transcription in the early stage of disc degeneration.
Incorrect Answers:
Answer 1: Osteoprotegrin function to limit the activity of RANKL, thus promoting net osteoblast activity and increased bone formation.
Answer 2: Osteonectin is secreted by platelets and osteoblasts and functions to regulate calcium and organizing mineral in the bone matrix.
Answer 3: Hyperosmotic saline has not demonstrated to have an effect on gene expression in intervertebral discs.
Answer 4: Corticosteroids have not been found to promote gene expression of BMP cytokines and promote matrix synthesis in intervertebral discs. Generally, corticosteroids are catabolic hormones that would likely have an inverse reaction on biochemical activities of the intervertebral disc than BMP.

**A colleague is struggling to obtain a perfect lateral radiograph for distal locking screw placement. Other than good technique, how might the surgeon best reduce the amount of radiation exposure to the patient and personnel when using fluoroscopy?**

1) The use of continuous fluoroscopy while manipulating the leg

2) Standing directly behind the cathode ray tube

3) Advising the technician to position the fluoroscopy beam on command

4) Placement of the image intensifier receptor as close to the patient as possible

5) Placement of the cathode ray tube as close to the patient as possible
**
Placing the image intensifier as close as clinically possible to the patient, scatter radiation exposure to the personnel is minimized.
Numerous steps have been described to decrease radiation in the operating room. They include:

**
The clinical presentation and images are most consistent with left hip osteonecrosis as a result of coagulation and vascular occlusion caused by sickle cell anemia.
Sickle cell disease is a genetic disorder of hemoglobin synthesis characterized by 2 abnormal hemoglobin S alleles. Under low oxygen conditions the affected blood cells become "sickle shaped" and unable to pass through vessels. This results in vascular occlusion that may have a variety of clinical consequences depending on the body part affected.
Hernigou et al. review the natural history of symptomatic osteonecrosis in adults with sickle cell disease. Once symptomatic , osteonecrosis of the hip in sickle cell disease has a high likelihood of progressing and leading to femoral head collapse. Deterioration can be rapid and in most patients operative intervention is necessary to prevent further collapse or alleviate intractable pain.
Mont et al. performed a literature review on the natural history of untreated asymptomatic osteonecrosis of the femoral head. Their findings supported that asymptomatic osteonecrosis had a high prevalence of progression to symptomatic femoral head collapse. Small, medially located lesions had a low rate of progression, while medium to large sized osteonecrotic lesions did progress in a substantial number of patients. They recommended
consideration of joint-preserving surgical treatment in asymptomatic patients with a medium-sized or large, laterally located lesion.
Figure A shows an AP pelvis with left hip osteonecrosis. Figure B shows a T2 coronal MRI with left hip osteonecrosis. Illustration A shows an example of a hemoglobin molecule which has become "sickle shaped," and as a result is unable to pass through vessels efficiently.
Incorrect Answers:

: Progressive slippage of the physis though the hypertrophic zone describes
slipped capital femoral epiphysis.
Answer 3: These radiographs are most consistent with osteonecrosis of the femoral head. There is an increased incidence of Salmonella osteomyelitis in patient with Sickle Cell disease, but Staphylococcus aureus is still the most common organism.
Answer 4: Accumulation of glycosaminoglycan breakdown products describes lysosomal disorders.
Answer 5: COL5A1 or COL5A2 mutation describes the mutation of Ehlers Danlos syndrome.

**What mechanism allows Staphylococcus epidermidis to adhere to surfaces and resist phagocytosis?**

1) Creation of active efflux pumps

2) Methylation of 23s rRNA

3) Biofilm production

4) Alteration of cell wall permeability

5) Beta-lactamase production
**
Staphylococcus epidermidis is a gram-positive bacteria that utilizes a glycocalyx/biofilm to adhere to orthopedic implants and other surfaces and resist phagocytosis.
The biofilm creates a well-protected environment where bacteria can proliferate and thrive essentially undetected by the host immune system. This leads to chronic infections of orthopedic implants that can go undetected for years.
Arciola et al note that S. epidermidis can colonize surfaces in a self-generated viscous biofilm composed of polysaccharides and that the ica genes found in
56% of S. epidermidis isolates were associated with their ability to produce biofilm.
Olson et al discuss the importance of polysaccharide intercellular adhesin (PIA), a
substance produced by 50-60% of S. epidermidis strains, in the adherence of S. epidermidis to biomaterials through biofilm creation. PIA plays a critical role in initial adherence of S. epidermidis to biomaterials, biofilm
maturation and aggregation.
Illustration A shows microscopy of Staphylococcus epidermidis, which is a gram- positive, coagulase-negative cocci. Illustration B is an overview of the different classes of organisms in microbiology.
Incorrect Answers:
Answer 1,2,4,5: Efflux pump production, hydrolysis of B-lactam drugs with beta- lactamase, alteration in cell wall permeability, and ribosomal alteration are mechanisms that Staphylococcus uses to resists antibiotics.

**Compared to cold-forged cobalt chrome, titanium alloys have which property?**

1) Increased fatigue strength

2) Increased yield strength

3) Increased endurance limit

4) Decreased ductility

5) Decreased tensile strength
**
Titanium implants have decreased tensile (ultimate) strength when compared to cobalt chrome.
Ultimate strength, or tensile strength, is the maximum stress a material can withstand before undergoing breakage or failure. The ranking of ultimate strength, from highest to lowest is: 1) cobalt chrome, 2)titanium, 3)stainless steel, and 4) cortical bone.
Young's modulus of elasticity is defined as the measure of stiffness of a material in the elastic zone. A higher Young's modulus indicates a stiffer material. While titanium is highly biocompatible with a low modulus of elasticity (Young's modulus), it has poor wear characteristics making it non- suitable for femoral heads in total hip arthroplasty.
Long et al. present a review on titanium implants with a focus on bio- mechanical properties. Their study supports previous data which showed high rates of ultra-high molecular weight polyethylene wear due to accelerated breakdown when in contact with a titanium surface.
Incorrect Answers:
Answer 1: Fatigue strength, or the maximum cyclic load (10 million cycles) that a standard sized metal can absorb before fracture, is lower in titanium compared to cobalt chrome.
Answer 2: Yield strength, or the maximal stress a material can take before permanent deformation, is decreased in titanium compared to cobalt chrome. Answer 3: Endurance limit is another way of saying fatigue strength, which is discussed in incorrect answer 1. Answer 4: Ductility, or the measure of how much strain a material can take before rupturing, is higher for titanium than cobalt chrome

**Peak bone mass attainment in both men and women is most dependent on which sex-steroid?**

1) Testosterone

2) Progesterone

3) Growth Hormone

4) Estrogen

5) Cortisol
**
Estrogen has been shown to be important for both men and women in attaining peak bone mass.
Risk factors for osteoporosis are: increasing age, female sex, early menopause, fair-skinned, family history of hip fracture, low body weight, smoking, glucocorticoid use, excessive alcohol, low protein intake, and anticonvulsant or antidepressant use.

**Which of the following contributes most to the ability of hyaline cartilage to attract water?**

1) Aggrecan

2) Biglycan

3) Decorin

4) Fibromodulin

5) Osteocalcin
**
Aggrecan molecules bind to hyaluronic acid molecules via link proteins to form a macromolecule complex, known as a proteoglycan aggregate, which attracts water.
Proteoglycans are composed of subunits known as glycosaminoglycans. Glycosaminoglycans include two subtypes: chondroitin sulfate and keratin sulfate. These glycosaminoglycans link to a protein core by sugar bonds to form an aggrecan molecule. Link proteins then stabilize many of these aggrecan molecules to hyaluronic acid to form the proteoglycan aggregate. Cartilage also contains ancillary proteoglycans that are much smaller than the aggregating proteoglycans. These small proteoglycans include decorin, biglycan, and fibromodulin. They bind to other molecules (eg, type II collagen) and assist in matrix stabilization.
Ulrich-Vinther et al. authored a Level 5 review on cartilage structure. The negative charge present within the hyaline cartilage extracellular matrix attracts cations and results in an increase in tissue osmolality. This then attracts water, which decreases the osmolality. Thus, articular cartilage has a high tissue pressure, but the presence of type II collagen matrix prevents it from swelling.
Nap et al. present a basic science review article on aggrecans. They discus that the main function of aggrecan in cartilage is to resist compressive forces.
They note that the negative charge of the aggrecan molecule disaccharides create the high osmotic swelling pressure of cartilage.
Illustration A depicts the molecular organization of an aggregated proteoglycan molecule. Incorrect Answers:
Answer 2,3,4: These are small proteoglycans that bind to other molecules (eg, type II collagen) and assist in matrix stabilization.
Answer 5: Osteocalcin is the most prevalent noncollagenous protein in bone.

**What effect do bisphosphonate medications have on spinal fusion surgery when taken in the postoperative period?**

1) Any effect can be counteracted by taking calcium supplements

2) No effect

3) Increased risk of wound infection

4) Smaller fusion mass

5) Decreased fusion rate
**
Bisphosphonates (e.g. alendronate) are used to treat osteoporosis. The mechanism of action is inhibiting the formation of the ruffled border of osteoclasts, resulting in decreasing bone turnover.
Huang et al performed a rat study comparing alendronate to placebo and found that fusion rates were lower in those treated with alendronate. However,
the fusion masses were larger in the alendronate treated rats despite lower fusion rates (why #4 is incorrect).
Lehman et al in another placebo controlled rate study found that the fusion rates for placebo (76%) were greater than the alendronate group (45%). Alendronate works on osteoclasts and does not affect calcium directly. Taking calcium should have no effect on alendronate (why #1 is incorrect). At this time there are no formal recommendations of when to stop bisphosphonate medication prior to spinal fusion surgery.

**A therapeutic study presents a systematic review of 15 high- quality randomized controlled trials with homogeneous results. What level of evidence is this considered?**

1) I

2) II

3) III

4) IV

5) V
**
A systematic review of high-quality clinical trials is considered a Level I study.
A systematic review is a powerful tool used to identify, evaluate and appraise all high- quality research related to a specific question. Systematic reviews, in contrast to most narrative review articles, adhere to strict scientific design by following eight steps; 1) defining a question and developing inclusion criteria,
2) searching for studies, 3) selecting studies and collecting data, 4) assessing risk of bias, 5) data analysis and meta-analyses, 6) addressing biases, 7) presenting results, and 8) interpreting results and drawing conclusions. When the results from the systematic review are homogeneous (less variability between studies than would be expected by chance), the data from a systematic review can be combined into a meta- analysis.
Wright et al. discuss the levels of evidence in orthopaedic journals as presented by the AAOS Evidence-Based Practice Committee. Based on levels of evidence, the AAOS provides grades of recommendation (A, B, C, I). Grade A recommendations are supported by Level 1 studies with consistent findings, whereas Grade I do not have enough evidence to support a recommendation.
Illustration A shows an "evidence pyramid." MA = meta-analysis, SR = systematic review, RCT = randomized controlled trial.
Incorrect Answers:
Answer 2: An example of a Level II study is prospective comparative study. Answer 3: An example of a Level III study is a case control trial.
Answer 4: An example of a Level IV study is a case series.
Answer 5: An example of a Level V study is one based on expert opinion.

**Progressive overloading of muscles in adults during exercise leads to which of the following?**

1) Increased muscle fiber length

2) Decreased musculotendinous junction length

3) Slowed peak contraction velocity

4) Muscle fiber hypertrophy

5) Decreased sarcomere length
**
Strength training is achieved by incremental progressive loading of muscles, in effort to increase muscle fiber contraction coordination and eventually hypertrophy of the muscle fibers themselves.
Kraemer et al. provide an American College of Sports Medicine position statement on appropriate training regimens. They recommend that loads
corresponding to 8-12 repetition maximum (RM) be used in novice training. For intermediate to advanced training, it is recommended that individuals use a wider loading range, from 1-12 RM in a periodized fashion. For local muscular endurance training, it is recommended that light to moderate loads (40-60% of 1 RM) be performed for high repetitions (> 15) using short rest periods (
**Which of the following would lead to accelerated maturation in the zone of hypertrophy at the physis?**

1) An activating mutation in TGF-ß

2) A deactivating mutation in the parathyroid hormone-related peptide (PTHrP) receptor

3) A deactivating mutation in prostaglandin E2

4) An activating mutation in the SMAD-3 protein

5) An activating mutation in the Indian Hedgehog (Ihh) protein
**
A deactivating mutation in the parathyroid hormone-related peptide (PTHrP) receptor would lead to accelerated maturation in the zone of hypertrophy.
PTHrP has been shown to play an important role in the regulation of cell proliferation at the physis. It is postulated that physeal chondrocytes regulate the local production of PTHrP by secreting a protein called Indian Hedgehog (Ihh). Ihh stimulates the chondrocytes to produce PTHrP, which slows the maturation of proliferative
chondrocytes.
Ballock et al. discuss the biology of the growth plate. With regards to cell proliferation, they describe how the proliferation of chondrocytes in the growth plate is under the control of a feedback loop involving PTHrP, Indian
Hedgehog, and TGF-ß.
Illustration A shows the Ihh/PTHrP negative-feedback loop. Incorrect Answers:
Answer 1: TGF-ß is a potent inhibitor of maturation, including cell hypertrophy, Type-X collagen expression, and alkaline phosphatase activity. An activating mutation would lead to decelerated maturation at the physis.
Answer 3: Prostaglandin E2 has not been shown to affect cell proliferation and maturation at the physis.
Answer 4: SMAD-3 increases the activity of TGF-ß. This would lead to decelerated maturation at the physis.
Answer 5: As described above, Ihh controls the release of PTHrP from chondrocytes. Activating Ihh would lead to more production of PTHrP, which would delay maturation at the physis.

**All of the following statements regarding sclerostin are true EXCEPT?**

1) It is a product of the SOST gene

2) Overexpression results in decreased bone mass

3) It is thought to be associated with sclerosteosis and Van Buchem disease

4) It activates the Wnt pathway

5) It is derived from osteocytes
**
Sclerostin inhibits the Wnt pathway, making answer choice 4 the correct answer.
Sclerostin is an osteocyte-derived negative regulator of Wnt signaling in osteoblasts. Amongst other things, the Wnt pathway and the Wnt proteins are important regulators of bone mass. They are thought to work by stimulating the production of osteoblasts. By inhibiting the Wnt pathway, sclerostin leads to decreased bone mass.
Dijke et al. discuss the role of the SOST gene in the conditions sclerosteosis and Van Buchem disease. They describe the SOST as a gene that encodes sclerostin, which is a negative regulator of Wnt signaling in osteoblasts. The
authors argue that the high bone mass seen in sclerosteosis and Van Buchem disease may be caused by increased Wnt signaling.
Day et al. review the Wnt and hedgehog signaling pathways. The Wnt and hedgehog pathways, they describe, control the differentiation of progenitor cells into osteoblasts or chondrocytes. They found that up-regulation of Wnt signaling leads to suppression of chondrocyte formation and enhanced ossification, which may be important in fracture healing.
Illustration A shows the pathway by which Wnt promotes osteoblast formation. In addition to increasing osteoblast formation, the pathway upregulates OPG, which blocks osteoclastogenesis. Illustration B shows how sclerostin inhibits
the Wnt pathway, resulting in a net decrease in bone mass. Illustration C shows an example of Van Buchem disease, an autosomal recessive disorder characterized by hyperostosis of the skull, mandible, clavicles, ribs, and diaphyseal cortices of the long bone.
Incorrect Answers:
Answers 1, 2, 3, 5: These statements are all correct regarding sclerostin.

**Which of the following is more likely to occur following a total knee arthroplasty without patellar resurfacing versus a total knee arthroplasty with patellar resurfacing in patients with rheumatoid arthritis?**

1) Patellar dislocation

2) Anterior knee pain

3) Extensor tendon rupture

4) Decreased quadriceps strength

5) Patellar clunk syndrome
**
Patients with rheumatoid arthritis who undergo a total knee arthroplasty without patellar resurfacing are more likely to have anterior knee pain when compared to the same patient population with resurfaced patellas.
Resurfacing the patella during total knee arthroplasty is a topic of controversy. Those against resurfacing note minimal issues with patellar tilt and
overstuffing the patellofemoral joint. Supporters of resurfacing state that the patellofemoral joint will eventually become arthritic if not resurfaced, and that the rate of anterior knee pain is much higher. Multiple studies, however, have shown superior results in patients with rheumatoid arthritis that have had their patella resurfaced.
Burnett et al. review the indications for patellar resurfacing during total knee arthroplasty. They consider not resurfacing the patella in patients less than 60 with non-inflammatory arthritis and a maintained patellofemoral joint space.
Holt et al. also review the role of patellar resurfacing. They mention that patellar resurfacing should be routinely done in patients with rheumatoid arthritis, preoperative patellofemoral pain, height greater than 160cm, weight greater than 60kg, or advanced patellar changes either pre- or intra- operatively.
Illustration A shows plain anteroposterior (a) and lateral (b) radiographs of the knee in a patient with rheumatoid arthritis. Degenerative changes are present in all 3 joint compartments. There is collapse of the lateral compartment with resultant valgus deformity. Erosion of the anterior aspect of the distal femoral metaphysis due to pannus is also seen.
Incorrect Answers:
Answer 1: Patellar dislocation has not been found to be higher in patellas that are not resurfaced.
Answer 3: Extensor tendon rupture is more common in patients that have had their patella resurfaced.
Answer 4: Multiple studies have not shown a difference in quadriceps strength with or without resurfacing.
Answer 5: Patellar clunk syndrome is more common in patients who have had their patella resurfaced.

**Which of the following pharmacologic treatments for osteoporosis has been associated with the potential risk for osteosarcoma development?**

1) Ergocalciferol

2) Non-nitrogen containing bisphosphonate

3) Monoclonal Ig2 against RANKL

4) Nitrogen containing bisphosphonates

5) Recombinant parathyroid hormone (1-34)
**
Recombinant parathyroid hormone (1-34) (Forteo) has been demonstrated to cause osteosarcoma in animal models but has not been to shown to cause the same effect in humans.
1-34 amino terminal residues of parathyroid hormone(1-84) administered in daily subcutaneous injections leads to bone formation. Continuous infusion leads to bone resorption.
Subbiah et al. published a case report on a patient that developed osteosarcoma following external beam radiation and recombinant teriparatide use. They discuss that though there have been nearly a 1/2 million patients treated safely with recombinant terirparatide and it is important to recognize patients that are contraindicated for treatment with recombinant teriparatide.
The FDA's Black Box warning states the following: "In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed in rats at systemic exposures to teriparatide ranging from 3 to
60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, teriparatide should be prescribed only to patients for whom the potential benefits are considered to outweigh the
potential risk. Teriparatide should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, or prior external beam or implant radiation therapy involving the skeleton)"
Incorrect Answers:
Answer 1: Ergocalciferol does not cause an increase in sarcoma
Answer 2 & 4: Bisphosphonates can cause esophagitis, dysphagia, gastric ulcers, osteonecrosis of the jaw (ONJ), and atypical subtrochanteric fractures. Answer 3: Denosumab (Prolia) can cause arthralgia, nasopharyngitis, and back pain.

**While conducting a retrospective review of patients undergoing two different techniques for open reduction and internal fixation of ankle fractures, the investigator would like to assess whether there is any significant difference between the mean patient age in the two groups. The two groups are normally distributed. Which of the following tests would be most appropriate?**

1) Student t-test

2) Analysis of Variance (ANOVA)

3) Fisher exact test

4) Kruskal-Wallis test

5) Chi-square test
**
A Student-test would be the most appropriate test for analyzing means of parametric (continuous) variables that are normally distributed between two groups.
Data can be characterized as non-parametric (categorical, ordinal) or parametric (continuous). Parametric data, such as age, are observations for which difference between the numbers have meaning on a numerical scale. Non-parametric data are observations which can be expressed as a
dichotomous (yes or no) outcome such as gender.
Kocher and Zurakowski present a Level 5 review of epidemiology and biostatistics. The authors state that univariate or bivariate analysis, such as the student t-test, is used to assess the relationship of a single independent and a single dependent variable.
Incorrect Answers:
Answer 2: Analysis of variance is used to evaluate means of parametric data between three or more groups when the data is normally distributed
Answer 3: Fisher exact test is used to compare proportions for non-parametric data when the expected frequency is small (less than five per group)
Answer 4: Kruskal-Wallis test is used to evaluate medians of three or more groups when the data are not normally distributed.
Answer 5: Chi-square test is used to compare proportions for categorical or ordinal data (non-parametric)

**Which of the following arteries provides the blood supply to the outer third of a long bone diaphysis?**

1) Nutrient artery

2) Periosteal arterioles

3) Medullary artery

4) Emissary artery

5) Perichondral artery of LaCroix
**
Periosteal arterioles (low pressure system) supply the outer third of the adult diaphyseal cortex.
Blood supply to long bone comes from three sources: 1) nutrient artery
system, 2) metaphyseal-epiphyseal system, and 3) periosteal system. Nutrient arteries (high pressure system) enter the long bone diaphyseal cortex and
then enter the medullary canal where it branches into ascending and descending arteries and supplies the inner 2/3 of the diaphysis via Haversian systems.
Bong et al. present a review article regarding intramedullary nail effects on bone healing. They report that intramedullary nails can have negative effects on endosteal and cortical blood flow but this is offset by an increase in extraosseous circulation. During early fracture healing blood flow is centripetal
(outside to inside) because high pressure nutrient artery system is often disrupted. Illustration A depicts the blood supply for the adult diaphsysis. Incorrect
Answers:
Answer 1: High pressure system that branches from major systemic arteries and supplies the inner 2/3 of mature bone.
Answer 3: The nutrient artery enters through the medullary canal and divides into ascending and descending arteries.
Answer 4: Cortical capillaries drain to the emissary venous system. There is no described emissary artery for long bones.
Answer 5: Perichondrial artery is the major source of nutrition of the growth plate

**DNA methylation, histone modification, nucleosome location, or noncoding RNA are hypothesized to contribute to the process whereby inheritable genetic alterations occur that do not involve DNA mutation. Which of the following terms best defines this process?**

1) Transgenes

2) Epigenetics

3) Gene enhancers

4) Gene promoters

5) Transformation
**
Epigenetic changes are defined as inheritable genetic alterations that do not involve DNA mutation.
The cells in a multicellular organism have almost identical DNA sequences, yet maintain different terminal phenotypes. This nongenetic cellular memory, which records developmental and environmental cues is the basis for epigenetics. DNA methylation, histone modification, nucleosome location, or noncoding RNA are hypothesized to contribute to the process.
Maher et al discuss epigenetic influences in the realm of orthopaedics. They report new data stating that increases in matrix metalloproteinase (MMP) expression in osteoarthritis is associated with altered methylation of key promoter sequences. They also report elevated levels of an enzyme involved in epigenetic gene silencing in osteoarthritis- affected chondrocytes, SIRT1, increased the expression of matrix genes and suppressed that of MMPs.
Incorrect Answers:
Answer 1: Transgenes are genes that are artificially introduced into a single- celled embryo and are present in all cells of that organism.
Answer 3: Gene enhancers are a region of a gene that positively regulates rates of transcription.
Answer 4: Gene promoters are a regulatory segment of DNA that controls start of transcription adjacent to the transcription initiation site of a gene.
Answer 5: Transformation refers to inserting a plasmid into a bacterium with added recombinant DNA.

**A 72-year-old woman presents with severe hip pain after stepping off of a curb. She denies any trauma or prior history of hip pain. Her past medical history is reviewed including a list of her current medications. Which of the following of her medications would place her at increased risk for a non-traumatic hip fracture?**

1) Phenytoin

2) Cephalexin

3) Simvastatin

4) Glipizide

5) Allopurinol
**
Phenytoin is an anticonvulsant which has been found to increase the risk of osteoporosis and, subsequently, nontraumatic fractures.
Possible mechanisms explaining the association between anticonvulsants and bone loss include hepatic induction of cytochrome P450 enzymes (increases vitamin D catabolism), direct osteoblast inhibition, impaired calcium absorption, elevated homocysteine, inhibition of response to PTH, hyperparathyroidism, reduced reproductive sex hormones, and reduced vitamin K level.
Lee et al. found that anticonvulsant use (phenobarbital, carbamazepine, phenytoin, and valproate) increases the risk of osteoporosis, and also increases the risk of fracture by 1.2 to 2.4 times.
Jette et al. found an increased fracture risk for carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin. Odds ratios ranged from 1.24 (clonazepam) to 1.91 (phenytoin).
Incorrect Answers:
Answers 2-5: These medications do not place a patient at a significant risk for non- traumatic hip fracture.

**What part of the articular cartilage has the highest concentration of proteoglycans and the lowest concentration of water?**

1) Superficial

2) Transitional

3) Deep

4) Tidemark

5) Calcified cartilage
**
This question requires that you know the 4 zones of articular cartilage: the superficial zone, the transitional zone, the deep zone (also called middle or radial zone) and the zone of calcified cartilage. The deep zone has chondrocytes with a more spheroidal shape which align themselves perpendicular to the joint surface. This zone has the largest diameter collagen fibrils, the highest concentration of proteoglycans, and the lowest
concentration of water. The collagen fibers of this zone pass into the tidemark, a thin basophilic line seen of H&E stains that corresponds to the boundary between calcified and uncalcified cartilage. Lastly the calcified cartilage zone is a thin zone of calcified cartilage that separates the radial zone (uncalcified cartilage) and the subchondral bone. The cells in this region have a smaller
volume than the cells of the radial zone, and these cells have extremely low level of metabolic activity.

**The cross-sectional area of a muscle is the factor most responsible for which of the following?**

1) Amount of maximal tension

2) Speed of contraction

3) Duration of contraction

4) Type of contraction

5) Fatigability
**
Force generation, or the amount of maximal tension that can be generated by a given skeletal muscle is most dependent on the cross-sectional area of the muscle.
The cross-sectional area is the main determining factor in force generated by the muscle and is controlled by the number of myofibrils that contract. Weight lifting can lead to muscle hypertrophy, increased cross-sectional area, and increased force (ability to lift heavier weights). Fiber types have less to do with the force of contraction and more to do with the duration and speed of contraction.
Baroni et al. investigated the chronology of neural and morphological adaptations to knee extensor eccentric training. After 12 training weeks, significant increases in strength and anatomical cross-sectional area (19%) were seen.
Illustration A shows how muscle hypertrophy from strength training increases cross- sectional area.
Incorrect Responses:
The other functional attributes of a muscle, such as speed and duration of contraction and fatigability are more predicated on muscle fiber type than on the area.

**An orthopaedic resident wants to answer a focused research question of whether mobile bearing knee arthroplasty has superior functional outcomes compared to fixed bearing knee arthroplasty. The resident mathematically combines the results from multiple retrospective cohort studies following QUORUM (Quality of Reporting of Meta-analyses) guidelines. What is the highest level of evidence that this meta-analysis can achieve?**

1) Level I

2) Level II

3) Level III

4) Level IV

5) Level V
**
The level of evidence assigned to a meta-analysis is based on the lowest level of evidence of the included studies. In this case, the studies included in the meta-analysis were retrospective cohort (Level III) studies.
A meta-analysis is a systematic review that combines the results of multiple studies to answer a focused clinical question.
Clarke discusses the QUORUM guidelines which are intended to address standards for
improving the quality of reporting of meta-analyses of clinical randomized controlled trials. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis Of Observational Studies in Epidemiology) guidelines are similar standards. A
similar set of guidelines called CONSORT (Consolidated Standards of Reporting Trials) guidelines are available for randomized trials.
Incorrect Answers:
1: Level I studies include high-quality randomized controlled trials
2: Level II studies include lower-quality RCTs and prospective cohort studies.
4: Level IV studies include case-series or poor-quality cohort and case-control studies. 5: Level V studes are expert opinion articles.

**An adolescent patient is treated with a 6mm solid intramedullary nail. Compared to a 12mm solid nail of the same material, the 6mm nail has:**

1) 1/2 the torsional rigidity

2) 1/4 the torsional rigidity

3) 1/16 the torsional rigidity

4) 1/8 the torsional rigidity

5) the same torsional rigidity
**
Nail radius affects nail bending and torsional rigidity. For a solid circular nail, the torsional rigidity is proportional to the fourth power of the radius. Thus a nail with 1/2 the diameter (6mm compared to 12mm) and therefore 1/2 the radius (3mm compared to 6mm) would have(1/2)^4 = 1/16 the torsional rigidity (answer 3). Bong et al. performed a great review of the biomechanics and biology of intramedullary nailing of the lower extremity.

**The ability of a study to detect the difference between two interventions if one in fact exists describes which of the following?**

1) Positive predictive value

2) Hawthorne effect

3) Effect size

4) Power

5) P value
**
The study power is defined as the ability of a study to detect the difference between two interventions if one in fact exists.
The power of a statistical test is correlated to the magnitude of the treatment effect, the designated type I (alpha) and type II (beta) error rates, and the sample size n. The power is equal to (1-beta) whereby beta is the false negative rate.
Kocher et al. present a Level 5 review of epidemiology and biostatistics. The review discusses study design, hypothesis testing, diagnostic performance, measures of effect, outcomes assessment, evidence-based medicine, and biostatistics. They discuss that in the orthopaedic literature power is typically set at 80%, (leaving a 20% chance that the study will display no significant association when there is an actual association.) Illustration A shows the interaction of study variables on the power of a study. Incorrect Answers:
Answer 1: Positive predictive value is the probability that a patient with a positive test actually has the disease. This value is dependent on the prevalence of disease
Answer 2: Hawthorne effect is a behavior that is changed when participants have knowledge that their behavior is being monitored.
Answer 3: Effect size is the difference in outcome between the treatment group and the control group divided by the standard deviation.
Answer 5: P value is defined as the probability, under the assumption of no difference (null hypothesis), of obtaining a result equal to or more extreme than what was actually observed if the experiment were repeated over and over

**Which of the following best describes the appearance of chondrocytes and orientation of collagen fibrils in the superficial zone of articular cartilage?**

1) Round chondrocytes oriented parallel with the tidemark and collagen fibrils oriented perpendicular to the tidemark

2) Round chondrocytes oriented parallel with the tidemark and collagen fibrils oriented parallel to the tidemark

3) Flattened chondrocytes oriented parallel with the tidemark and collagen fibrils oriented perpendicular to the tidemark

4) Flattened chondrocytes oriented perpendicular with the tidemark and collagen fibrils oriented perpendicular to the tidemark

5) Flattened chondrocytes oriented parallel with the tidemark and collagen fibrils oriented parallel to the tidemark
**
Flattened chondrocytes oriented parallel with the tidemark and collagen fibrils oriented parallel to the tidemark best describes the orientation of collagen fibrils in the superficial zone of articular cartilage.
The primary orientation of the collagen fibers in the superficial zone is parallel with the joint surface, in order to resist compressive and sheer forces. This zone is the thinnest one, and it sometimes is referred to as the gliding zone. The surface layer, known as the lamina splendens, is cell-free and composed mainly of randomly oriented, flat bundles of fine collagen fibrils. Deep to the lamina splendens are more densely packed collagen fibers interspersed with elongated, oval chondrocytes oriented parallel to the articular surface.
Sophia Fox et al. in a review article state that the superficial zone comprises 10-20% of articular cartilage and is composed of mostly type II and IX collagen.
Illustration A displays that articular cartilage has four distinct zones: (1) a superficial (tangential) zone, (2) a middle (transitional) zone, (3) a deep (radial) zone, and (4) the calcified zone. Illustration B demonstrates the collagen orientation and chondrocyte appearance in the different articular cartilage layers.
Incorrect Answers:
Answer 1-4: None of these accurately describe the appearance of
chondrocytes and orientation of collagen fibrils in the superficial zone of articular cartilage.

**A 52-year-old male underwent a right total knee arthroplasty 3 days ago and reports new onset dyspnea. His vitals signs include a temperature of 98.8, pulse of 133, blood pressure of 130/77, respiratory rate of 28, and oxygen saturation of 91% on room air. A chest radiograph shows atelectasis. Which of the following findings is most likely also present?**

1) Hyperchloremic metabolic acidosis

2) Jugular venous distention with tracheal deviation

3) EKG demonstrating S-wave in lead I Q-wave in lead III T-wave inversion in lead III

4) Pleural effusion with pleural/serum protein >0.5 and pleural/serum LDH > 0.6

5) Increased carbon monoxide diffusing capacity (DLCO)
**
The patient's clinical presentation is consistent with a pulmonary embolism and an EKG demonstrating S-wave in lead I Q-wave in lead III T-wave inversion in lead III is most likely associated with this diagnosis.
The most commonly seen signs in the EKG associated with PE are sinus tachycardia, right axis deviation and right bundle branch block. Sinus tachycardia is however only found in 8–69% of people with PE. The S1Q3T3 pattern discussed here is from acute right heart strain and is termed the "McGinn-White sign" after the initial describers but is only found in about 10-
20% of people with a PE. Patients undergoing total knee arthroplasty (TKA) without DVT prophylaxis have symptomatic PE at a rate of approximately 8%. Patients undergoing TKA have a higher risk for the presence of DVT but are at a lower risk for symptomatic PE than patients undergoing total hip arthroplasty.
Stein et al. present a study that found that dyspnea or tachypnea occurred in
92% of patients diagnosed with a pulmonary embolism. They also report that dyspnea or tachypnea was less commonly encountered in elderly patients with no previous cardiopulmonary disease.
Illustration A is a table that describes some of the characteristic findings of pulmonary embolism on a chest radiograph.
Incorrect answers:
Answer 1: Non-saddle pulmonary emboli are most often associated with respiratory alkalosis due to tachypnea.
Answer 2: Jugular venous distention with tracheal deviation is seen with tension pneumothorax.
Answer 4: Pleural effusion with pleural/serum protein >0.5 and pleural/serum LDH > 0.6 is consistent with an exudate such as pneumonia
Answer 5: Increased carbon monoxide diffusing capacity (DLCO) is not seen with pulmonary emboli.

**The estimated range of values which likely includes the unknown parameter under investigation is defined as which of the following?**

1) Standard deviation

2) Mode

3) Variance

4) Confidence interval

5) Incidence
**
When an unknown value is sought, the confidence interval gives the statistician a set of parameters within which the “true” value is located. The confidence interval is used to indicate the reliability of an estimate. The standard deviation is a quantity calculated to indicate the extent of deviation for a group as a whole. The mode is the value which
occurs most frequently in a given set of data. The variance is a quantity equal to the square of the standard deviation. The incidence is the frequency of an occurrence (or disease).

**Which of the following is true regarding the cell seen in Figure A?**
1) Originates from hematopoietic cells from a macrophage lineage

2) Derived from undifferentiated mesenchymal cells

3) They are former osteoblasts trapped in the matrix they produced

4) They become cartilage under intermediate strain and low oxygen tension

5) They form bone by producing non-mineralized matrix
**
The image shown in Figure A shows an osteoclast remodeling cortical bone through a cutting cone mechanism. Osteoclasts orginate from hematopoietic cells from a macrophage cell lineage.
Osteoclasts can be distinguished from other bone cells by their multinucleated giant cells and ruffled border on the cell periphery which increases the surface area for bone resorption. Their main function is to reabsorb bone after being stimulated by RANK-L and IL-1. A balance between osteoclast and osteoblast activity is necessary for a stable calcium level in the blood.
Caterson et al. review mesenchymal stem cells and their ability to regenerate musculoskeletal tissue. They state that potential applications include replacement of bone graft for segmental defects, nonunions, spinal fusions, and articular resurfacing.
Illustration A shows the differences between osteoblasts, osteoclasts and osteocytes. Video V describes the role and function of osteoblasts and osteocytes.
Incorrect Answers:
Answer 2: This is true of osteoblasts. Answer 3: This is true of osteocytes.
Answer 4: This is true of osteoprogenitor cells. Answer 5: This is true of osteoblasts.

**What is the equation for determining specificity of a clinical test?**

1) True negatives divided by the sum of the true negatives and false positives

2) True negatives divided by the sum of the true negatives and false negatives

3) True positives divided by the sum of the true negatives and false positives

4) True positives divided by the sum of the true positives and false negatives

5) True positives divided by the sum of the true positives and false positives
**
Specificity is the probability that a test result will be negative in patients without disease (answer 1). The sensitivity is the probability that a test result will be positive in patients with disease (answer 4). The positive predictive value is the number of patients with a positive test result who are correctly diagnosed and the negative predictive value is the opposite of this (answers 5 and 2, respectively). The referenced review article by Kocher describes many of the statistical tools useful for practicing orthopaedic surgeons.

**Which of the following graft materials has the least potential to elicit an immune response?**

1) Fresh irradiated corticocancellous bulk allograft

2) Fresh frozen fibular strut allograft

3) Fresh frozen Achilles tendon allograft

4) Fresh Achilles tendon allograft

5) Freeze dried cancellous bone chips

Of the options listed, freeze dried cancellous allograft has the least potential to elicit an immune response. Remember, all allograft tissue has more of an immune response generating capability than autograft tissue, which has the least of any of these materials.
All allograft materials carry immunogenic properties, which decrease as the material is processed via the various sterilizing, freezing, or drying process(es). As the processing increases, the mechanical characteristics of the graft tends to decrease.
Ahlmann et al. compared the complications associated with harvesting iliac crest bone graft from the anterior crest and posterior crest. They found the rates of both minor complications (p = 0.006) and all complications (p =
0.004) were significantly higher after the anterior harvest procedures than they were after the posterior procedures. They recommend that iliac crest bone graft be harvested posteriorly whenever possible.
Incorrect Answers:
Answer 1: Most bone and soft tissue allografts undergo irradiation to remove bacteria or other infectious agents, but this does not prevent an immune
response in itself.
Answer 2: Fresh frozen allografts have more immunogenic potential than freeze dried, but less than fresh materials. Fresh allograft is not typically utilized, as the processing of allograft (bone or soft tissue) provides the safety of minimizing infectious disease transmission.
Answer 3: Fresh frozen allografts have more immunogenic potential than freeze dried, but
less than fresh materials. Thus fresh Achilles tendon allograft has the highest immunogenicity.
Answer 4: Fresh Achilles tendon allograft will elicit the greatest immunogenic response.

**Which of the following statements is correct regarding Vitamin D?**

1) 1,25-dihydrocholecalciferol is the best laboratory study to determine a Vitamin D deficiency

2) 25-hydroxycholecalciferol is the active form of Vitamin D

3) 24,25-dihydroxycholecalciferol is an inactive form of Vitamin D

4) 1,25-dihydrocholecalciferol is converted to 25-hydroxycholecalciferol in the kidney

5) The half-life of 1,25-dihydrocholecalciferol is longer than 25- hydroxycholecalciferol
**
24,25-dihydroxycholecalciferol in an inactive form of Vitamin D. High levels of
1,25-dihydroxyvitamin D stimulate the enzymatic production of 24,25- dihydroxyvitamin D, the inactive form of vitamin D, thereby self-regulating the action of 1,25-dihydroxyvitamin D.
Vitamin D is paramount to proper calcium homeostasis and has important clinical implications in the orthopaedic patient. Vitamin D3 is synthesized in the skin and is converted to 25-hydroxycholecalciferol in the liver. 25- hydroxycholecalciferol is then converted in the kidney into 1,25- dihydroxycholecalciferol, the active form of vitamin D. The best test to determine Vitamin D deficiency is the measurement of 25- hydroxycholecalciferol, as it has a longer half-life and circulating levels are
1,000x more than 1,25-dihydrocholecalciferol.
Patton et al. review the importance of Vitamin D in the orthopaedic patient. They discuss the implications of Vitamin D deficiency, and urge orthopaedic surgeons to be proficient in both the diagnosis and treatment of the condition.
Bogunovic et al. measured the levels of 25-hydroxycholecalciferol in 723 patients who were to undergo orthopaedic surgery. 40% of these patients were noted to be deficient in Vitamin D, with the highest rates in patients scheduled to undergo trauma and sports surgery.
Illustration A reviews Vitamin D metabolism. 24,25-dihydroxycholecalciferol is referred to as pre-Vitamin D.
Incorrect Answers:
Answer 1: 25-hydroxycholecalciferol is the best laboratory study to determine
Vitamin D deficiency due to its long half-life and high circulating levels. Answer 2: 1,25- dihydroxycholecalciferol is the active form of Vitamin D. Answer 4: 25- hydroxycholecalciferol is then converted in the kidney into 1,25- dihydroxycholecalciferol. Answer 5: The half-life of 25-hydroxycholecalciferol is 2-3 weeks, while the
half-life of 1,25-dihydrocholecalciferol is only 4-6 hours.

**You are the team physician for a collegiate football team and receive weekly injury reports from the athletic trainer. All players with sickle-cell trait are listed at the bottom to remind all on-field**
**personnel that they may need which of the following?**

1) Oxygen supplementation and oral or IV hydration

2) Additonal layers of warm clothes

3) Increased pain medication

4) Avoidance of non-steroidal anti-inflammatory medicines

5) Days of rest due to increased joint pain
**
Players with a blood test indicating the presence of sickle-cell trait (SCT) are at risk for exertional sickling collapse which responds initially to rest, hydration and oxygen.
SCT is not a disease but a condition, resulting from inheritance of one gene for sickle hemoglobin (S) and one gene for normal hemoglobin (A).
The vital concern is exertional sickling collapse, which can be fatal, occurs in a variety of sports, and is a leading cause of death in college football.
According to the review by Eichner, sickling collapse is an “intensity”- associated syndrome that differs from the other common causes of collapse. The best approach in college football may be tailored precautions to prevent sickling collapse and enable athletes with SCT to thrive. Other clinical concerns in SCT are compartment syndromes and lumbar myonecrosis, splenic infarction, gross hematuria, hyposthenuria, and venous thromboembolism.
Kark et al. reviewed all cases of sudden death occurring among 2 million enlisted recruits during basic training in the U.S. Armed Forces from 1977 to
1981/. They concluded that "recruits in basic training with the sickle-cell trait have a substantially increased, age-dependent risk of exercise-related sudden death unexplained by any known preexisting cause".
Incorrect Responses:
2/. no research to support need for warmer clothes and cases occur year round. 3&5/. these are typical of sickle cell disease, not SCT.
4/. important in patients with renal impairment, which is not typically seen in SCT.

**A physician is interested in using platelet-rich plasma (PRP) for treatment of osteochondral lesions of the talus. He is reviewing a prospective cohort study that compares 40 patients treated with PRP and cast immobilization for 6 weeks vs. 36 patients treated conservatively with cast immobilization for 6 weeks. All patients were treated at the same time and institution. The study was not randomized although treatment and control groups were matched**
**appropriately to reduce selection bias. Follow-up in each group was**
**> 80% over 1 year. The paper reported significant improvement with use of PRP based on three standard foot and ankle outcome scores (AOFAS, SF-36, FOAS). What is the level of evidence for this study?**

1) Level I

2) Level II

3) Level III

4) Level IV

5) Level V
**
This is prospective cohort study with Level-II evidence.
Level of evidence provides guidance to the study quality. It is used to assess therapeutic studies (as with this question), prognostic studies, diagnostic studies and economic or decision models. When determining the level of evidence, readers must critically appraise the study question, treatment, intervention and outcomes of the study design. Level-II therapeutic studies consist of well-designed prospective cohort studies, poor-quality randomized controlled trials (follow-up less than 80%) and systematic review of Level-II studies or non-homogenous Level-I studies.
Wright et al. provided an excellent summary of clinical research study level of evidence. This has been provided as Illustration A.
Illustration A shows a chart of level of evidence. There is a column for each type of study which corresponds to a row that outlines the level of evidence based on study
design.
Incorrect Answers:
Answer 1: Level-I evidence include randomized controlled studies with follow- up>80% and systematic review of Level-I RTC studies (homogenous studies) Answer 3: Level-III evidence include case control studies, retrospective cohort studies and systematic review of Level-III studies
Answer 4: Level-IV evidence include case series with no control group (or compare to a historical control group)
Answer 5: Level V evidence include expert opinion

**Low serum phosphate and normal calcium levels are found in what common etiology of hereditary rickets?**

1) X-linked hypophosphatemic

2) Vitamin D-dependent, type I

3) Vitamin D-dependent, type II

4) Autosomal dominant hypophosphatemic

5) Jansen's metaphyseal chondrodysplasia
**
Low serum phosphate and normal calcium levels are found in X-linked hypophosphatemic rickets.
X-linked hypophosphatemic rickets is the most common form of hereditary rickets. It is an X-linked dominant disorder which has been linked to the PHEX gene. Laboratory findings
of this disorder include low serum phosphate, normal serum calcium and 25 hydroxycholecalciferol levels, and inappropriately low 1,25-dihydroxyvitamin D3.
Carpenter et al. showed hypophosphatemic rickets was initially referred to as “vitamin D resistant rickets” due to its lack of response to therapeutic vitamin D. Current treatment with activated vitamin D metabolites (calcitriol or
alfacalcidol) and phosphate salts have been shown to help with this condition.
Illustration A shows an insufficiency fracture of the proximal tibia in an adult patient with X-linked hypophosphatemic rickets. A stress fracture on the medial tibia may be a presenting feature of untreated disease.
Incorrect Answers:
Answer 2: Vitamin D-dependent rickets, type I, is a rare autosomal recessive disorder. Answer 3: Vitamin D-dependent rickets, type II, is a rare autosomal recessive disorder, most often caused by mutations in the vitamin D receptor gene. Answer 4: Autosomal dominant hypophosphatemic results from a rare mutation in the fibroblast growth factor 23 (FGF23) gene.
Answer 5: Jansen's metaphyseal chondrodysplasia is a skeletal dysplasia that results from ligand-independent activation of the type 1 parathyroid hormone
receptor (PTHR1).

**A healthy patient undergoes routine pre-operative laboratory testing and is found to have a leukocyte count of 1.5 × 10(9) cells/L. When the historical records are examined, this is found to be the patients base-line level over a period of years. Which of the following statements is most likely to be true:**

1) The patient is at a significantly higher risk of surgical infection

2) The patient is more likely to be of African than of European descent

3) The patient is more likely to be of European than of Middle Eastern descent

4) The patient is more likely to be a non-athlete than an athlete

5) The patient is more likely to be female than male
**
The clinical presentation is consistent with Benign Ethnic Neutropenia, a condition in which a patient has chronic, benign, inborn and lifelong absolute neutrophl count below population mean. This condition is found in the U.S. to be most common in African- Americans, some groups of Middle Eastern patients, males, children under 5 years old, and athletes compared to non- athletes.
A standardized level at present for abnormally low absolute neutrophil count (ANC) is below 1.5 x 10(9) cells/L, however this may not have clinical or scientific relevance as a cutoff point, particularly in the affected Ethnic groups. Fewer than 1% of all populations have absolute neutrophil count
**A 14-year-old patient has sustained a complete ACL tear of his right knee. Which of the following options has shown to be the most limiting factor for access to pediatric orthopaedic management in the United States?**

1) Sex of the patient

2) Type of health insurance

3) Child greater than 10 years of age

4) Acute knee injuries requiring operative treatment

5) Timing of the referral
**
The type of health insurance in the pediatric population has shown to be a significant factor for access to specialized healthcare in the United States.
Access to pediatric orthopaedic management has been well investigated. Numerous Level 4 studies have shown that orthopaedic offices in urban and rural areas prefer treating patients with private insurance over patients with Medicaid.
Iobst et al. telephoned 100 urban and rural orthopaedic outpatient offices to schedule an appointment for a 10-year-old patient with a forearm fracture. They showed that 8/100 offices would schedule an appointment within 1 week to the child with Medicaid insurance, as compared to 36/100 that gave an appointment to a child with private insurance.
Pierce et al. contacted 42 orthopaedic practices to schedule an appointment for a 14- year-old patient with an ACL injury. They showed that 38/42 offices scheduled an appointment for the child within 2 weeks with private insurance. This compared to 6/42 that scheduled an appointment for a similar child with Medicaid.
Incorrect Answers:
Answers 1,3,4,5: The limiting determinant to healthcare in the pediatric population has shown to be the type of health insurance. Sex, age of child, operative vs nonoperative injuries and timing of referral have not been shown to affect access to healthcare.

**The perioperative use of which medication has been shown to increase the risk of post-operative infection following orthopaedic procedures in patients with rheumatoid arthritis (RA)?**

1) Naproxen

2) Leflunomide

3) Sulfasalazine

4) Etanercept

5) Aspirin
**
Of the medications listed, only etanercept has been shown to increase the risk of post- operative infection following orthopaedic procedures in patients with RA.
Etanercept is a TNF-alpha antagonist with a short half-life that is administered once or twice weekly in patients with RA. Since TNF-alpha plays a central role in the pathogenesis of RA and is instrumental in causing joint destruction, the inhibition of this molecule has shown excellent results in controlling disease. The most powered study on TNF-alpha inhibitor use in the perioperative period following an orthopaedic procedures demonstrated a significant increase in
post-operative infection.
Howe et al. review the medical management of patients with RA who underwent orthopaedic procedures. They state that while there is conflicting information regarding TNF-alpha antagonists, they recommend holding them prior to major orthopaedic interventions.
Giles et al. review 91 patients with rheumatoid arthritis who underwent an orthopaedic procedure. They found TNF-alpha inhibitor therapy to be significantly associated with the development of a serious postoperative infection (p=.041)
Perhala et al. review 61 patients with RA who were treated with methotrexate during the perioperative period surrounding a total joint arthroplasty. They
failed to find a significant increase in complications in this patient group, stating the perioperative use of methotrexate does not affect wound healing or increase the likelihood of periprosthetic infection.
Illustration A shows the site of action of TNA-alpha inhibitors in the RA pathway.
Incorrect Answers:
Answer 1: Naproxen should be discontinued 3 days prior to surgery because of its ability to increase bleeding time and the subsequent potential for increased blood loss.
Answer 2: Leflunomide is an inhibitor of pyrimidine synthesis. It has not been shown to increase the risk of post-operative infection.
Answer 3: Sulfasalazine's mechanism of action is largely unknown, but it has not been shown to increase the risk of post-operative infection.
Answer 5: Aspirin has not been shown to increase infection if continued in the perioperative period.

**Communication breakdown is the leading cause of which of the following?**

1) Delayed diagnoses

2) Medication errors

3) Surgical site infections

4) 1 and 2

5) All of the above
**
Communication failures are the leading cause of wrong side surgeries, medication errors and diagnostic delays.
Poor communication sets up environments in which medical errors can take place. Per the Joint Commission, medical errors may be the among the top 10 causes of death in the United States. Establishing open lines of communication is critical to reduce the risk of error and enhance patient safety.
Gandhi et al. designed a framework to study missed or delayed diagnoses and their causes. The most significant factors contributing to errors were poor handoffs, failures in judgment, failures in memory and failures in knowledge.
O’Daniel et al. review the importance of professional communication and collaborative team efforts. They note that patient safety is at risk when poor communication is in place. The leading cause for medication errors, treatment delays and wrong-site surgeries is communication failure.
Illustration A shows the leading causes of death in the United States. This includes “preventable errors” as a cause.
Incorrect Answers:
Answers 1, 2: Communication failures can lead to delays in diagnosis and
treatment, medication errors and wrong side surgery
Answers 3, 5: Communication failure is not a direct contributor to surgical site infection

**Which of the following is true regarding osteoprotegerin (OPG)?**

1) It is secreted by osteoclasts

2) It increases bone resorption

3) Binds to prostoglandin E2 before stimulating osteoclasts

4) Osteoprotegerin knock-out mice develop osteopetrosis

5) Binds to and sequesters RANKL
**
Osteoprotegerin is a decoy receptor for RANKL. Binding to RANKL causes decreased production of osteoclasts by inhibiting the differentiation of osteoclast precursors.
Bone resporption/remodeling is a complex process regulated by a large variety of molecules. Molecules that have shown to inhibit osteoclasts include OPG, calcitonin, estrogen, TGF-B, and IL-10. Corticosteroids have been shown to decrease production of OPG, thereby enhancing osteoclast formation and longevity. Prolia, or denosumab, is a newly approved drug used to treat osteoporosis and has a mechanism of action similar to osteoprotegerin
(inhibits binding of RANKL to RANK).
Boyle et al. review osteoclast differentiation and activation. The authors state that targeted disruption of OPG causes increased osteoclastogenesis and/or activation resulting in osteopenia.
Illustration A shows how OPG binds to RANKL inhibiting the stimulation of osteoclasts.
Incorrect Answers:
Answer 1: OPG is secreted by osteoblasts.
Answer 2: OPG decreases bone resorption by inactivating RANKL. Answer 3: OPG does not bind to prostoglandin E2, nor does it stimulate osteoclasts.
Answer 4: RANKL knock-out mice creates an osteopetrosis-like condition.

**A 55-year-old woman has T-score -2.0 at the femoral neck. According to the World Health Organization Fracture Risk Assessment Tool (FRAX), she has a ten- year probability of sustaining a hip fracture of 1.5% and a ten-year probability of sustaining a major osteoporotic fracture of 8.9%. Which of the following statements is true regarding her antiresorptive therapy management?**

1) Antiresorptive therapy should be started based on her T-score

2) Antiresorptive therapy should be started based on her risk of hip fracture alone

3) Antiresorptive therapy should be started based on her risk of major osteoporotic fracture alone

4) Antiresorptive therapy should not be started

5) Antiresorptive therapy should be started based on her risks of both hip fracture and major osteoporotic fracture
**
This patient has osteopenia. Assessment by FRAX shows that ten-year risk of hip fracture is less than 3% and her ten-year risk of major osteoporosis- related fracture is less than 20%. Therefore, antiresorptive therapy is not indicated at this time.
According to the 2008 National Osteoporosis Foundation guidelines, pharmacologic treatment for osteoporosis should be considered if patients are
postmenopausal women or men greater than 50 years old AND meet one of the following criteria: (1) they have a prior hip or vertebral fracture, (2) they have a T score -2.5 or less at the femoral neck or spine, (3) they have a T score between -1.0 and -2.5 at the femoral neck or spine AND a 10-year risk of hip fracture greater than 3% or 10-year risk of major osteoporosis-related fracture greater than 20%.
FRAX (World Health Organization Fracture Risk Assessment Tool) calculates
10-year risk of fracture based on the following variables: age, sex, race, height, weight, BMI, history of fragility fracture, parental history of hip fracture, use of oral glucocorticoids, secondary osteoporosis and alcohol use to calculate 10-year risk of fracture.
Unnanuntana et al. reviewed the assessment of fracture risk. Besides FRAX score and T-score, they discussed biochemical markers of bone formation and resorption, which are useful for monitoring the efficacy of antiresorptive / anabolic therapy, and may help identify patients at high risk for fracture.
Ekman et al. reviewed the role of the orthopaedic surgeon in minimizing mortality and morbidity associated with fragility fractures. The surgeon should consider prescribing appropriate medications, physical therapy, assessing fall risk and preventing falls and changing lifestyle factors (exercise, smoking and alcohol).
Illustration A shows the FRAX online tool ([_http://www.shef.ac.uk/FRAX/tool.aspx?country_ _=__=9)._ Illustration B shows the](http://www.shef.ac.uk/FRAX/tool.aspx?country=9/)) clinical risk factors considered in FRAX calculation.
Incorrect Answers:
Answer 1: T-score of -2.0 is not an indication for initiating treatment. Answers 2, 3, 5: Her FRAX score does not show a risk of hip or osteoporosis- related fracture high enough to be an indication for initiating treatment.

**A 32-year-old runner sustains a trimalleolar left ankle fracture. She undergoes open reduction and internal fixation and is kept non- weightbearing after surgery. At 2 months, what changes will occur in the articular cartilage of both her knees as a result of her current weightbearing regimen?**

1) Cartilage thickening in the left (ipsilateral) knee and no change in cartilage thickness in the right (contralateral) knee

2) Cartilage thinning in both knees

3) Cartilage thinning in the left (ipsilateral) knee and no change in cartilage thickness in the right (contralateral) knee

4) Cartilage thinning in the left (ipsilateral) knee and increased cartilage thickness in the right (contralateral) knee

5) Increased cartilage thickness in both knees
**
After a period of off-loading, the off-loaded limb will experience cartilage thinning. The contralateral limb will not demonstrate any cartilage changes.
Physiologic loading of cartilage increases proteoglycan synthesis and cell proliferation and is chondroprotective. Joint immobilization leads to cartilage thinning, tissue softening, and reduced proteoglycan content, leading to cartilage erosion. Joint overuse leads to cartilage damage (in vitro only).
Hinterwimmer et al. examined cartilage atrophy after partial load bearing
using quantitative MRI. They found cartilage thinning in all knee compartments (greatest thinning, medial tibia; least thinning, patella). There was no change in cartilage morphology in the contralateral knee.
Sun reviewed the relationship between mechanical loading and cartilage degeneration. In OA, cartilage breakdown occurs at the articular surface, and is then fueled by synovial proteases and cytokines. In RA, synovial cells and macrophages are the source of degradative enzymes and incite cartilage destruction.
Milward-Sadler et al. examined mRNA levels following mechanical stimulation in normal and osteoarthritic chondrocytes. Normal chondrocytes showed increased aggrecan mRNA and decreased matrix metalloproteinase 3 (MMP-3) mRNA after stimulation. This
chondroprotective response was absent in osteoarthritic chondrocytes.
Illustration A shows pro- and anti-inflammatory mechanisms of mechanical loading on chondrocytes. Underloading and overloading induce cartilage damage through pathways involving the upregulation of MMPs and ADAMTSs (ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs, or aggrecanase). Physiological loading blocks these increases.
Incorrect Answers:
Answer 1: Cartilage THINNING (not thickening) will occur on the offloaded limb (left). Answers 2 and 5: There will be a difference in cartilage thickness between knees as a result of different weightbearing status on both lower extremities. Answer 4: Noticeable cartilage hypertrophy does not occur on the uninjured limb.

**A morbidly obese 40-year-old man is scheduled to undergo hemilaminectomy for resection of an painful osteoid osteoma of the T6 lamina. He is positioned prone on a Jackson table and localization is performed with intraoperative fluoroscopy prior to the start of the case. At close to the end of the case, intraoperative frozen section reveals only normal bone fragment from the resected lamina. A probe is placed and a cross-table lateral radiograph reveals that the T7 lamina was resected instead of T6. At this point, the surgeon should**
**do all of the following EXCEPT**

1) Complete the surgery

2) Abort the case and obtain further imaging

3) Apologize to the patient and family

4) Formally document the error in the operative report

5) Inform the patient and family immediately after the operation
should include a disclosure of known facts and an explanation as to the likely cause, as well as ongoing treatment, follow up care, and prognosis.
The AAOS Information Statement about Wrong Site Surgery identifies 3 treatment steps following discovery of an error during surgery under general anesthesia: Return the patient to his preoperative condition, perform the correct procedure at the correct site, and advise the patient and family of what occurred and the likely consequences, if any, of the wrong- site surgery.
The AAOS Information Statement on Communicating Adverse Events states that the surgeon has an ethical and professional obligation to disclose the error to the patient and/or family. Disclosure should include what happened, why it happened, health implications, and what measures are being instituted to prevent recurrences.
Incorrect Answers:
Answer 1: Completion of the surgery at the correct site is necessary unless proceeding with the surgery at the correct site would increase the risk associated with extended operating time, or if correct-site surgery would result in an additional unacceptable disability.
Answers 3: Many patients have expressed that an apology is important. In the apology, the physician should express support for the patient and family, show compassion and concern, and acknowledge their emotional response and needs. This will help to set clear goals for the future patient-physician interaction.
Answer 4: Full disclosure is recommended and there should be no attempt at concealment or obfuscation. This is especially true for the operative report. Answer 5: A composed dialogue between the surgeon and both patient and family after the event is preferred to a hurried call from the operating room which is prone to misunderstanding and leaves no room for questions and answers.

**All of the following are Standards of Professionalism relating to interactions with industry for practicing orthopaedic surgeons EXCEPT:**

1) Decline gifts from industry with a market value over $100 (unless they are medical textbooks or patient educational materials)

2) Disclose to the patient any financial arrangements with industry that relates to the patient's treatment

3) Accept no direct financial inducements from industry for utilizing a particular implant

4) Disclose any relationship with industry to colleagues who may be influenced by your work

5) Decline to participate in industry sponsored non-CME courses or
conferences
**
The AAOS has adopted the Standards of Professionalism (SOP). These SOP’s establish mandatory, minimum levels of acceptable conduct for fellows and members of the AAOS to engage in relationships with industry. There are 17 standards with relation to industry. Answer choice 5 is not a SOP as surgeons are allowed to participate in or consult in meetings that are conducive to the effective exchange of information. The SOP also stipulate that tuition, travel, and modest hospitality (including meals and receptions) are allowed to attend an industry-sponsored non-CME course.

**A prospective randomized trial is conducted to test the efficacy of Vitamin C versus placebo in treating patients who develop chronic regional pain syndrome (CRPS) after distal radius fractures. At first follow-up, the rates of CRPS are 1% and 9% in the study and placebo group, respectively. Which statistical test is most appropriate to determine significance?**

1) Single factor analysis of variance

2) Chi-square test

3) Student t-test

4) Mann-Whitney rank sum test

5) Wilcoxon rank sum test
**
In the study provided, we need to determine whether distributions of categorical variables differ from one another. The appropriate study is the chi- square test.
Data can be classified as numerical (continuous) or categorical (proportional). Responses to such questions as "What is your major?" or Do you own a car?" are categorical because they yield data such as "biology" or "no." In contrast, responses to such questions as "How tall are you?" or "What is your G.P.A.?" are numerical. When comparing two independent means from numeric data, a t-test is performed. However, if categorical data is being compared, the chi- square test will determine if the proportions are really different.
Kocher et al. review basic clinical epidemiology and biostatistics relevant to orthopaedic surgery. Amongst other things, they describe that data can be summarized in terms of measures of central tendency, such as mean, median, and mode, and in terms of measures of dispersion, such as range, standard deviation, and percentiles.
Illustration A shows an algorithm for determining which test to use for varying data. Incorrect Answers:
Answer 1: Analysis of variance (ANOVA) is used to compare means of three or more independent groups in which the data are normally distributed.
Answer 3: Student t-test is used for comparing means of continuous data that is normally
distributed.
Answer 4: The Mann-Whitney and Wilcoxon rank sum tests are used for comparing means of non-continuous data.
Answer 5: The Mann-Whitney and Wilcoxon rank sum tests are used for comparing means of non-continuous data.

**A 35-year-old patient is involved in a motor vehicle accident and sustains multiple fractures including a closed comminuted proximal meta-diaphyseal tibia fracture. The surgeon is considering bridge plating the fracture using a minimally invasive approach. Which of the following is true regarding bridge plating?**

1) A locked plate construct (locked screws) or hybrid construct (locked and non- locked screws) is necessary.

2) Periosteal stripping is performed through two incisions proximal and distal to the fracture.

3) Bridge plating is performed following direct reduction of the fracture.

4) AO Type A diaphyseal fractures are best treated with this technique.

5) Bridge plating with a long working length creates a flexible, axially stable construct.
**
In bridged plating, only the most proximal and distal screw holes are filled. This creates a flexible, axially stable construct.
Bridge plating is applicable to all long-bone fractures with complex fragmentation and where intramedullary nailing or conventional plate fixation is not suitable. The construct preserves the blood supply to the fracture fragments as the fracture site is undisturbed during the operative procedure. It provides RELATIVE stability, allowing for some motion at the fracture site, leading to callus formation and secondary bone healing. The construct is FLEXIBLE because of increased distance between the 2 screws closest to the fracture (long working length), allowing for stress distribution and permitting more motion at the fracture site. The construct is also AXIALLY STABLE because the plate acts as an extramedullary splint and resists axial compression.
Livani et al. advocate using an anterior or antero-lateral approach for minimally invasive plating of the humerus. They recommend that distal access is obtained first, allowing identification of the lateral antebrachial cutaneous nerve. For distal fractures, they recommend extending the plate down to the lateral column.
Apivatthakakul et al. defined minimally-invasive plate osteosynthesis (MIPO) danger zones from the lateral epicondyle. They found the musculocutaneous nerve averaged 18- 43% of the humeral length, the danger zone for the radial nerve averaged 36-59% of the humeral length, and the most dangerous screws that penetrated or touched the radial nerve lay 47-53% of the humeral length.
Illustration A shows a distal tibia fracture. Illustration B shows radiographs 5 months after bridge plating of this fracture. There is callus formation, characteristic of indirect bone healing.
Answer 1: Locked plates are not necessary for bridge plating. Conventional plate/screws may be used.
Answer 2: Bridge plating through a minimally invasive approach avoids periosteal stripping and the plate lies in a submuscular location. It is especially important where comminution is present and preservation of tenuous
periosteal blood supply is critical.
Answer 3: Bridge plating is usually applied following some form of indirect reduction. Indirect reduction involves manipulating fragments into the correct position without opening the fracture site, thus minimizing damage to the blood supply. The main principle of indirect reduction is distraction.
Answer 4: AO Type A simple diaphyseal fractures are best treated with intramedullary nailing (relative stability) or anatomic reduction and compression plate fixation (absolute stability).

**Which of the following components of bone is most responsible for compressive strength?**

1) Type I collagen

2) Osteocalcin

3) Proteoglycans

4) Osteonectin

5) Osteopontin
**
Proteoglycans, in addition to calcium hydroxyapatite [Ca10(PO4)6(OH)2], are most responsible for providing compressive strength.
Bone is composed of both organic and inorganic components. Inorganic components include calcium hydroxyapatite and osteocalcium phosphate. Organic components include collagen, proteoglycans, matrix proteins, cytokines and growth factors. While Type I collagen is responsible for providing the tensile strength of bone, proteoglycans and calcium hydroxyapatite [Ca10(PO4)6(OH)2] are most responsible for providing compressive strength. Proteoglycans contain a core protein with various
numbers of covalently attached side chains of glycosaminoglycans. In addition to providing compressive strength, they are also responsible for binding growth factors and inhibiting mineralization.
Knothe et al. review the osteocyte. They discuss that osteocytes are the most abundant
cells in bone, are actively involved in maintaining the bony matrix, and may act as mechanosensors.
Illustration A shows a proteoglycan aggregate, which can form when individual molecules link onto a chain of hyaluronic acid.
Incorrect Answers:
Answer 1: Type I collagen is responsible for the tensile strength of bone. Answer 2: Osteocalcin is the most abundant non-collagenous protein in the matrix and promotes the mineralization and formation of bone.
Answer 4: Osteonectin is believed to have a role in regulating calcium or organizing mineral in matrix.
Answer 5: Osteopontin is a cell-binding protein.

**A prospective, randomized controlled trial of 150 patients undergoing total hip arthroplasty is performed to test whether repair of the capsule during a posterior approach reduces post-operative dislocations in the first three months. The study found no difference in dislocation rate if the capsule was repaired versus not repaired (p =**
**.34). Subsequently, a multicenter follow-up study of 2000 patients showed that repairing the capsule led to a decreased dislocation rate**
**in the first three months (p = .03). Assuming the second study reflects reality, which of the following errors occurred in the first study?**

1) Observer bias

2) Type-II error

3) Alpha error

4) Type-I error

5) Confounding error
**
In this situation, the null hypothesis was accepted when it should have been rejected.
This is a type-II error.
A study can have two types of errors. Type-I errors, or alpha errors, occur when the null hypothesis is rejected when it should have been accepted. The alpha level refers to the probability of a type-I error. By convention, the alpha level of significance is set at 0.05, which means that we accept the finding of a significant association if there is less than a one in twenty chance that the observed association was due to chance alone. Type-II errors, or beta errors, occur when the null hypothesis is accepted when it should be rejected. This
often occurs when studies are underpowered. In the example above, the null hypothesis is that repair of the capsule does not reduce dislocations within the first three months. Since the first study did not show a statistically significant difference, the null hypothesis was accepted. Since a more powered study showed that repair of the capsule does reduce dislocations, the null hypothesis should have been rejected in the initial study (if it was adequately powered).
Fosgate et al. review the importance of sample size calculations when performing research. They state that sample size ensures statistical significance if the subsequent data collection is perfectly consistent with the assumptions made for the sample size calculation (assuming power was set as
50% or greater).
Illustration A shows the difference between type-I and type-II errors. Video V is a lecture discussing statistical definition review of PPV, NPV, sensitivity and specificity.
Incorrect Answers:
Answer 1: Observer bias is when the observer (usually the investigator) influences the results of an experiment as a result of their own bias. Answer 3: Alpha errors are the same as type I error (see below).
Answer 4: A type-I error would reject the null hypothesis when it is true. Answer 5: A confounder is a variable that has associations with both the dependent and independent variables, potentially distorting their relationship. Confounders are not technically considered "errors," but instead are variables
that properly constructed studies attempt to avoid.

**Which of the following is a potential cause of fretting corrosion?**

1) The micromotion at the femoral head-neck junction in a modular total hip replacement

2) A stainless-steel cerclage wire is in contact with a titanium-alloy femoral stem

3) Friction between polyethylene liner and femoral head leading to osteolysis

4) The formation of pits within a stainless-steel plate and the subsequent release of metal ions

5) The formation of an adherent oxide coating on titanium implants
**
Micromotion at the femoral head-neck junction can lead to fretting corrosion, one of the most common causes of failure of a modular implant.
Modular components give surgeons excellent intraoperative flexibility, but are susceptible to various types of corrosion. While titanium and cobalt-chrome contain a protective surface oxide layer, continued micromotion at the modular junction may disrupt the protective layer leading to fretting corrosion, defined as micromotion at contact sites under load. This may eventually lead to a painful synovitis that necessitates a revision procedure.
Srinivasan et al. review modularity in total hip arthroplasty. Amongst other things, they discuss the modularity of the femoral head/neck junction, describing the morse taper interlocking system that provides both axial and rotational stability.
Illustration A shows an example of corrosion at the head/neck junction of a total hip arthroplasty.
Incorrect Answers:
Answer 2: This is an example of galvanic corrosion, as two dissimilar metals are in contact with each other.
Answer 3: This is an example of adhesive wear.
Answer 4: This is an example of pitting corrosion, or crevice corrosion. Answer 5: This process is called self-passivization, enabling titanium to become corrosion resistant.

**Which of the following situations is most likely to decrease sentinel event errors?**

1) Physician and nurse training is lengthened by 20%

2) Resident hours are decreased to 55 hours per week

3) An environment is created where all members of the healthcare team feel empowered to express their concerns and beliefs

4) Holding individuals responsible for errors in clinical judgement

5) Physicians and nurses are assigned to a smaller number of patients
**
Creating an environment where all members of the healthcare team feel empowered to express their beliefs increases communication, the key element in decreasing sentinel events.
Research has shown that 70% of sentinel event errors are caused by improper communication. Specific ways to improve communication include effective clinical handover between shifts and breaking down the "hierarchy" so that all members of the team can discuss their expectations and concerns. Barriers to effective communication include distractions, cultural differences, power distance relationships, time pressures, and lack of organization.
Leonard et al. describe specific clinical experiences in the application of surgical briefings, properties of high reliability perinatal care, the value of critical event training and simulation, and benefits of a standardised communication process in the care of patients transferred from hospitals to skilled nursing facilities. They recommend embedding standardized tools and behaviors to bridge differences in communications styles between clinicians.
Incorrect Answers:
Answer 1: Increasing training time is unlikely to decrease sentinel event errors if effective communication is not established.
Answer 2: Some studies have shown increased error rates with decreased resident physician work hours.
Answer 4: Holding individuals responsible for errors in clinical judgement has not specifically been cited as a way to decrease errors within a healthcare setting.
Answer 5: While this may decrease sentinel event errors, this has not been to be as effective as improvements in communication.

**Which of the following side effects is most strongly associated with the use of NSAIDs?**

1) Hepatic dysfunction

2) Renal impairment

3) Prolonged QTc

4) Seizures

5) Hematuria
**
All NSAIDs have the potential to cause serious renal impairment.
NSAIDs work by inhibiting the cyclooxygenase pathway (COX), which is comprised of the COX-1 and COX-2 pathways. The COX-1 pathway is involved in prostaglandin E2– mediated gastric mucosal protection and thromboxane effects on coagulation, while the COX-2 pathway is mainly involved with the modulation of pain and fever without effect on platelet function. While selective COX-2 inhibitors have a decreased side effect profile, all NSAIDS
have the potential to cause renal impairment and their use should be limited in patients with underlying renal disease.
Horlocker et al. review multimodal pain management in the perioperative setting of a total joint arthroplasty. Specifically, they note that NSAIDs should be used cautiously in patients with underlying renal dysfunction who are to undergo a procedure with major blood loss.
Griffin et al. reviewed 1,799 patients hospitalized for acute renal failure. They found that NSAIDs increased the risk of renal failure by 58% and that NSAID use resulted in 25 excess hospital admissions per 10,000 years of use.
Illustration A shows the COX pathways and their inhibition by NSAIDs. Incorrect Answers:
Answers 1, 3, 4, 5: NSAIDs have not been shown to be strongly associated with these side effects.

**It is recommended that invasive dental work be completed prior to the initiation of which of the following medications?**

1) Glucosamine

2) Cholecalciferol

3) Levothyroxine

4) Teriparatide

5) Bisphosphonates
**
Bisphosphonate therapy combined with invasive dental work increases the risk for development osteonecrosis of the jaw.
Bisphosphonates are a class of drugs that prevent bone mass loss by inhibiting osteoclast resorption. They are used in the treatment of vertebral compression fractures, non- vertebral fragility fractures, osteogenesis imperfecta, multiple myeloma, and avascular necrosis. Because bisphosphonates have been associated with osteonecrosis of the jaw, it is suggested that all invasive
dental work be completed prior to initiation of treatment.
Pazianas et al. (2011) review the safety profile of bisphosphonates. Specifically, they cite gastrointestinal discomfort, atypical femur fractures, osteonecrosis of the jaw, ocular inflammation, and musculoskeletal pain as common side effects. They state there is limited evidence surrounding
bisphosphonate's association with esophageal cancer and atrial fibrillation.
Pazianas et al. (2007) reviewed 11 publications that reported 26 cases of osteonecrosis of the jaw following initiation of bisphosphonate treatment. Age
>60 years, female sex, and previous invasive dental treatment were the most common characteristics of those who developed ONJ.
Illustration A shows the various bisphosphonates and their mechanisms of action. Illustration B shows an example of osteonecrosis of the jaw, a side effect that has been linked to bisphonphonate treatment.
Incorrect Answers:
Answer 1: Glucosamine is a dietary supplement used in the management of osteoarthritis. It is not contraindicated prior to dental work.
Answer 2: Cholecalciferol is Vitamin D3. Toxicity and side effects are rare with Vitamin D therapy.
Answer 3: Levothyroxine is used in the treatment of hypothyroidism. It is not contraindicated prior to dental work.
Answer 4: Teriparatide (Forteo) has been used in the treatment of osteonecrosis of the jaw caused by bisphosphonates.

**Figures A and B show radiographs of a 24-year-old female with a soccer injury. A physical examination reveals an isolated, closed injury with no clinical features of neurovascular injury or compartment syndrome. She has been consented to be treated with intramedullary nail fixation. A pre-operative note by the anaesthesiology team makes reference to the patients fair skin and natural red-hair color. How will this information affect the post-operative management of this patient?**
1) Longer duration of anticoagulation due to increased risk of DVT

2) Avoiding anticoagulation medications due to increased risk of bleeding

3) Require higher dosages of post-operative analgesia

4) Longer period of non-weight bearing on surgical limb

5) Avoiding opioids due to higher risk of unrecognized allergies
**
Female patients with natural red-hair may require higher dosages of post- operative analgesia compared to other hair types.
Melanocortin-1-receptor (MC1R) is one of the key proteins involved in hair color and skin tone. Mutations of the MC1R alleles can render this protein non- functional, which results in a phenotype of red-hair and fair skin. Mutations of the MC1R have shown to modulate the pain response and opioid efficacy in these patients. Women are more commonly affected and often require more anaesthetic and higher dosages of opioid to achieve comparable MAC level and pain-relief, respectively, as women with other hair types.
Liem et al. showed that a greater concentration of induction and maintenance agents (sevoflurane and desflurane, respectively) were required to sustain comparable MAC levels in red-haired patients as dark haired patients.
Fillingim et al. reviewed the affect of gender, sex and pain. They concluded there is a biopsychosocial element of pain that is perceived differently by men and women. In terms of postoperative and procedural pain, the outcome might be more severe in women than men.
Delaney et al. looked at the involvement of the melanocortin-1 receptor in acute pain in mice. They found that while the MC1R is better known as a gene involved in mammalian hair colour, it was shown to be involved in the pain pathway of inflammatory but not neuropathic origin. Mutations of MC1R showed increased tolerance to noxious pain stimulus in mice.
Figures A and B are AP and lateral radiographs of a left tibia. There is a low energy, distal third shaft fracture with no cortical apposition on the AP view.
Incorrect Answers:
Answer 1,2: Mutations in the Melanocortin-1-receptor (MC1R) has not shown to affect the coagulation pathway, with no increased risk of bleeding or clotting.
Answer 4: Mutations in the Melanocortin-1-receptor (MC1R) does not affect fracture fixation or weight-bearing status post-operatively
Answer 5: There is not a higher risk of opioid allergy in these patients.

**Which of the following medications used for thromboprophylaxis following orthoapedic surgery is a direct inhibitor of factor Xa?**

1) Dextran

2) Rivaroxaban (Xarelto)

3) Coumadin

4) Fondaparinux (Arixtra)

5) Aspirin
**
Rivaroxaban (Xarelto), an oral anticoagulant, is a direct inhibitor of factor Xa.
Rivaroxaban (Xarelto) is a member of a new class of oral, direct (antithrombin- independent) factor Xa inhibitors, which restrict thrombin generation both in vitro and in vivo. Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi.
Eriksson et al. compare rivaroxaban to enoxaparin for the prevention of symptomatic venous embolism following total hip arthroplasty. Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group. Additionally, major bleeding events were similar between the two groups.
Illustration A shows the mechanisms of action of various agents used for thromboprophylaxis.
Incorrect Answers:
Answer 1: The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing their electronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function.
Answer 3: Coumadin inhibits vitamin K 2,3-epoxide reductase, thereby limiting the production of vitamin K-dependent clotting factors (II, VII, IX, X) as well
as Protein C and Protein S.
Answer 4: Fondaparinux is an indirect inhibitor of factor Xa, not direct.
Answer 5: Aspirin inhibits the production of prostaglandins and thromboxanes.

**The origin of bovine derived grafts is particularly important to which of the following religious groups?**

1) Christianity

2) Islam

3) Hinduism

4) Buddhism

5) Judaism
**
The origin of bovine-derived surgical implants should be discussed in further detail with patients ascribing to Hinduism.
Patients come from a variety of religious backgrounds. Depending on a patient’s religion, the origin of surgical implants may have implications for their use. In Hinduism, bovine animals are considered sacred. Use of cow by- products is considered purifying in nature. Subsequently, the origin of bovine derived implants should be discussed with patients ascribing to Hinduism.
Easterbrook et al. evaluated the utility of porcine and bovine surgical implants amongst those of Jewish, Muslim and Hindu faiths. Hindu religious leaders, who were surveyed, did not approve of the use of bovine surgical implants.
Enoch et al. evaluated the acceptability of biological products amongst various religious groups. The Hindu religious leaders were found to not have an objection to the use of biological implants derived from cows.
Illustration A shows a clinical photo of a fetal bovine derived dermal substitute. Incorrect Answers:
Answers 1, 2, 4, 5: While the origin of implants should be discussed with all patients prior to use, bovine derived implants may have specific implications with Hindu patients. Use of porcine-implants should be discussed with patients who are of Jewish and Muslim faiths.

**Immunological testing of anti-cyclic citrullinated peptide antibodies (anti- CCP) is most commonly used for the diagnosis and prognosis of which immunological condition?**

1) Ankylosis spondylitis

2) Rheumatoid arthritis

3) Psoriatic arthritis

4) Systemic lupus erythematosus

5) Reiter's syndrome
**
Anti-cyclic citrullinated peptide antibodies (anti-CCP) are commonly used as a marker for the diagnosis and prognosis of rheumatoid arthritis (RA).
Immunological studies are commonly performed to investigate cases of suspected rheumatoid arthritis. Rheumatoid factor has historically been used as a primary marker for RA. However, in more recent years, the use of anti- CCP antibodies has shown to be as sensitive as, and more specific than, rheumatoid factor (RF) in early and fully established disease. In general, anti-
CCP assays equate to a sensitivity of 50-75% and a specificity of 90-95%. High levels of anti-CCP have been shown to be indicative of a more erosive disease process and may be detected before the onset of arthritis.
Gardner and Kadel reviewed the laboratory studies most commonly used in rhuematologic diseases. Standard ordering for clinically suspected RA include Rf, anti- CCP, ESR/CRP as well as other markers of autoimmune diseases such as antinuclear antibodies, anticardiolipin antibodies and lupus anticoagulant, HLA-B27, and uric acid levels.
Illustration A shows the sensitivity and specificity of anti-CCP vs. RF in a variety of autoimmune diseases.
Incorrect Answers:
Answers 1,3-5: Anti-CCP is not routinely used to diagnose and monitor these conditions.

**Vitamin C has been shown to decrease the likelihood of which of the following complications following surgery on the foot and ankle in non-diabetic patients?**

1) Nonunion

2) Complex Regional Pain Syndrome, type II

3) Malunion

4) Complex Regional Pain Syndrome, type I

5) Wound infection
**
Vitamin C has been shown to decrease the likelihood of developing complex regional pain syndrome (CRPS), type 1, when given post-operatively to patients undergoing foot and ankle and wrist surgery.
CRPS is a frequent post-operative complication, with rates varying from 10-
37%. Type I CRPS does not have an identifiable nerve lesion, while type II has an identifiable nerve lesion. Multiple studies have shown that vitamin C decreases rates of CRPS following distal radius fractures, and more recently, the same has been shown following foot and ankle surgery. While the exact mechanism of CRPS is unknown, vitamin C has been shown to reduce lipid peroxidation, scavenge hydroxyl radicals, protect the capillary endothelium, and inhibit vascular permeability. All of these characteristics of vitamin C may play a role in modulating the pain pathway.
Zollinger et al. perform a double-blind, prospective, multicenter trial where
416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The prevalence of complex regional pain syndrome was 2.4% in the vitamin C group and 10.1% in the placebo group.
Besse et al. compare two groups of patients undergoing surgery on the foot and ankle to determine the effect of vitamin C on the development of CRPS, type I. CRPS type I occurred in 18 cases (9.6%) in the group not given vitamin C, and 4 cases (1.7%) in the group given vitamin C.
Illustration A shows an example of a limb affected by CRPS. Note the increased swelling, a common physical exam finding in patients afflicted with the disease.
Incorrect Answers:
Answers 1, 2, 3, 5: Vitamin C has not been shown to decrease the incidence of these conditions.

**A 25-year-old Spanish speaking male presents to the emergency department 6 hours after sustaining the injury seen in Figure A. He is grossly intoxicated and screaming in pain. Physical examination reveals a closed injury with overlying muscular compartments that are extremely firm to palpation. After sedating the patient, measurements of the intracompartmental pressures were all found to be**
**> 75mmHg. His wife is Spanish speaking and expected to arrive to the hospital in 2-3 hours with a relative to help with translation. No medical translator is**
**available. You attempt to outline the risk and benefits of surgery to the patient, but the he repeatedly interrupts you and yells out ,"No surgery!". An English-Spanish speaking friend is with the patient and says that he has known the patient for over 2 years and will help with any decision making. What would be the next most appropriate step in the management of this patient?**
1) Delay surgery to monitor the patient for impending compartment syndrome

2) Proceed with surgery with urgent fasciotomy after documenting the necessity of treatment without consent

3) Delay the surgery until the wife arrives and able to give informed consent with the aid of a translator

4) Proceed with surgery for urgent fasciotomy after obtaining informed consent from the patients friend

5) Respect the patients autonomy and reassess the patient in the morning when he demonstrates capacity to accurately comprehend the proposed treatment
**
This patient is presenting with compartment syndrome of the right tibia. In a situation of required surgery for limb threatening injury without available legal consent the surgeon should confirm and document the necessity of care with a fellow colleague.
Physicians are responsible for whether a patient is able to reasonably understand their medical condition and the nature of any proposed medical procedure, including the risks, benefits, and available alternatives. If the patient lacks this capacity, disclosure imposed by the doctrine of informed
consent are excused because irreparable harm that may result from the physician’s hesitation to provide treatment. Detailed documentation is also important. In addition, the attending physician should contact the Risk Management Dept at the hospital for support prior to surgical intervention or have a medical translator involved to ensure information is being translated properly.
Katz et al. reviewed the medical decision making process of Hispanic people. They showed that Hispanic people are more likely to permit their physician to take the predominant role in making health decisions compared to Non- Hispanic people.
Figure A shows a comminuted tibia and fibula fracture. Incorrect Answers
Answer 1: This patient has confirmed compartmental syndrome. Surgical delay would be negligent.
Answer 3: Delay until his wife arrives would be necessary in non-life or-limb threatening conditions. In this case however, surgical delay could result in significant harm to the patient and therefore, the doctrine of informed consent can be excused.
Answer 4: Consent can only be given by a friend that has pre-existing notice of the patients views in the setting of emergencies and only when the dedicated decision maker is not available. The patients friend does not have enduring power of attorney and has not been appointed as a formal substitute decision-maker.
Answer 5: The patient does not demonstrate capacity to make an informed decision about his health. Therefore the views of his autonomy cannot be formulated.

**A Spanish speaking child sustained the injury seen in Figure A after a fall at school. He was casted in the emergency department without the assistance of an interpreter and advised to return to see an orthopaedic surgeon in 1 week. However, the family returns to the emergency department with the child 3 months later, still in the cast. What is the most likely reason the child did not attend the recommended orthopaedic follow-up visit.?**
1) The child is a victim of neglect

2) The child had no symptoms of pain

3) He was allowed to return to school wearing the cast

4) Concerns of cost

5) Follow-up instructions were not effectively communicated
**
The most likely reason the child did not attend the recommended orthopaedic follow-up visit was a language barrier preventing effective communication of the intended follow-up instructions.
Communication skills and cultural competence is a key element in good orthopaedic care. Poor communication can often lead to devastating outcomes. In this example, poor communication resulted in this patient being lost to
follow-up. Language barriers must be accommodated and alternative methods of communication must be utilized.
Levinson et al. examined how patients present their medical issues in clinical encounters and how physicians respond to these clues in routine primary care and surgical settings. They showed that good communication relies mostly on the physicians ability to identify patient clues within the clinical encounter.
Poor communication between the physician tended to delay clinical visits, poor follow-up and unsatisfactory outcomes.
Figure A is an AP radiograph of the elbow in a skeletally immature patient. Figure B is a lateral radiograph of the elbow with a posterior fat pad sign, suggestive of an occult fracture.
Incorrect Answers:
Answer 1,2,3,4: The most likely reason for loss to follow-up in this scenario is miscommunication regarding follow-up.

**A 25-year-old female presents to the emergency room within increasing left shoulder pain after walking into a door 5 months ago. She previously sustained a femoral fracture 2 years ago after tripping on a rug. Relevant skeletal survey radiographs and tissue biopsy results are shown in Figures A through D. Laboratory investigations show normal glomerular filtration rate and creatinine clearance. Dual energy x-ray absorptiometry (DEXA) scan shows T-score of -1.4 and**
**-1.2 at the hip and lumbar spine, respectively. Which of the following laboratory values in Figure E most likely reflects this patient's condition?**
1) A

2) B

3) C

4) D

5) E
**
This patient has primary hyperparathyroidism. Laboratory investigations are likely to show elevated serum intact parathyroid hormone (PTH), alkaline phosphatase (ALP) and ionized serum calcium, and low serum phosphate.
Primary hyperparathyroidism is most commonly caused by a single adenoma (80-90%). Besides the signs and symptoms of hypercalcemia, patients present
with calcification of menisci and articular cartilage, erosions in hand bones, "salt and pepper skull", and brown tumors (osteoclastomas), which appear as lytic regions expanding the cortex and causing pathological fractures, so named because of hemosiderin deposition.
Singhal et al. reviewed primary hyperparathyroidism. They advocate routine serum calcium levels for patients with pathologic fractures. If this is elevated, total and ionized calcium and intact PTH levels should be obtained. They feel that surgery for orthopaedic stabilization and parathyroidectomy should be performed simultaneously for better outcome.
Mankin et al. reviewed metabolic bone disease. They suggest that patients with mild disease with normal calcium levels do not require treatment. For patients with high calcium levels, treatment should include maintenance of fluid balance, localization and removal of the adenoma, bony stabilization, and medications (calcitonin, estrogen, bisphosphonates, and calcimimetics such as cinacalcet).
Figure A is an AP radiograph showing a lytic expansile lesion with pathological fracture in metadiaphyseal region of left humerus with similar lesion in the
fifth posterior rib. Figure B is an AP radiograph showing a lytic expansile lesion in the third metacarpal of the right hand and the fifth metacarpal of the left hand. Figure C is a low power micrograph of a brown tumor demonstrating a central zone of bone resorption, and filling with fibroblastic tissue, with a peripheral rim of osteoid production. Figure D is a high power micrograph of a brown tumor. In areas of bone resorption, there are numerous osteoclast-like giant cells amidst a fibrous stroma. This is unlike a true giant cell tumor, which lacks a fibrogenic stroma.
Incorrect Answers:
Answer 2: Elevated PTH and ALP, and low serum calcium and high serum phosphate are characteristic of secondary hyperparathyroidism. This occurs in chronic renal disease, where there is overproduction of PTH because of hyperphosphatemia, hypocalcemia,
and impaired 1,25-dihydroxyvitamin D production by the diseased kidneys. This patient has normal renal function. Answer 3: Elevated PTH, ALP, serum calcium and phosphate occur in tertiary hyperparathyroidism. This again occurs in chronic renal disease after prolonged chronic secondary hyperparathyroidism or after renal transplantation, where the parathyroid glands become autonomous and PTH levels do not normalize. This patient has normal renal function.
Answer 4: Normal PTH, low ALP and high serum calcium and phosphate occur in hypophosphatasia. The defect lies in tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and urine phosphoethanolamine levels are
elevated.
Answer 5: Low PTH, normal ALP, low serum calcium and high serum phosphate levels suggest hypoparathyroidism.

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