Biology, Genetics & Bone Healing MCQs

Ultraviolet light from the sun is needed for skin cells to transform 7-dehydrocholesterol into cholecalciferol (vitamin D3). Once in the cholecalciferol form, it will then go to the liver and get hydroxylated into 25-hydroxyvitamin D and then to the kidneys to become 1,25-dihydroxyvitamin D. Lack of sunlight does not influence the ability of the liver or kidneys to perform hydroxylation, but it does affect the ability of the skin to create cholecalciferol, which in turn means no 1,25-vitamin D. Lack of 1,25 vitamin D has a direct impact on the GI tract's ability to absorb calcium because the GI tract is an end organ affected by active vitamin D. The absence of 1,25 vitamin D would lead to increased levels of PTH, not decreased production of PTH.

Polymorphisms in the genes for the calcitonin receptor, estrogen receptor-1, vitamin D receptor, and the type I collagen alpha-1 chain (along with over 45 other genes) have been shown to be associated with osteoporosis. Answer 5, Cartilage oligomeric matrix protein, shows no current association with osteoporosis, but is the known genetic mutation associated with multiple epiphyseal dysplasia (a frequently tested fact). No single cause for osteoporosis has been shown at this point in time.Jin et al conducted a meta-analysis regarding polymorphisms in the 5' flank of COL1A1 gene and the conflicting results relating to osteoporosis. They found that the COL1A1 Sp1 polymorphism is associated with a modest reduction in BMD and an increased risk of fracture.The attached review by Huang and Kung discusses the multiple genetic and environmental determinants of osteoporosis and illustration A (from a different review by these same authors) lists the known genes currently associated with osteoporosis.The greatest biomechanical difference between unicortical and bicortical locking screws is seen when what force is applied?CompressionTorsionDistractionBending on the side of the plateBending on the surface perpendicular to the plateTorsion force has the largest biomechanical difference between unicortical locked screws and bicortical locked screws.The first referenced article by Roberts et al noted that by replacing the farthest unicorticalscrews (3 per side of the fracture) with bicortical locking screws, torsion resistance was increased by over 50%.The second referenced article by Fulkerson et al noted decreased resistance to all applied forces with unicortical screws in a comminuted fracture model, and recommended against their use in such a fracture.FOR ALL MCQS CLICK THE LINK ORTHOMCQ BANKYou are planning surgery on a 54-year-old female with the tibial plateau fracture seen in figures A and B. After reduction of the joint surface you plan to fill the void with a bone-graft substitute to prevent joint collapse. Which of the following bone-graft substitutesdisappears most quickly in vivo?Collagen-based matricesCalcium phosphateCalcium sulfateSynthetic calcium sulfate and tri-phosphate mixtureCoraline hydroxyapatiteCalcium sulfate disappears in vivo quickly, usually within 4-12 weeks. Calcium phosphate and coraline hydroxyapatite are resorbed slowly, somewhere between 1-10 years, depending on the manufacturer. Synthetics that combine calcium sulfate and phosphateresorb quicker than calcium phosphate but slower than calcium sulfate. Collagen-based matrices show quick resorption of the collegen but slow resorption of their hydroxyapatite coating. Walsh et al. examined the in vivo response of calcium sulfate pellets alone or in combination with autogenous bone graft in a sheep model. They found excellent bone formation in defects filled with calcium sulfate pellets. Immunostaining for various cytokines (BMP-2, BMP-7, PDGF, or TGF-beta)showed elevated levels in the newly formed bone. They proposed that the local environment acidity was responsible for breakdown of the calcium sulfate. Watson evaluated 8 patients with comminuted tibial metaphyseal fractures treated with an injectable calcium sulfate. They found that bone regrowth was observed in all patients and the bone substitute almost completely resorbed bymonths. Bucholz reviewed the biochemical, biomechanical, and longevity characteristics of the common bone substitutes.Which of the following Figures shows a fixation construct achieving absolute stability?Figure A shows percutaneous pinning, Figure B shows locked bridge plating, Figure C shows intramedullary nailing, Figure D shows lag fixation and neutralization plating, and Figure E shows external fixation. All except Figure D show relative stability constructs.Absolute stability is a construct seen in Figure D, where lag screws and a neutralization plate are shown in a postoperative clavicle. No micromotion is seen with this technique, and healing is by primary (Haversian) healing, as opposed to the other four constructs, which have relative stability and heal via callus formation. The first reference, the AO Principles textbook, covers this in depth.The second reference by Claes et al notes that bone can still heal with bone (as opposed to fibrous union) with strain rates up to 15%.Which immunoglobulin subtype does the rheumatoid factor target?IgAIgEIgMIgGRheumatoid factor does not target an immunoglobulinRheumatoid factor is an auto-antibody most commonly seen with rheumatoid arthritis. The presence of rheumatoid factor can also indicate generalized autoimmune activity unrelated to rheumatoid arthritis (e.g. tissue or organ rejection). Rheumatoid factor is itself an IgM antibody that is directed against the Fc portion of IgG antibody. Rheumatoid factor (IgM) attaches to IgG to form immune complexes which are deposited in tissues like the kidney and contribute to the overall disease process in rheumatoid arthritis.James et al. assessed the occurrence and predictive factors for orthopaedic surgery in an cohort of patients with rheumatoid arthritis. Risk factors for surgery varied but the authors found that decreased inflammatory markers during the first year after diagnosis decreased the risk for subsequent surgery.The positive predictive value is defined as which of the following?True positives / (true positives + true negatives)False negatives / (false negatives + true positives)False positives / (false positives + false negatives)(True positives + false positives) / (true negatives + false negatives)True positives / (true positives + false positives)Corrent answer: 5The positive predictive value is defined as the true positives divided by the sum of the positive results (true positive and false positive). It is also defined as the probability that a patient with a positive test actually has the disease; it is dependent on prevalence of disease.The referenced articles by Wojtys and Kuhn et al are two of a series of medical statistics review papers.An 85-year-old woman undergoes the treatment seen in Figure A for a displaced left femoral neck fracture. During wound closure, the patient becomes hypoxic and hypotensive. Despite aggressive resuscitation efforts, she passes away three hours later in the intensive care unit. The autopsy findings seen inFigure B from the patient's lungs are most likely the result of which of the followingReaming for the femoral componentInsertion of a femoral component after cement pressurizationUtilization of undersized broaches during canal preparationInadequate beta blockadeUse of spinal anesthesiaThe clinical scenario is consistent with fat emboli syndrome. Figure A, shows a cemented bipolar hemiarthroplasty while Figure B shows marrow embolization into the lungs.Studies have shown that intramedullary pressure and fat embolization are greatest during pressurization of cement and implant insertion.Intramedullary pressure is influenced by size, shape, sharpness and insertion rate of an implant. Pressurization during cementing of a femoral component generates a large degree of pressure over a much wider surface area than in the other methods described of femoral canal instrumentation or preparation, as the entire femoral canal ispressurized at one time. This results in the highest degree of marrow embolization to the lungs resulting in hypoxia.Dobrjanski et al studied which variables affected intramedullary pressurization and found that lower implant insertion speed, lower hammering force, arubber- compared with steel-tipped hammer and a larger synthetic bone-to- implant radial gap reduced intramedullary pressure generated in a femur module.Sustained compression applied to a growth plate under experimental conditions has what effect?No effectAccelerated longitudinal growthDecelerated longitudinal growthDecelerated apposition growthDecreased bending strength of the boneThe Heuter-Volkmann Law states that compression across the growth plate slows longitudinal growth.Stokes et al demonstrated that sustained compression across the growth plate can decrease longitudinal growth by 40%. Tension across the physis increases growth, but to a lesser degree.A 13-year-old girl with a displaced proximal tibia fracture is brought into the emergency department by her adult cousin. Thefracture needs surgical management. The child is living with her cousin's family while her parents are in Germany. While the child speaks fluent English, her cousin and her parents are German-only speaking. How should you consent this patient?No consent is needed given the urgent nature of the injury, proceed with surgeryTalk with the cousin, using the child as a translatorTalk with the cousin, using a German-translatorCall the parents in Germany, using the child as a translator over the phoneCall the parents in Germany, using a German-translator over the phoneThis is an urgent (not emergent) clinical senario, and as such, the child needs to haveformal consent by speaking with her parents using a German- translator.Wenger and Lieberman discuss the problems and potential solutions surrounding the process of informed consent in patients who either personally lack capacity to make decisions or in patients who require surrogates (like minors) to make treatment decisions.Lindseth reviews the ethical issues encountered in pediatric orthopaedics and the problems associated with these decisions. Specifically pediatric consent is confounded because the person giving the consent is not the person who will bear the consequences of the treatment.What is the primary mode of bisphosphonate excretion?RenalGastrointestinalLiverSkinPulmonaryBisphosphonates are a broad class of medicines used to treat osteoporosis and Paget's disease. They work by inhibiting osteoclast-mediated resorption after being absorbed into the inorganic phase of bone and taken up by osteoclasts. The paper by Lin et al provides a nice review of bisphosphonates and describe their appropriate use in enhancing bone density in patients with structurallyflawed bone. They describe the mechanism of action of bisphosphonates as pyrophosphate analogues and their renal mechanism of excretion, thus, prohibiting their use in patients with renal insufficiency. Rosier discusses the role of the orthopaedic surgeon in the diagnosis and treatment of patients with osteoporosis, now referred to as the "own the bone" initiative. Central to the treatment of osteoporosis are bisphosphonates and the anti-RANKLmonoclonal antibody, Denosumab.The 2009 AAOS Clinical Guideline on prevention of pulmonary embolism in patients undergoing total hip or knee arthroplasty recommends classifying patients as having either a "standard" or "elevated" risk of bleeding complications. The presence of all of the following qualify a patient as having an "elevated" risk of major bleeding EXCEPT?History of hemophiliaHistory of protein C deficiencyHistory of a recent gastrointestinal bleedHistory of a recent hemorrhagic strokeHistory of Von Willebrand's DiseaseThe 2009 AAOS Clinical Guideline on prevention of pulmonary embolism in patients undergoing total hip or knee arthroplasty recommends that all patients pre-operatively should be classified as either having an elevated or standard risk of bleeding and either an elevated or standard risk of pulmonary embolism.A history of a bleeding disorder (e.g., hemophilia, Von Willebrand's Disease), recent GI bleed, or hemorrhagic stroke qualifies a patient as having an elevated risk of major bleeding.A history of hypercoagulable state (such as protein C deficiency) or previous documented pulmonary embolism qualifies a patient as having an elevated risk of pulmonary embolism. Type of thromboembolism prophylaxis is recommended by weighing risk of major bleeding vs risk of PE. For those patients with a known contraindication to anticoagulation an IVC filter is considered. Mechanical prophylaxis is recommended across all risk (low tohigh risk of either bleeding or pulmonary embolism) groups undergoing total hip or total knee arthroplasty. The detailed AAOS guidelines can be found on the AAOS website.The evidence based clinical recommendations are presented in the reference by Johanson et al.In consideration of a prosthetic knee, each of the following are advantages of choosing a polycentric knee with fluid control over a constant friction knee EXCEPT:Allows variations in cadenceFlexes in a more controlled mannerLighter in weightImproved stance control allows less energy expenditureOverall length of the limb is shortened during initiation of a step reducing the risk of stumblingSingle axis, constant friction knees function as a simple hinge. They are light, durable, and much cheaper prostheses making them ideal for growing children who will need multiple prostheses before reaching adulthood. This prosthesis allows only a single speed of walking, and relies solely on alignment for stance phase stability. Polycentric knees offer each of the advantages stated above making it a more ideal prosthesis for the active adult. Disadvantages of the polycentric knee include cost, weight, and more sophisticated maintenance.Tang et al reviews the current prosthetic options for leg and foot amputees. Illustration A demonstrates a single axis knee prosthesis.Illustration B demonstrates a polycentric knee prosthesis.Which of the following biologic agents commonly used to treat rheumatoid arthritis (RA) DOES NOT target tumor necrosis factor- alpha (TNF-alpha)?InfliximabRituximabEtanerceptGolimumabAdalimumabRituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. Rituximab is used in combination with methotrexate to treat RA that has not responded to one or more types of treatment, including anti-tumor necrosis factor (TNF) blockers.In rheumatoid arthritis, and other chronic inflammatory conditions, cytokines produced by activated T-cells/macrophages contribute to the pro-inflammatory state. TNF-alpha is thought to be one of the major cytokines involved in rheumatoid arthritis pathology. As a result, many biologic agents used to treat RA are directed towards blocking TNF-alpha or its receptors. These drugs are able to reduce inflammation and stop disease progression.Elliot et al. evaluated the safety and efficacy of infliximab in 20 patients with active RA in an open phase I/II trial lasting 8 weeks. They found that treatment with anti-TNFa was safe, well tolerated and resulted in significant clinical and laboratory improvements.Illustration A depicts five commonly used anti-TNF alpha biologic agents for the treatment of rheumatoid arhtirits with their usual dosing regimens.Incorrect Answers:Receptor activator of nuclear-factor kappa-B ligand (RANKL) isan important regulator of bone resorption. Which of the following cells is the MAJOR source of RANKL in bone remodelling?OsteoclastsOsteoblastsIntegrinsT cellsMacrophagesRANKL, a key osteoclastogenic protein, is expressed by osteoblasts and binds to the RANK receptor on osteoclast precursor cells.The binding of RANKL to RANK on osteoclast precursor cells drives their differentiation into mature osteoclasts (multinucleated giant cells). Mature osteoclasts bind to the bone surfaces via integrins and resorb bone via their ruffled border within Howship's lacunae. Osteocytes orchestrate bone resorption and bone deposition by controlling osteoclast and osteoblast activity. Osteoblasts release RANKL to induce osteoclast differentiation, whileosteoblasts release osteoprotegerin (OPG) to downregulate osteoclastogenesis. Osteocytes also release fibroblast growth factor-23 (FGF-23), BMPs and sclerostin to regulate osteoblast activity. Antibodies to RANKL and Sclerostin have both been shown to increase bone density.Compton et al. reviewed osteocyte function and the emerging importance of sclerostin, which is a glycoprotein. Sclerostin is predominantly secreted by osteocytes under physiologic conditions to act as an important negative regulator of bone mass through inhibition of bone formation by osteoblasts.Illustration A demonstrates local bone milieu. It depicts the interplay between osteocytes, osteoblasts, and osteoclasts via the factors described above.Incorrect answers:A 45-year-old woman with rheumatoid arthritis is being scheduled for a total knee athroplasty in 2 weeks. She is currently taking sulfasalazine, Penicillamine, and etanercept, a tumor necrosis factor inhibitor (aTNF-a). What changes should be made to her medication regimen prior to surgery?Discontinuation of all three medications 1 weeks prior to surgeryDiscontinuation of sulfasalazine 1 weeks prior to surgery, continuation of etanercept and penicillamineContinuation of sulfasalazine, penicillamine, and etanerceptContinuation of sulfasalazine and penicillamine, discontinuation of etanercept 1 week prior to surgeryContinuation of penicillamine, discontinuation of sulfasalazine and etanercept 1 week prior to surgeryAnticytokine disease-modifying antirheumatic drugs (DMARD) have become increasingly popular in the treatment of RA. Immunosuppression and the risk of infection are potential complications for all anti-TNF-alpha medications. Current recommendations for cessation of immunosuppressive therapy are when the drug concentrations are at their lowest levels which include the following: 3 days after etanercept injection; 2 weeks prior to infliximab infusion; 10 days after adalimumab injection. Medications such as sulfasalazine and penicillamine may be continued during the pre and post- operative period. Recent evidence and guidelines such as those reviewed by Keith's paper, suggest that anti-TNF-alpha medications should be stopped 4 weeks prior to surgery.Giles et al report in their case control series an increased infection rate of RA patients undergoing an orthopaedic procedure who were on TNF-a inhibitors as opposed to patients on more traditional treatment regimens like methotrexate and prednisone.Which of the following supplements affects blood clotting through its effect on platelets?GinkgoVitamin DEphedraSt. John's WortSeleniumGinkgo and ginseng are two common supplements used in the general population that have inhibitory effects of platelet function. Adverse peri- operative complications consisting of increased bleeding and hematoma formation have been reported with the use of these two herbal supplements. The most commonly used supplements that could have an effect in the peri- operative period include echinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and valerian. Bleeding has been shown to be effected by garlic, ginkgo, and ginseng; cardiovascular instability from ephedra; and hypoglycemia from ginseng. Kava and valerian have pharmacodynamic herb- drug interactions that can increase the sedative effect of anesthetics. St John's wort has been shown to alter the metabolism of certain drugs used in the perioperative period.Ang-Lee et al review common supplements used today and their potential anesthesia/operative effects. The article places emphasis on proper history taking of not only medications but also supplements which is often times left out of documentation.The femur radiograph of a healthy 25-year-old female is compared to the femur radiograph of a healthy 85-year-old female. Which of the following best describes the 25-year-old's femur?Increased cortical thickness and a smaller medullary canal volumeDecreased cortical thickness and a larger medullary canal volumeEquivalent cortical thickness and medullary canal volumeIncreased cortical thickness and larger medullary canal volumeDecreased cortical thickness and a smaller medullary canal volumeAs the human body ages the cortical thickness/area decreases and subsequently the diameter/volume of the medullary canal increases. Therefore, a young healthy 25- year-old woman should have thicker cortices and a smaller medullary canal volume than her counterpart at 85 years. A decreased cortical bone area is linked to increased fracture risk.Stein et al studied femurs from subjects aged 21-92 years of age. They found that a reduction in cortical area was seen in older specimens and this change was morepronounced in female specimens.Wrong Answers:Which of the following is NOT a described complication of corticosteroid injections?Local flare in surrounding tissuesApoptosis of myocytesSkin pigmentation changesFat atrophyFacial flushingCorticosteroids have not been shown to cause apoptosis of myocytes when injected extra-articularly. Each of the other answers have been described.Cole and Schumacher provide a review of current uses of corticosteroid injections, and emphasize that how accurately the injection is placed affects the outcome.Kumar and Newman report prospectively on 672 patients who received 1147 intra- and extra-articular injections. Their overall complication rate was low (16%) with injection site pain (mild) and bleeding constituting the majority of cases. There were 4 instances of fat atrophy in the extra-articular group, andcases of syncope or dizziness in the intra-articular group. They did not discuss the efficacy of their injections.A surgeon chooses a periarticular locking plate with unicortical proximal locking screws for an extra-articular distal femur fracture as seen in Figure A. Compared to an identical construct with bicortical unlocked proximal screw fixation, the periarticular locking plate with unicortical locking screws has which biomechanical properties?Greater torsional and axial fixation strengthLess torsional but greater axial fixation strengthEqual torsional and axial fixation strengthGreater torsional but less axial fixation strengthLess torsional and axial fixation strengthUnicortical locking plates have characteristically less torsional strength than bicortical locking plates and bicortical non-locking plates. Axial strength is improved with locking plate fixation.Zlowodzki et al studied the LISS periarticular locking plate with unicortical proximal fixation in a distal femur model and found superior axial fixation strength (134%) but worse torsional strength (68%) compared to a fixed angle blade plate with non- locking bicortical screw fixation.Locked plating was reviewed by Haidukewych and Ricci which highlighted the added cost, unique complications, and they recommended the use of locked plating only in situations when unlocked constructs have demonstrated poor outcomes.In rat models looking at the effect of malnutrition on fracture healing, amino acid supplementation in a nutritionally deprived rat increases all of the following EXCEPTSerum albuminBody massQuadriceps total protein contentFracture callus mineralizationInsulin-like growth factor 1 (IGF-1) mRNA expressionThe study by Hughes et al found that essential amino acid supplementation (glutamine, arginine, and taurine) following femoral fracture in a protein- malnourished rat model increases serum albumin, body mass, quadriceps total protein content, and fracture callus mineralization. Expression of IGF-1 andIGF-2, myosin, actin, and VEGF mRNA were all significantly decreased in the amino acid supplemented group compared to the malnourished group. The malnourished group is thought to have upregulation of mRNA expression in attempt to increase the amount of protein product that is translated, however the lack of amino acid building blocks in the malnutrition group was a barrier to appropriate protein synthesis.The study by Day et al created a malnourished rat femur fracture model by administering a 6% protein diet. They found that administering a 20% protein diet in the post-fracture period yielded a greater cross-sectional area of thefracture callus and callus stiffness compared to the 6% protein malnourished group.The statistical power of a study is best defined by?1 - probability of type-II (beta) errorTrue positive/(true positive + false negative)True negative/(false positive + true negative)1 - probability of type-I (alpha) error[True positive/(true positive + false negative)] / false-positive rateThe power of a study is an estimate of the probability of finding a significant association in a research study when one truly exists. The power is defined by1 - probability of type-II (beta) error, and is often set at 80%. For example, a power of 80% means that if the intervention works, the study has an 80% chance of detecting this and a 20% chance of randomly missing it. A type-II or beta error occurs when one falsely concludes that there is no significant association when there actually is an association (resulting in a false-negative study that rejects a true alternative hypothesis). The type-II or beta error can be determined if Type I error rate and sample size are known. A type-I or alpha error occurs when a significant association is found when there is no true association (resulting in a false-positive study that rejects a true null hypothesis). The alpha level refers to the probability of a type-I (alpha) error and is usually set for most studies at 0.05. Answer 2 is the formula for sensitivity. Answer 3 is the formula for specificity. Answer 5 is the formula for the positive likelihood ratio. The references byKocher and Wojtys are excellent reviews of basic biostatistic principles.A 55-year-old female with a history of metastatic breast cancer develops shoulder pain without any trauma. Which of the following is involved with the findings shown in Figures A and B?IL-4RANKTNF-alphaOPGSox-9Osteoclastic bone resorption is the final common mechanism for osteolysis, whether due to a pathologic lytic lesion, macrophage activation in particle wear, or normal remodeling. The RANK-RANKL mechanism controls the coupling of osteoblast and osteoclast activation. Figures A and B show an osteolytic lesion in the humerus in a patient with known metastatic breast carcinoma.RANKL is expressed from osteoblasts and bone-marrow stromal cells. When RANKL binds to the RANK receptor (receptor/activator of NF-[kappa]B) on the cell membrane of osteoclasts it stimulates differentiation from osteoclast progenitor cells to mature osteoclasts. Mature osteoclasts proceed with osteoclastic bone resporption.Osteoprotegerin (OPG) acts as a decoy receptor by binding to RANKL and blocking the interaction between RANKL and the RANK-receptor and consequently inhibiting osteoclast formation andactivation.Illustration A depicts the RANK/RANKL involvement in tumor metastatic spread.Laboratory values of a normal serum calcium and parathyroid hormone can be found in which of the following disease states?Primary hyperparathyroidismType I vitamin D deficient ricketsType II vitamin D deficient ricketsX-linked hypophosphatemic ricketsNutritional ricketsHypophosphatemic rickets is caused by the inability of kidney proximal tubules to reabsorb phosphate due to a mutated PHEX gene, found on the X chromosome. PHEX is thought to protect extracellular matrix glycoproteins from proteolysis. Hypophosphatemic rickets shares many clinical similarities with nutritional rickets but shows PTH levels that are not elevated, even with calcium and phosphate abnormalities.Pettifor reviews the advances in molecular genetics in the understanding and possible treatments in tumour-induced osteomalacia/rickets.The review article by Carpenter discusses the X-linked disorder including its clinical manifestations, the wide spectrum of disease severity, and complications of the disease in adult patients.Illustration A is a table that details the laboratory values associated with each type of rickets.An 80 year-old female undergoes ORIF of her hip fracture without any complications. A hospitalist consult was obtained for medical clearance pre- operatively, and she was diagnosed with osteoporosis. Which of the following treatment scenarios will lead to the best management of the patient's osteoporosis?Schedule a follow-up appointment with the patients primary care physician to initiate therapyOrder a physical therapy consult and initiate an exercise planHave the patient meet with a nutritionist to increase her calcium and vitamin D intakeStart bisphosphonates, and have the patient follow-up with her primary care physicianPerform a metabolic work-up as an inpatient, and set-up an appointment in an osteoporosis clinicThe initiation of appropriate osteoporosis treatment following hip fractures occurs at a surprisingly low rate. Physical therapy and dietary changes are not appropriate initial treatments for osteoporosis, and bisphosphonate therapy should be prescribed by the physician who will be following and managing the patient's osteoporosis.Miki et al performed a prospective randomized trial where they compared the rates of osteoporosis treatment initiation. The percentage of patients who were on pharmacologic treatment at 6 months post-injury was 58% in the group whose treatment was directed by the orthopedic surgeon and osteoporosis clinic, and 29% when managed by the primary care physician alone.The elements chromium, molybdenum, and cobalt are basic components of which of the following implant materials?Aluminum oxideCobalt alloyStainless steelPMMATantalumCobalt alloys are extremely strong and are well-suited to applications requiring longevity. Strength of the implant is improved by the addition of molybdenum. Corrosion resistance is addressed by the addition of chromium, which also increases the hardness of the implant.Incorrect Answers:Which of the following scenarios of treatment of a humerus fracture best achieves low strain at the fracture site and high stiffness of the treatment construct?Functional bracing of a transverse midshaft fractureComminuted midshaft fracture with locked bridge platingShort oblique fracture with interfragmentary lag screw and locked neutralization plateUniplane external fixation of a spiral open fractureOblique fracture with intramedullary nail fixationStrain in fractures is calculated by dividing the interfragmentary movement by the size of the fracture gap. Strain must be very low (2%) for primary bone healing to occur, and should be less than 10% for secondary bone healing to occur. Stiffness refers the ability of the construct to resist movement under applied loads. Answer 3 describes a situation where primary bone healing isthe goal. For this to occur, there must be no significant gapping at the fracture site, there must be low strain between fracture fragments, and the construct must be stiff.None of the other answers would accomplish this. Functional bracing and intramedullary fixation both accomplish healing through formation of fracture callus, or secondary healing. A comminuted fracture treated with locked bridge plating relies on less stiffness to allow for secondary healing between fragments. However, since there are many fracture fragments, the strain is distributed among them and therefore remains low. A uniplane external fixator is very unlikely to accomplish low strain and high stiffness in this setting.A 67-year-old man complains of low-grade fevers and calf pain 2 weeks following a total knee arthroplasty. What is the next appropriate step in management of this patient?Plethysmography of lower extremityMRI of lower extremityCT angiography of lower extremityVenous ultrasonographyKnee aspiration to evaluate for septic jointVenous ultrasonography is the next best step in this patient's management, due to the clinical picture of a deep venous thrombosis. The most sensitive and specific recommended diagnostic procedure is a venous ultrasonography.In their multi-center study, Haut et al. hypothesized that admission to trauma centers that use duplex ultrasound more frequently would independently predict increased DVT reporting for individual patients. They indeed found that trauma centers ultrasound practice was an independent predictor of DVT diagnosis for individual patients, controlling for patient-level risk factors, but concluded the elevated DVT rates at these centers were due to surveillance bias. As such, they recommend that surveillance for DVT should not be considered as a quality control measure in the care of trauma patients.A patient undergoes closed reduction of a bimalleolar ankle fracture dislocation by the ER physician and is sent to your clinic for evaluation. You evaluate the patient and schedule him for surgery. According to the 2009 guidelines, which of the following scenarios would meet criteria for coding the encounter as a new patient?You injected his knee in the office almost 3 years ago for osteoarthritis, and have not seen him sinceHe had an arthroscopic operation by your partner 4 years agoYou were consulted 1 year ago for shoulder pain when he was hospitalized for chronic renal failureHe was seen by your partner in clinic for a herniated disk 2 years ago, but had no procedures performedYou performed a hip replacement on him 12 years ago, and his last follow- up was 18 months ago at which time he was doing wellOnly answer two is correct. The 2009 guidlines clarify that the patient can be defined as new only if he has not been seen by anyone in the physician's same group practice and of the same specialty in the past 3 years. Hand and sports medicine specialists with a CAQ, however, are an exception and are allowed to bill for patients already seen by other orthopedists in the same group as newpatients. This scenario would not qualify as a consultation, since the orthopedic surgeonis taking over care of the patient's problem and is not merely offering advice to another physician who is already caring for the patient. Consultations do not have the same 3 year time qualification. However, Medicare and many other insurers no longer recognize consultation codes.All the following medications binds reversibly to the enzyme COX-1 EXCEPTMeloxicamDiclofenacIndomethacinNaproxen sodiumAspirinAspirin binds irreversibly to the cyclooxygenase enzyme. Aspirin acetylates platelet cyclooxygenase and permanently inhibits thromboxane (TX) A2 production leading to its antiplatelet effects. The other NSAID's listed above bind reversibly with COX-1.Patrono et al discuss the pharmokinetics and platelet effect of both low dose and regular dose aspirin. Nonsteroidal anti-inflammatory drugs compete dose- dependently with arachidonate for binding to platelet cyclooxygenase.In the treatment of patients with rheumatoid arthritis, TNF-alpha is blocked by which of the following agents?TocilizumabAnakinraEtanerceptAbataceptRituximabEtanercept is a biochemically designed soluble p75 tumor necrosis factor receptor immunoglobulin G fusion protein, which blocks the downstreameffects of TNF.Methotrexate is a chemotherapy agent used to inhibit lymphocytes. Gold inhibits monocytes, while sulfasalazine is an anti-inflammatory decreasing the production ofprostaglandins and leukotrienes. Rituximab inhibits B-cells as itis a monoclonal antibody to CD20 antigen. Anakinra (Kineret) is a recombinant IL-1 receptor antagonist. Abatacept (Orencia) is a selective costimulation modulator that binds to CD-80 and CD-86 (inhibits T cells). Tocilizumab (Actemra)is an IL-6 receptor inhibitor (2nd line treatment for poor response to TNF-antagonist therapy).Pisetsky wrote an editorial in NEJM discussing the development of TNF blockers through research, and the potential for the use of Etanercept in patients with juvenile RA through its inhibition of lymphotoxin-alpha.Which of the following medications when combined with methotrexate has been shown to be more effective than methotrexate alone in the treatment of rheumatoid arthritis?NitrofurantoinRifampinAzithromycinErythromycinDoxycyclineTetracycline was initially used in the treatment of rheumatoid arthritis (RA) because Mycoplasma was thought to be the causative agent. It was later found that tetracyclines have biologic effects on the inflammatory and immunologic cascade by inhibiting collagenase activity. Collagenase is an enzyme involvedin breaking down macromolecules in the connective tissue, contributing to the pathologic changes of RA.In a prospective study, O'Dell et al found that initial therapy with methotrexate plus doxycycline was superior to treatment with methotrexate alone. Furthermore, similar results for low-dose and high-dose doxycycline suggested that antimetalloproteinase effects were more important than the antibacterial effects.When using C-arm fluorocopy, patient radiation exposure will be increased with which of the following?The extremity is positioned closer to the image intensifierA larger body part is imaged compared to a smaller body partUse of radiation beam collimationMini C-arm fluroscopy is used instead of large C-arm fluroscopyDecreased duration of imagingPatient radiation exposure will be increased if a larger body part is imaged compared to a smaller body part.The first study by Giordano et al used radiation dosimeters for large and mini c-arm machines. They found that elevated exposure levels can be expected when larger body parts are imaged, when the extremity is positioned closer to the x-ray source, and when the large c-arm is used over the mini c-arm.The second study by Giordano et al also used dosimeters for a mini c-arm and found that the surgical team is exposed to minimal radiation during routineuse of mini-c-arm fluoroscopy, except when they are in the direct path of the radiation beam. They list factors to decrease radiation exposure to patient and surgeon including: minimizing exposure time, reducing exposure factors, manipulating the x-ray beam with collimation, orienting the fluoroscopic beam in an inverted position relative to the patient, strategic positioning of the surgeon within the operative field, judicious use of protective shielding during imaging, and maximizing the distance of the surgeon from the radiation beam.Illustration A shows that arrangement #1 has the body part half-way between the radiation source and image intensifier. Arrangement #2 has the the image intensifier acting as an arm table for the body part with the radiation source further away. Arrangement #1 has more radiation exposure than #2. The distance between the x-ray tube and the body part is doubled in arrangement#2 compared to arrangement #1. This increased distance correlates to a reduction in exposure according to the inverse square law (reduction in radiation intensity with greater distance from the x-ray source).You are seeing a 13-year-old girl for asymptomatic flat feet and recommend observation. In educating this patient/family about general bone health, you recommend what amount of daily dietary calcium for your patient?

Bisphosphonates represent the most clinically important class of antiresorptive agents available to treat diseases characterized by osteoclast-mediated bone resorption. Two classes of bisphosphonates exist: nitrogen-containing and non-nitrogen-containing compounds. The non-nitrogen-containing bisphosphonates work by metabolizing into cytotoxic ATP analogs. The nitrogen-containing bisphosphonates work via the mevalonate pathway by inhibiting GTPase formation, leading to loss of GTP prenylation and eventual induction of osteoclast apoptosis.

Rickets is a condition of inadequate mineralization of osteoid and cartilage at the growing ends of bone in children. It is associated with a nutritional deficiency in children that affects open physes, as opposed to osteomalacia which is a deficiency in people with closed growth plates. There are classic radiographic findings and disorders that mimic rickets. Classic findings are widened physes related to widening of the physis from accumulation of nonmineralized osteoid and cartilage, irregular metaphyses, and loss of definition of the zone of provisional calcification. The changes are seen predominantly in the bones with greatest growth (tibia, distal femur, distal radius) and rarely seen in slower growing bones such as the tubular bones in the hand. Widening of the anterior ribs, the rachitic rosary, may be seen. Hyperparathyroidism with accumulation of fibrous tissue in the metaphyses can produce lucencies that may appear similar to the nonmineralized osteoid of rickets. Hyperparathyroidism has erosion around the edge of the growth plate. There are punched out lesions and resorption subperiosteally. Rounded epiphyses and marked separation of the epiphysis and metaphysis are the classic differentiation of Jansen syndrome, a dominantly inherited metaphyseal chondrodysplasia. Sclerotic metaphyseal ends are similar to rickets, but with maturation, the spaces fill with irregular calcification classic to Jansen syndrome. Sclerotic of the vertebra, or "rugger jersey" spine, is typical of renal osteodystrophy.

DISCUSSION: IGF-I, formerly known as somatomedin-C, possibly acts by both paracrine and endocrine hormone pathways. The products of the GH-IGF-I system induce proliferation without maturation of the growth plate and thus induce linear skeletal growth. The action of the thyroid hormone axis is via an active metabolite that enters target cells and signals a nuclear receptor to stimulate both proliferation and maturation of the growth plate. Increased amounts of the active steroid hormone metabolite promote proliferation and maturation of the growth plate. Calcitonin inhibits bone resorption. REFERENCES: Binder G, Grauer ML, Wehner AV, et al: Outcome in tall stature: Final height and psychological aspects in 220 patients with and without treatment. Eur J Pediatr 1997;156:905-910. Wang J, Zhou J, Cheng CM, et al: Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. Endocrinol 2004;180:247-255. Gertner JM: Childhood and adolescence, in Favus MJ (ed): Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, ed 4. Philadelphia, PA, Lippincott Williams & Wilkins, 1999, pp 45-47.

A DEXA scan is most appropriately used to establish a baseline score. Even if the bone mineral density is not within the osteoporotic range (T-score less than -2.5), a prior fragility fracture is a strong risk factor for a second fracture as a result of factors other than bone density, such as worsening vision or balance, confusion, or other predispositions to falls. The guidelines of the National Osteoporosis Foundation indicate that, following a fragility hip fracture, active anti-osteoporotic medication should be initiated, whether or not a DEXA scan is performed. A recent study showed that antiresorptive therapy following a hip fracture reduces not only the risk of a second fracture but also overall mortality.

The use of bisphosphonates has been recently associated with the development of osteonecrosis of the jaw. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor. Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density (ie, alendronate). The primary mechanism of action of these drugs is inhibition of osteoclastic activity, and it has been shown that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity, such as breast cancer and multiple myeloma, and have developed into a mainstay of treatment for individuals with these diseases. Although shown to reduce skeletal events, there has been no improvement in patient survival.

Calcitonin is a hormone that reduces serum calcium concentration by directly interfering with osteoclast maturation via receptors. Calcitonin inhibits phosphate reabsorption and decreases calcium reabsorption in the kidneys. By attenuating cartilage breakdown and stimulating cartilage formation via inhibitory pathways of matrix metalloproteinases, calcitonin also has a chondro-protective effect on articular cartilage. Calcitonin has no major effects on intestinal absorption of calcium, but may aid in small-bowel secretion of sodium, potassium, chloride, and water. Calcitonin also has no receptor effect on osteoblasts.

Because the radiographs reveal poor regenerate bone, especially anteriorly and laterally, the first step in management is to slow the distraction rate. If this does not solve the problem, temporary reversal of the distraction, or “accordionization,” can be used to induce a greater healing response. Maintaining the same distraction rate will further impair regenerate formation and delay healing. Bone grafting should be reserved as an option if decreasing the distraction rate or alternating a week of compression with a week of distraction fails to improve the callus formation. Repeat corticotomy is performed in patients with premature consolidation.

BMP proteins, which are part of the larger transforming growth factor-beta superfamily, bind to serine/threonine receptors on the cell surface. This binding causes phosphorylation of SMAD proteins, which in turn forms a complex that enters the nucleus and initiates the transcription of several genes involved in osteoblastic differentiation. Adenylate cyclase is a transmembrane protein that acts intracellularly to activate the G protein pathways. Myc is a proto-oncogene that encodes for a transcription factor involved in numerous cell-activation pathways, but is not directly phosphorylated by BMP receptor. β-catenin is an intracellular molecule that plays a key role in the Wnt signaling pathway.

According to the World Health Organization, a patient with a BMD T-score of -2.5 or lower is considered to have osteoporosis. A score between -1.0 and 2.5 is considered osteopenia. The BMD T-score provides no information about metastatic bone disease.

This patient has familial hypophosphatemic rickets, a vitamin D-resistant form of rickets that is an X-linked inherited disorder. Patients are short (< 10th percentile). Varus occurs both in the distal femur and proximal tibia. Patients have increased urinary excretion of phosphorus, leading to hypophosphatemia. Calcium levels are within defined limits and vitamin D levels can be normal as well. Treatment should include phosphate and 1,25 dihydroxy vitamin D3 (calcitriol). Phosphate administration increases the plasma concentration,which lowers plasma ionized calcium concentration and further reduces plasma calcitriol concentration (removal of hypophosphatemic stimulus). Secondary hyperparathyroidism results because of both hypocalcemia and removal of thenormal inhibitory effect of calcitriol on parathyroid hormone (PTH) synthesis. Elevated PTH levels will increase urinary phosphate excretion, defeating the aim of oral therapy.Addition of calcitriol is necessary to increase the intestinal absorption of calcium and phosphate to prevent secondary hyperparathyroidism. Massive doses of vitamin D alone can restore normal radiographic appearances to the epiphyses, but normal growth is not restored unless phosphate replacement is adequate.A 35-year-old woman began to train for a half marathon. After 8 weeks of increasing her mileage, what changes can you expect in her Achilles tendon?Net decrease of type I collagenNet increase of type I collagenIncreased diameter of collagen fibrilsIncreased cross-sectional area of the tendonTraining increases turnover of type I collagen, promoting both synthesis and degradation of collagen and a net increase synthesis of type I collagen in tendon-related tissue.Strenuous endurance training has resulted in decreased collagen cross-links, suggesting increased collagen turnover, but decreased collagen maturation. In human studies, physical training results in increased turnover of collagen. Synthesis and degradation are elevated initially when beginning an exercise program, but degradation products decrease overall. It is not known if activity levels in humans affect the diameter of collagen fibrils or the cross-sectional area of tendons.FOR ALL MCQS CLICK THE LINK ORTHOMCQ BANK

DISCUSSION: Hypophosphatemic rickets is an inherited disorder that is transmitted by a unique sex-linked dominant gene. Therefore, if a male patient has a female offspring, his affected X chromosome will be transmitted and all of his female children will have hypophosphatemic rickets. All male offspring of a male patient will be unaffected. All offspring of a female patient have a 50% chance of having the disorder. Understanding the inheritance of hypophosphatemic rickets facilitates early diagnosis and early treatment. Medical treatment with phosphorus and some types of vitamin D (most authors recommend calcitriol) improves, but does not fully correct, the mineralization defect in hypophosphatemic rickets. However, if medical treatment is begun before the child begins walking, the growth plate is then adequately protected and a bowleg deformity will most likely be prevented.

Tendons consist of mainly type I collagen (95%); a small amount of collagen types III, V, VI; and proteoglycans (< 5%). Proteoglycans have highly charged glycosaminoglycan side chains that attract water and help keep tendons well hydrated. Decorin is the most common proteoglycan in tendons and has been shown to bind to collagen. Tenascin-C is a glycoprotein upregulated in tendinopathy.

TGF-beta 1 stimulates the synthesis of extracellular matrix (ECM) and causes synovial proliferation and fibrosis.TGF-beta is the most thoroughly investigated member of the TGF-beta superfamily. This group includes TGF-beta1, BMP-2, and BMP-7. Besides the above activities, TGF-beta1 also stimulates chondrocyte synthetic activity and decreases the catabolic activity of IL-1.Fortier et al. reviewed the role of growth factors in cartilage repair and modificationof osteoarthritis. They found that members of the TGF-beta superfamily, FGF family, IGF1, and PDGF have all been investigated as possible treatment augments in the management of chondral injuries and early arthritis. They concluded that more research was necessary before routine application.Illustration A shows a summary of the different growth factors and their effects on cartilage.Incorrect Answers:

Osteoclasts resorb bone. Osteoclasts are derived from monocytes and macrophages that fuse to form multinucleated cells in response to receptor activator of nuclear factor kappa B (RANKL) and macrophage colony stimulating factor (MCSF). Osteoclasts attach to bone surfaces through a specific cell attachment receptor called an integrin (avβ3 or vitronectin receptor). The ruffled border refers to multiple invaginations of plasma membrane against the bone matrix surface. Lysosomes move to the ruffled border of osteoclasts and discharge lysosomal enzymes into the resorption region. These enzymes include cathepsin K, matrix metalloproteinase, and carbonic anhydrase (CA II).

Allograft bone is one of the most common bone graft substitutes, and is frequently used as a bone graft extender. The sterilization process kills all cells but their three-dimensional structure is retained, offering an osteoconductive scaffold. Tricalcium phosphate, calcium phosphate, and calcium sulfate are also osteoconductive materials with a three-dimensional scaffold similar to native cancellous bone. Bone morphogenetic protein is an inductive protein, which stimulates osteoprogenitor cells to differentiate along a bone-forming lineage.

Dkk-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 β-catenin. The unphosphorylated β-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, β-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/β-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.

Alendronate 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 insufficiencyfractures 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 with uterine cancer or a detached retina.

The kidneys are responsible for monitoring and regulating calcium homeostasis as well as for controlling levels of phosphate, magnesium, and other minerals. Thekidneys act both as target organs for parathyroid hormone (PTH) and for excreting it. The proximal convoluted tubules of the kidneys are the site of production of 1,25-dihydroxycholecalciferol (the active form of vitamin D following hydroxylation of 25-hydroxycholecalciferol catalyzed by 1-hydroxylase), the foremost regulator of intestinal calcium absorption. This hormone also promotes osteoclastic resorption of bone and the feedback inhibition of PTH synthesis. Modest changes in the efficacy of renal excretion dramatically alter the body's ability to maintain mineral homeostasis. Phosphate reduces urine calcium excretion through several extrarenal mechanisms. An increase in phosphate will directly stimulate PTH secretion and can reduce ionized calcium, also enhancing PTH secretion. The increased PTH will enhance calcium resorption. Phosphate will complex with calcium in the intestine, decreasing the amount of calcium for absorption. It can also complex with calcium in the bone and soft tissues, decreasing the filtered load of calcium. Decreased phosphate will result in hypercalcuria. There appears to be a direct effect of phosphate to decreased calcium reabsorption in the distal nephron.