1. General Principles & Basic Science MCQs

DISCUSSION: The main function of collagen in articular cartilage is to provide the tissue’s tensile strength.  It also immobilizes proteoglycans within the extracellular matrix.  Compressive properties are maintained by proteoglycans.  Cartilage metabolism is maintained by the indwelling chondrocytes.  The flow of water through the tissue promotes transport of nutrients and provides a source of lubricant for the joint.REFERENCES: Simon SR (ed): Orthopaedic Basic Science.  Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 3-44.Mow VC, Ratcliffe A: Structure and function of articular cartilage and meniscus, in Mow VC, Hayes WC (eds): Basic Orthopaedic Biomechanics, ed 2.  Philadelphia, PA, Lippincott-Raven, 1997, pp 113-177.

A funnel plot is the most commonly used statistical test for detection of publication bias in meta-analyses.Publication bias occurs because studies with a non-significant result, so-callednegative studies, have a higher likelihood of being rejected than positive studies, and are oftentimes not even submitted for publication. Funnel plots, which plot the effect size of a study against a measure of the study’s size are used to detect this bias. This method is based on the fact that larger studies have smaller variability, whereas small studies, which are more numerous, have larger variability. Thus the plot of a sample of studies without publication bias will produce a symmetrical, inverted-funnel shaped scatter, whereas a biased sample will result in a skewed plot.Vavken et al. reviewed orthopaedic meta-analyses in order to determine whether publication bias was assessed and to evaluate its effect on the outcomes of these meta-analyses. They found that only 35% of all orthopaedic meta-analyses published between 1992 and 2008 in English and German assessed publication bias. Adjustment for publication bias did not produce significantly different results, but the magnitude of the pooled estimates in the affected meta-analyses changed by 29% on average.Illustration A depicts a symmetrical funnel plot with no evidence for publication bias. Illustration B shows a skewed funnel plot suggesting publication bias, as it is missing studies in the lower left corner, i.e. ‘‘negative studies’’. Illustration C depicts a forest plot comparing the incidence of squeaking between ceramic-on-ceramic (COC) and ceramic-on-polyethylene (COP). Illustration D is an example of a ROC curve examining the probability of DVT.Incorrect Answers:

DISCUSSION: The MRI scan shows near complete involvement of the femoral head with bone marrow changes and some collapse of the necrotic segment.  This is most suggestive of osteonecrosis.REFERENCE: Urbaniak JR, Jones JP Jr (eds): Osteonecrosis: Etiology, Diagnosis, and Treatment.  Rosemont, IL, American Academy of Orthopaedic Surgeons, 1997.

Although previous theories on acetabuIar wear implicated fatigue cracking and delamination which is a major mode of polywear in knees, the primary mechanism of wear of polyethylene acetabular components has been shown to be adhesion and abrasion. In an analysis of 128 componenets retrieved at autopsy or revision surgery, wear appeared to occur mostly at the surface of the components and to be due to large strain plastic deformation and orientation of the surface layers into fibrils that subsequently ruptured during multidirectional motion. It was also shown conclusively that 32 mm displayed significantly more wear (volumetric wear) than with either 22 or 26/28 mm heads ( 1 mm increase in size increased volumetric wear by 10%). The wear at the articulating surface was characterized by highly worn polished areas superiorly and less worn areas inferiorly separated by a ridge. Abrasion was very common, occurring after adhesion and plastic deformation of poly fibrils, and abrasion secondary to third body wear. As well, wear rates decreased with longer survival of components, indicating a "wearing in" phenomenon, arguing against oxidative and fatigue wear. Crevice corrossion = occurs in fatigue cracks with low 02 tension (under screw heads,etc.) Oscillatorry fretting = cyclical outer surface abrading from small movements. Fatigue and delamination = predominant in total knees, where stresses are maximum just below the surface of the poly, causing fatigue over time with susequent delamination. In contrast, hip wear occurs primarily at the surface of the poly.

Posterolateral disk herniations will generally compress the transversing nerve root. Therefore, a posterolateral disk herniation at the L4-5 level will typically compromise the L5 nerve root. Far lateral (extraforaminal) disk herniations generally compromise the exiting nerve root. Therefore, an extraforaminal herniation at the L4-5 level will typically compromise the exiting L4 nerve root.

Gabapentin acts by inhibiting presynaptic calcium channels, thus preventing the release of neurotransmitters.Gabapentin (also known as Neurontin) is a medication that is commonly used to treat neuropathic pain. It acts by binding the alpha2delta subunit of voltage-dependent calcium channels on the presynaptic membrane. This serves to increase GABA synthesis, as well as inhibit the release of excitatory neurotransmitters. These neurotransmitters are believed to be part of the pathway leading to neuropathic pain.Bennett et al. provide a review of the pharmacology of gabapentin for the use of neuropathic pain. They note effective antihyperalgesic and antiallodynic properties of gabapentin but not significant anti-nociceptive action. Among patients with neuropathic pain they found an average pain score reduction of 2.05 points on an 11 point Likert scale, which compared favorably to placebo.Mehta et al. explored outcomes of gabapentin and pregabalin (Lyrica) for use in patients with spinal cord injury. Both agents were found to decrease pain and secondary conditions such as sleep disturbance. They did not directly compare these agents to other analgesic medications.Guy et al. present a meta-analysis of the use of anticonvulsants (such as gabapentin) to treat pain in patients with spinal cord injury. Large effect size was seen in 4 of 6 studies looking at the effectiveness of gabapentin.Illustration A show the mechanism of currently available antiepileptic drugs (AEDs) that target several molecules at the excitatory synapse. Gabapentin and pregabalin bind to the a2d subunit of voltage-gated Ca2+ channels, which is thought to be associated with a decrease in neurotransmitter release.Incorrect Answers

DISCUSSION: Pacinian corpuscles are nerve endings that provide the perception of pressure.REFERENCE: Sunderland SS: Nerves and Nerve Injuries, ed 2.  New York, NY, Churchill Livingstone, 1978, pp 343-347.

Osteoconductive bone graft material is described as the scaffold that allows new bone growth. This new bone is created via sprouting capillaries, perivascular tissue, and osteoprogenitor cells on the three-dimensional graft structure, permitting creepingsubstitution, which allows for graft incorporation. An osteoinductive graft will stimulate the recruitment of progenitor cells that can differentiate into osteoblastic cells. Specific BMPs are osteoinductive. Osteogenic material contains viable cells with the ability to form bone. The ability to provide osteoprogenitor cells is only seen in fresh autograft. Other grafts rely on the recruitment of host progenitor cells to differentiate.

The extracellular matrix consists of water, proteoglycans, and collagen. Water makes up the majority (approximately 65% to 80%) of wet weight; 95% of the collage is type II with much smaller amounts of other collagens, including types IV, VI, IX, X, and XI. The exact functions of these other collagens are unknown, but they are believed to be important in matrix attachment and stabilization of the diameter of collagen fibrils.

Gamma irradiation of Ultrahigh Molecular Weight Polyethylene leads to free oxidation with resultant breaking of polymer chains, changes in the crystalline structure, and deterioration of the mechanical properties of the polymer. Fracture toughness, fatigue strength, and mechanical strength all decrease while the wear rate of irradiated UHMWPE increases. Stiffness is another matter. Initially after irradiation, crosslinking and stiffness actually increase, but in the long term stiffness will decrease as crosslinks continue to break secondary to irradiation induced oxidative damage.

Articular cartilage in the knee adapts to exercise by increasing the glycosaminoglycan (GAG) content. Increased GAG content is important to cartilage health. There is a higher glycosaminoglycan content in the lateral femoral cartilage compared to the medial femoral cartilage. Using T1 gadolinium enhanced MRI, the GAG content is seen to be increased in moderate distance runners. Moderate exercise may be a good treatment, not only to improve joint symptoms and function, but also to improve the knee cartilage GAG content in patients at high risk of developing osteoarthritis.

Fixation of pelvic and acetabular fractures in pregnancy is not contraindicated. However, both maternal and fetal morbidity and mortality is increased in this patient subset. Factors shown to be associated with increased fetal mortality include: injury severity, mechanism of injury, and maternal hemorrhage. Surgical approach, fracture classification, fetal position, and the trimester of pregnancy have not been shown to affect fetal morbidity or mortality.

The structure shown is the exiting nerve root at the L3-4 disk, which is the right L3 root.

The Mann-Whitney U test is used when data are nonparametric, meaning either not normally distributed or variances are not equal among groups. Both the Student t test and ANOVA are used with parametric, normally distributed data. A regression analysis is a statistical model that allows for control of potentially confounding variables. It is used to assess the relationship between a dependent variable and (usually) multiple independent variables.

When an implant is loaded below the yield point, by definition, it undergoes elastic deformation, meaning that all of the deformation recovers when the load is removed. If it is loaded above the yield point, then plastic or permanent deformation occurs. Fatigue is the gradual accumulation and progression of cracks in the material, which, after many cycles of loading, can lead to gross failure. Creep is the gradual accumulation of permanent (plastic) deformation over time, which may occur with polymeric materials but is not typical of metals or ceramics. Torsion refers to a torque being applied about the long axis of a bone or an implant. In general, the materials and dimensions of an implant are chosen to avoid plastic deformation or fatigue failure during typical clinical use.

Whereas all of the factors will have an impact on frame rigidity and stability, the single biggest factor is the pin diameter because it has an exponential effect.Which of the following clinical scenarios represents the strongest indication for locked plating technique in a 70-year-old woman?Segmentally comminuted ulnar fractureSimple diaphyseal fracture of the humerusTransverse midshaft displaced clavicle fracturePeriprosthetic femur fracture distal to a well-fixed total hip arthroplastySchatzker 2 fracture of the tibia with severe joint depression and comminutionLocking screw fixation is a relatively new option in the armamentarium of orthopaedic surgeons treating fractures. The understanding of the biomechanics, implications to healing, and optimal indications and surgical techniques is still in evolution. A periprosthetic proximal femur fracture with a stable prosthesis is best treated with open reduction and internal fixation with locking proximal fixation with or without cerclage cables. Diaphyseal fractures treated with compression plating or bridge plating can be treated well with conventional implants unless osteoporosis is severe. An AO/OTA B-type partial articular fracture is also better suited to standard buttress plating with periarticular rafting lag screws. Locking fixation is not always required for a transverse displaced midshaft clavicle fracture.What is the post-amplification product of reverse transcription polymerase chain reaction (RT-PCR)?RNADNAProteinMitochondriaImmunoglobulinsReverse transcription polymerase chain reaction (RT-PCR) is a variant of polymerase chain reaction (PCR) used in molecular biology to generate many copies of a DNA sequence from fragments of RNA. The RNA strand is first reverse transcribed into its DNA complement, followed by amplification of the resulting DNA using polymerase chain reaction. Polymerase chain reaction amplifies short segments of DNA by using the temperature stable DNA polymerase enzyme.A 63-year-old woman falls from standing and lands on her right hand. She complains of deformity and wrist pain. Radiographs are provided in Figure A. Following closed reduction, the patient inquires whether she has osteoporosis and if she is likely to have another fracture. In counselling the patient, which of the following is the strongest predictor for a future fracture from low energy trauma?Bone mineral density T-score < -2.5Low vitamin D levelsFamily history of osteoporosisHistory of a prior fragility fractureTen year history of oral prednisone useEach of the answer choices is a risk factor for subsequent fragility fracture, but patient history of a prior fragility fracture is the strongest predictor.Bouxsein et al reviews the proper care, diagnosis, and prevention of fragility fractures. History of a fragility fracture is the greatest predictor of a future fracture from low energy trauma. Appropriate care includes not only treatment of the fracture itself, but also proper evaluation to identify the etiology of the fracture and appropriate intervention to rectify the underlying pathology. Evaluation includes bone densitometry, lab testing of Vitamin D and calcium.A T-score compares your bone density to the optimal peak bone density for your gender. It is reported as number of standard deviations below the average. A T-score of -1 to -2.5 is considered osteopenia, and a risk for developing osteoporosis. A T- score of less than -2.5 is diagnostic of osteoporosis.Long-term alendronate (Fosamax) use for osteoporosis has been associatedwith which of the following?ScurvyDetached retinaUterine carcinomaOsteonecrosis of the femoral headDiaphyseal femoral insufficiency fracturesAlendronate is a bisphosphonate that inhibits the ruffled border of the osteoclast. When used long term, this class of medication prevents the normal bone remodeling process. Long-term use has recently been shown to be associated with insufficiency fractures of the femur. Osteonecrosis of the jaw has been described but not in other anatomic locations. Scurvy occurs because of a lack of vitamin C and use of bisphosphonates is not associated withuterine cancer or a detached retina.Implants composed of polylactic acid are excreted by what system after they are absorbed?HepaticRenalRespiratoryGastrointestinalPolylactic acid suture and suture anchors are popular bioabsorbable orthopaedic implants. This material undergoes hydrolysis of the ester background in vivo. Resulting lactic acid enters the tricarboxylic acid (Krebs)cycle and is excreted as carbon dioxide by the lungs. Polyglycolic acid and poly(p- dioxanone) may also be excreted by the kidneys.A patient sustains a grade III medial collateral ligament injury. One year later, when compared to collagen in an uninjured ligament, an increase is likely in thegross number of fibers.proportion of type III fibers.cross-linking.mass and diameter of fibers.Studies on animal models have shown that there is a change in collagen fiber type and distribution early in the healing process. There is a higher portion of type III fibers than innormal ligament initially, but this ratio returns to normal about 1 year after the injury occurs. Healing ligaments show an increased number of collagen fibers, but the number of mature collagen cross-links is45% of predicted value after 1 year. There is also a decrease in the mass and diameter of the collagen fibers.Sclerostin and dickkopf-1 (Dkk-1) are direct inhibitors of what pathway related to bone and/or cartilage regulation?Bone morphogenetic protein (BMP)/SMAD pathwayReceptor activator of nuclear factor kappa beta (RANK)/RANK ligand (RANKL) pathwayWnt/Beta-catenin (ß-catenin) pathwayParathyroid hormone (PTH) pathwayDkk-1 and sclerostin are proteins that inhibit the binding of the Wnt molecule to receptors LRP5/6. In the absence of sclerostin and Dkk-1, Wnt binds to its receptor, which in turn inhibits phosphorylation of the ß-catenin. The unphosphorylated ß-catenin then builds up in the cytoplasm of the cell, allowing it to be transported to the nucleus of the cell. Once in the nucleus, ß- catenin will lead to upregulation of a series of proteins involved in osteoblast formation differentiation. Knocking out or inhibiting sclerostin or Dkk-1 results  in increased bone mass secondary to constitutive activation of the Wnt/ß- catenin pathway. The other responses are not directly affected by Dkk-1 or sclerostin. RANKL and RANK are expressed on osteoblasts and osteoclasts, respectively, and are involved in osteoblast-mediated osteoclast activation. BMPs work through SMADs to cause osteoblastic differentiation, and there is reported crosstalk between the Wnt and BMP pathways (but this is an indirect link). Finally, PTH at physiologic levels binds to osteoblasts, causing a series of events that lead to osteoblast-mediated osteoclast activation and subsequent increased bone resorption.During endochondral ossification of the growth plate, the process that most contributes to the longitudinal growth of long bones ischondrocyte apoptosis.chondrocyte hypertrophy.chondrocyte proliferation.growth plate matrix synthesis.The growth plate is divided into 5 distinct zones: reserve, proliferative, maturation, hypertrophy, and vascular invasion. During growth-plate chondrocyte hypertrophy, intracellular volume and an increase in chondrocyte height are responsible for most growth of long bones. Other factors that contribute to bone growth are chondrocyte proliferation and matrix synthesis, but to a lesser degree than chondrocyte hypertrophy. Growth plate chondrocytes undergo programmed cell death (apoptosis) after hypertrophytakes place.Bacterial resistance to tetracycline is confirmed by ribosome protection, tetracycline modification, andaltered RNA polymerase.altered membrane binding protein.increased drug efflux.DNA gyrase mutation.Mutations of bacterial DNA gyrase can decrease the effectiveness of quinolones. Altered membrane-binding protein is observed with resistance to ?-lactam antibiotics. Tetracyclines are antibiotics that inhibit bacterial growth by stopping protein synthesis. Three specific mechanisms of tetracyclineresistance have been identified: increased tetracycline efflux, ribosome protection, and tetracycline modification. Alteration of RNA polymerase is found in resistance to rifampin.A 14-year-old boy has failed physical therapy management for Scheuermann kyphosis, and an extension thoracolumbosacral orthosis brace is recommended. The boy and his parents are told that the brace will force his thoracic spine into normal sagittal alignment and put the anterior vertebral bodies of the thoracic segment into tension, which will induce bone growth and normalization of wedge- shapedvertebrae. What name is associated with this process?Hooke's lawKirchhoff's lawWolff's lawHeuter-Volkmann principleThe Heuter-Volkmann principle shows that bone placed in longitudinal tension will tend to stimulate longitudinal growth, and that compressive longitudinal forces inhibit longitudinal growth, making this response the best choice. Hooke's law relates to stress being proportional to strain and is not directly related to bone growth. Kirchhoff's laws apply to electrical circuit design. Wolff's law states that bone remodels in response to mechanical stress, with the correlate that increased stress causes increased growth, and decreased stress leads to bone loss.A tendon repair is thought to be weakest during which phase of tendon healing?InflammatoryProliferationMaturationRemodelingHealing after a tendon repair or rupture has the following stages: inflammatory, cellular proliferation, and remodeling. During the inflammatory phase, neutrophils and macrophages migrate into the injury site and release chemotactic factors that recruit fibroblasts. A tendon is thought to be weakest5 to 21 days after repair, which coincides with the inflammatory phase. During the proliferative phase, inflammatory cells secrete cytokines and growthfactors (platelet-derived growth factor, insulin-like growth factor, bone morphogenetic protein (BMP)-12 and BMP 13, and transforming growth factor- beta) that promote differentiation of fibroblasts. Fibrosis and decreased cellularity are the hallmarks of the remodeling stage.A 4-year-old boy has bilateral genu varum and is in the fifth percentile for height for his age. A younger sister has less severe genu varum. Radiographs reveal physeal cupping and widening on both the distal femur and proximal tibia. Laboratory studies show sodium 145 mEq/L (reference range, 136-142 mEq/L), potassium 4.0 mEq/L (reference range, 3.5-5.0 mEq/L), calcium 9.0 mg/dL (reference range, 8.2-10.2 mg/dL), phosphorous 2 mg/dL (reference range, 4-

The clinical presentation and radiographs are consistent with chronic osteomyelitis. The MRI shows chronic changes of the distal femur with intraarticular (knee) extension. Chronic osteomyelitis is notable for a sequestrum, which is necrotic bone that has become avascular and no longer connected to the normal bone via the Haversian canal system. Involucrum refers to the new bone forming around the sequestrum. Often the involucrum will form a sinus tract allowing the sequestrum to drain into the soft tissues. Illustration A is a diagram of chronic osteomyelitis depicting the sequestrum (E), Involucrum (C), and sinus tract (D). In contrast to acute osteomyelitis, chronic osteomyelitis is often not eradicated with intravenous antibiotics alone. All necrotic bone (including the sequestrum) must be resected as it serves as a nidus for infection. Antibiotics should be guided off culture sampling of the infection.In the referenced article by Parsons and Strauss, the management of chronic osteomyelitis is reviewed.OrthoCash 2020

Numerous reports suggest an increased frequency of nutritional rickets in the US in children with dark skin pigmentation who are breast fed past 6 months of age without vitamin D supplementation. Nutritional rickets is rare in light-skinned children or those who are formula fed.

Closed chain kinetic exercises confer a margin of safety and are protective of healing or repaired tissues by the compressive nature of the applied forces. Closed chain kinetic exercise is associated with decreased shear, translation, and distraction of the joints within the chain. Because of patterns of motion with closed chain kinetic exercises, individual muscles may not be maximally strengthened or all joint motion returned to normal. Closed chain kinetic exercises may be used earlier in the rehabilitation process.