Biology, Genetics & Bone Healing MCQs

Several cancers directly produce receptor activator of nuclear factor kappa beta ligand (RANKL) which leads to bone resorption and the lytic lesions seen on radiographs.Cancers that originate or metastasize to bone can be blastic, lytic, or mixed when viewed on radiographs. Lytic lesions appear radiolucent due to bone resorption that occurs around the cancer cells. This is secondary to direct production and release of RANKL by the cancer cells themselves. RANKL then stimulates osteoclastogenesis and an increase in local bone resorption. Denosumab is a monoclonal antibody against RANKL that has been shown to decrease rates of pathologic fractures.Lynch et al. review the progression of metastatic disease. They note that cancer cells can stimulate both osteogenesis and osteolysis, and that this pathologic increase in bone matrix turnover is what allows the cancer to progressively expand or metastasize to distant sites. They discuss the role of matrix metalloproteinases as primary regulators of this process.Illustration A is a diagram illustrating how the binding of RANKL to receptors on the surface of osteoclast precursors activates them and begins the process of bone resorption. Cancer cells can directly produce RANKL thus increasing the rate of local bone resorption.Incorrect Answers:

Chronic Vitamin D deficiency leads to problems with bone health and has been shown to increase the risk of falls in the elderly. Appropriate supplementation of Vitamin D has been shown to decrease this risk. Conversion in the skin decreases with age and may be nearly nonexistent in darkly pigmented individuals. Vitamin D3 is the preferred form for supplementation, but D2 is the form most available by prescription in the US. Hypervitaminosis D is rare and very high doses can be tolerated without significant concern for toxicity. Because the patient has sustained one insufficiency fracture, she is at risk for insufficiency fractures in other skeletal locations, rendering expectant observation insufficient. Her serum calcium is normal, and with a low Vitamin D level, calcium utilization in her system would be inadequate. Bisphosphonate therapy in addition to calcium and vitamin D supplementation may provide a good long-term solution, but should not be instituted until the bone mineral imbalance has been adequately corrected. Surgical fixation of this fracture is not indicated, particularly in lieu of improving symptoms.

The only factor that is prognostic for outcomes is the quality of the reduction. None of the other factors has any effect on the outcome. Early range of motion or physical therapy may offer temporary effects, but these small advantages do not last beyond 3 months after surgery.

Gout is an inflammatory arthritis caused by the presence of monosodium urate crystals in the joint. It is characterized acutely by a painful joint that remits after 1 to 2 weeks and recurs periodically. The diagnosis of gout can be made by confirming the presence of monosodium urate crystals in the joint fluidaspirated from the inflamed joint. Patients with gout may also have tophaceous deposits within the skin or bursae of the extremities. Elevated urine pH, serum uric acid, and serum phosphate can all be associated with numerous conditions and are not specific to gout. Calcium pyrophosphate crystals are associated with chondrocalcinosis (pseudogout).A 72-year-old woman is evaluated for sacrococcygeal pain sustained after a twisting injury. Radiographic and MRI evaluation confirms the presence of a nondisplaced fracture at the sacrococcygeal junction. Over a 3-week period, the pain has gotten significantly better. No additional lesions or injuries are noted.Laboratory studies show a serum calcium level of 8.8 mg/dL (normal 8.6-10.3 mg/dL) and a 25-OH Vitamin D level of 14 ng/mL (normal80 ng/mL). What is the most appropriate treatment for this patient?Expectant observationCalcium supplementationHigh dose vitamin D supplementationBisphosphonate therapySurgical fixation of the sacrococcygeal fractureChronic Vitamin D deficiency leads to problems with bone health and has been shown to increase the risk of falls in the elderly. Appropriate supplementation of Vitamin D has been shown to decrease this risk. Conversion in the skin decreases with age and may be nearly nonexistent in darkly pigmented individuals. Vitamin D3 is the preferred form for supplementation, but D2 is the form most available by prescription in the US. Hypervitaminosis D is rare and very high doses can be tolerated without significant concern for toxicity. Because the patient has sustained one insufficiency fracture, she is at risk for insufficiency fractures in other skeletal locations, rendering expectant observation insufficient. Her serum calcium is normal, and with a low VitaminD level, calcium utilization in her system would be inadequate. Bisphosphonate therapy in addition to calcium and vitamin D supplementation may provide a good long-term solution, but should not be instituted until the bone mineral imbalance has been adequately corrected. Surgical fixation of this fracture is not indicated, particularly in lieu of improving symptoms.Figures 70a and 70b show the radiograph and MRI scan of a 66- year-old man who has fatigue, weight loss, and muscle weakness. Examination reveals marked pain and discomfort in the left mid leg. Biopsy specimens are shown in Figures 70c and 70d. What is the most likely diagnosis?MastocytosisMultiple myelomaHyperparathyroidismMetastatic carcinomaMulticentric giant cell tumorThe signs and symptoms of hyperparathyroidism are similar to those in patients with diffuse skeletal metastases. Serum markers are very helpful in making the diagnosis. In this patient, the radiograph shows multiple lesions in the tibia and proximal fibula that have a variable appearance. For example the mid-tibial lesion is radiolucent and slightly expansile whereas the more proximal tibial lesions are radiodense. The proximal fibula lesion is mixed (radiolucent/radiodense). These findings would be very uncommon in patients with myeloma, metastatic disease, or multicentric giant cell tumor. The histopathology shows a bland fibrous stroma with multiple multinucleatedgiant cells. On higher power, the stromal cells are spindled and the giant cells are relatively small in contrast to giant cell tumor where the giant cells are larger and the stromal cells are more rounded with nuclei that closely resemble those in the giant cells.There is blood extravasation (stromalhemorrhage) and hemosiderin deposition. The constellation of findings is most consistent with brown tumors due to hyperparathyroidism (secondary to a parathyroid adenoma in this patient).A 68-year-old woman has had progressive pain in the right thigh for the past several months. She has a history of hypertension, treated with hydrochlorothiazide and osteoporosis treated with alendronatefor 10 years. At this point, she is virtually wheelchair bound.Radiographs are shown in Figures 78a and 78b. Additional studies show no signs of systemic disease. What is the most likely etiology of her condition?Prolonged use of bisphosphonatesUse of calcium-wasting diureticsOccult metastatic cancerVitamin D-resistant ricketsDisuse osteopeniaThe patient has been on alendronate for 10 years and has evidence of a proximal diaphyseal fatigue fracture. These have been associated with long- term use of bisphosphonates. Staging studies have failed to show systemic disease, and while metastasis with an unidentifiable primary does occur, it would be unlikely to present with this radiographic appearance, now recognized to be classic for stress fractures associated with chronic bisphosphonate usage. Hydrochlorothiazide does not cause calcium wasting. Vitamin D-resistant rickets would be a long-standing event and would present much earlier in life, often with pronounced deformities. Whereas the patient's progression to intolerance of weight bearing likely has led to some degree of disuse osteopenia, the underlying problem is the long-term bisphosphonate exposure.A surgeon recommends an interscalene regional block to a patient undergoing shoulder arthroscopy. When asked about potential complications, which of the following is most likely to occur?Persistent motor neuropathySensory neuropathyComplex regional pain syndromePneumothoraxCardiac arrythmia and arrestSensory neuropathy is the most common complication seen with interscalene regional block.FOR ALL MCQS CLICK THE LINK ORTHOMCQ BANKBishop et al. retrospectively reviewed 478 patients who had shoulder surgery under interscalene regional block. A total of 462 patients (97%) had a successful block. While all of the answers have been described, in this study no patient had a seizure, pneumothorax, cardiac event, or other major complication. Twelve (2.3%) of the 512 patients who had a block had minor complications, which included sensory neuropathy in eleven patients and a complex regional pain syndrome that resolved at three months in one patient. For ten of the eleven patients, the neuropathy had resolved by six months.Cathepsin K is an enzyme produced by osteoclasts. What is the function of cathepsin K?Reduction of disulfide bonds in the extracellular matrixBone resorptionActivation of RANK (Receptor activator of nuclear factor kappa-B)Antagonize the action of RANKAbsorb water in the extracellular matrixCathepsin K is an enzyme produced and released by osteoclasts at the ruffled border that functions to resorb bone. Cathepsin K inhibitors are being clinically evaluated as potential anti-resorptive drugs for use in osteoporosis treatment. Other proteins associated with osteoclasts include tartrate-resistant acid phosphatase (TRAP) and calcitonin receptor.Illustration A is a drawing that depicts the action of cathepsin k within osteoclasts.What is the primary problem in rickets osteomalacia?Defect in the zone of proliferation within the physisDefect in type I collagenDefect in the ext-1 geneLow level of calciumProduction of dysplastic fibrous boneRickets is a disorder of bones in children that results from decreased calcium available in the blood resulting in poor mineralization of bone that can lead to fractures and deformity. The most common cause of rickets is from vitamin D deficiency but it can also be caused by poor nutrition or gastrointestinaldisease that results in poor calcium absorption such as celiac disease or severe diarrhea from other causes. Rickets is not primarily a physeal disorder. Osteogenesis imperfecta is caused by a defect in type I collagen. A defect inthe ext-1 gene is often seen in patients with multiple hereditary exostoses. Fibrous dysplasia also can result in bone deformity and fractures due to production of dysplastic fibrous bone but is not caused by calcium or vitamin D deficiency.If an orthopaedic surgeon receives royalties from a company for his or her participation in the design and development of a product, and uses that same product for the care of his or her patients, what is the orthopaedic surgeon's obligation?Obligated to disclose only the fact that he or she was involved in the design and developmentObligated to disclose only the company relationship if there is a state law requiring itObligated to disclose his or her full relationship with the company, including the fact that he or she receives royaltiesNo obligation to disclose this private matter to the patientAvoid this situation because it should not exist since he or she cannot use such a productThe AAOS has a specific code of ethics and professionalism that addresses this issue: "When an orthopaedic surgeon receives anything of value, including royalties, from a manufacturer, the orthopaedic surgeon must disclose this fact to the patient." It is derived from a broader document developed by the American Medical Association, and is applicable to all physicians. At present, this is an ethical issue receiving greater federal scrutiny. This issue has had a greater effect on the public's perception of the integrity of the orthopaedic profession.A minimally invasive plate osteosynthesis is seen in Figure 15. The resultant fracture healing can best be attributed to a fixation construct that wasstiff and stable.flexible and stable.facilitating direct osteonal healing.inhibitory to endochondral ossification.stimulatory to intramembranous ossification.Locked plating constructs with long-working lengths provide flexible but stable constructs that promote (not inhibit) endochondral ossification. Because of the longer working length they are not stiff, and these fractures do not heal with intramembranous ossification which occurs in bones like the calvarium. Direct osteonal healing is usually seen with constructswhere absolute stability is achieved through interfragmentary compression, unlike in this case.An orthopaedic surgeon makes an incision on a right knee and realizes that the patient was supposed to have a left total knee arthroplasty. The surgeon should do which of the following?Leave the wound open and talk to the family immediately.Close the wound, abort the surgery, and talk to the patient and family when the patient is awake.Close the wound, complete the left knee arthroplasty, and talk to the family after the surgery is complete.Complete the surgery and talk directly to the patient the following day on rounds.Discuss the problem in the office the next week in a calm reassuring manner.The AAOS recommendation is to complete the correct surgery, repair the incorrect surgery to as close to normal as possible, and then discuss it openly with the family after the surgery is complete. Prompt informing is necessary. Aborting the surgery then results in the patient requiring a second anesthesia and surgical time needlessly.Spindled cells that are surrounded in mature osteoid thatconnect to other similar cells via canaliculi are best described as which of the following?OsteoblastsOsteoclastsOsteocytesHistiocytesMegakaryocytesOsteocyte cell processes travel through canaliculi to interconnect with other osteocytes and cells on the bone surfaces. Osteoblasts are cells that produce bone matrix and are seen rimming immature bone. Osteoclasts are large multinucleated cells that resorb bone and are found in Howship's lacunae. Megakaryocytes and histiocytes are found in marrow but not mature bone cortex.A 48-year-old woman has an open subtrochanteric femur fracture. No other injuries are reported. After thorough evaluation, it is determined that she will need emergent surgical fixation. The patient and family indicate that they are practicing Jehovah's witnesses and desire adherence to the religious standards with respect to blood product usage. The patient signs a valid advanced directive confirming these wishes. Which of the following would be considered acceptable treatment?Whole bloodPlateletsPlasmaStarch product (ie, Hetastarch, Hespan)Donor-directed blood from a family member who is a practicing Jehovah's witnessJehovah's witnesses beliefs regarding blood products stems from direct interpretation of passages from the bible. The use of crystalloid, starch products such as Hetastarch and colloids are accepted. Typically Jehovah's witnesses will accept most medical treatment but refrain from the use of blood products including whole blood, packed red cells, platelets, white cells, or plasma. Any autologous transfusion, whether from the patient themself or donor directed, is forbidden. The use of cell-saver type processes is a matter of individual choice by the patient. The use of hemoglobin-based oxygen carriers are now accepted by many patients but it is important to respect the wishes of each individual patient. It is very important to discuss preoperatively with the patient and family their wishes and thoughts on what is acceptable to use. Many facilities have adoptedbloodless-surgery protocols and committees that definitively outline the measures that can be used and take into consideration the many ethical issues involved in taking care of these patients.In a diagnostic test, the proportion of individuals who are truly free of a designated disorder identified by the test is known asspecificity.sensitivity.accuracy.positive predictive value.negative predictive value.Specificity refers to the proportion of individuals who are truly free of the designated disorder who are so identified by the test. Sensitivity refers to the proportion of individuals who truly have the disorder who are so identified by the test. Positive predictive value refers to the proportion of individuals with a positive test who have the disorder. Negative predictive value refers to the proportion of individuals with a negative test who are free of the disorder.Accuracy is the overall ability to identify patients with the disorder (true positives) and without the disorder (true negatives) in the study population.An orthopaedic surgeon in his first year of practice is negotiating with a private for-profit hospital to be their employed trauma specialist. The state of employment is known to have a high rate of malpractice claims because of a favorable plaintiff legal environment. During the course of negotiations, malpractice insurance is being discussed. The surgeon should ask the hospital to provide which type of malpractice insurance policy?Claims made with "nose" coverageClaims made without tail coverageNo policy because of employed status and sovereign immunityOccurrence coverageOccurrence coverage with "nose" coverageAn occurrence policy provides coverage for all claims made during employment irrespective of when it is filed (during or postemployment) and therefore is the best option. Claims made policy only covers suits for the time employed. A prepurchased "tail" is needed to provide coverage for cases that occurred during employment but filed postemployment. Nose coverage is applicable if the surgeon was previously employed and did not have tail coverage from previous employment, but this surgeon just emerged from training where it is not applicable. Claims made without tail coverage is unwise because the surgeon would be unprotected or have to purchase his own policy postemployment.Only in certain situations does sovereign immunity exist, and generally not in a for-profit system. Occurrence coverage with nose coverageis incorrect because it does not apply to this surgeon with no previous employment or claims policy lacking tail coverage.Results of a study demonstrating no difference between treatments when a difference truly exists is an example of which of the following?Statistical insignificanceType I errorType II errorFragile p-valuesNegative predictive valueA type II error (also known as a beta error) occurs when results demonstrate that two groups are similar when, in reality, they are different (with regard to the statistic being measured). Type I errors show that a difference exists when, in reality, no difference exists. A statistically insignificant result may lead an investigator to conclude that no difference exists between two groups; this may be correct (and therefore not a type II error). The concept offragilep-values is that small sample sizes may result in wide variability of p- values with only one change in a data point for a given group. This singular change could be a chance occurrence, but it still can affect the statistical significance of the outcomes analysis.Fragility of p-values is limited by increasing sample sizes. Negative predictive value is theproportion of patients with negative test results who are correctly diagnosed.A patient with a transverse femur fracture undergoes statically locked antegrade intramedullary nailing. Postoperatively, the patient appears to have a rotational deformity of greater than 25 degrees. The surgeon informs the patient, who chooses to undergo corrective treatment with removal of distal interlocking screws, rotational correction, and relocking of the screws. The patient goes on to healbut has persistent hip pain and a limp that does not improve completely after extensive rehabilitation. There is complete healing, no evidence of infection, no hardware issues, no ectopic bone, and rotational studies indicate less than 2 degrees of malrotation. Functional capacity testing reveals the affected abductor and quadriceps function to be about 85% of the uninjured side and the patient returns to work and most of his recreational activities except rock climbing. Two days before the statute of limitations, the patientfiles a malpractice suit alleging negligence of surgery, loss of function, consortium, and pain and suffering due to the surgeon's efforts. What action should the surgeon and the defense team take?Settle the case because the surgeon made an error that resulted in unnecessary surgery, and thus the case is indefensible.Settle the case because they are likely to lose the case, and it would be cheaper to settle than to defend.Defend the case alleging that there was no error, and no damages, and that the patient is malingering.Defend the case because despite there being an error, the error was corrected and there were little or no damages compared with expected outcomes.Contact the patient directly to discuss why he is suing and attempt an amicable resolution.To establish negligence, certain criteria must be met. 1) A duty was owed by the surgeon (in this case, yes, a relationship was established). 2) The duty was breached, where the provider failed to meet the standard of care (therewas a technical error, but it was corrected). 3) The breach caused an injury. In this case, the patient had an outcome that was very acceptable, asdocumented with outcome studies, for femur fractures. Also, the rotational error and locking distally would have had little impact on the hip, whereas antegrade nailing itself is expected to result in some objective impairment of the hip in some patients. 4) Damages were incurred as a result. In this case, the patient returned to work and could not rock climb which could be reasonably expected with a femur fracture in some patients, and cannot be causally linked to the corrective surgery. For all practical purposes, the patient had a very acceptable outcome. Thus, settling the case for an error would be rather permissive and the important issue is that the surgeon recognized the problem, addressed it, and fulfilled his or her postoperative responsibility. The case is very defendable, and thus it is unlikely to be lost. Defending the case and alleging no error is incorrect because there was an error. The surgeon should never function outside of his or her legal counsel once a suit is filed.You design a research study in which you ask patients who have a nonunion of the tibia to fill out a questionnaire in which they report on a variety of medical conditions and social/behavioral practices. You compare these findings to a similar group who did not develop a nonunion in order to identify medical and/or social conditions that might be risk factors for the development of tibial nonunions. This would be an example of what type of study?Case seriesMeta-analysisCase control studyRetrospective cohort studyProspective cohort studyA case control series starts with the occurrence of a specific disease or observation, and then compares data on those individuals to a similar group without the disease (control group) in order to identify potential risk factors for the development of the disorder. A case series is an observational study in which an investigator follows a series of patients who received a specific treatment, recording the results and outcomes of that treatment. A meta- analysis is the combination of several separate studies that look at similar hypotheses in an effort to create a larger patient population for analysis. A cohort study looks for the incidence of a specific outcome in two groups (cohorts) of patients who are similar with the exception of a particularresearch variable (risk factor).Which gene or protein is the most specific marker of mature osteoblasts but is not expressed by immature, proliferating osteoblasts?OsteocalcinTGF-BCOLIIA1cFOSIL-1Osteocalcin is the most specific marker of the osteoblast phenotype and is expressed only in mature osteoblasts. TGF-B is a growth factor involved in the differentiation of multiple cell lines. For bone, TGF-B plays a role in stem cell differentiation into mesenchymal stem cells along osteoblast pathways. COLIIA1 is the gene for Type II Collagen and is involved in chondrocyte differentiation. cFOS is involved in osteoclast differentiation. In regards tobone metabolism, IL-1 stimualtes osteoclastic bone resorption.A workers' compensation carrier for a local manufacturing company requests a second opinion on a 59-year-old man who sustained a crush injury to his foot and leg at work 6 months ago. His leg and foot were pinned between a forklift and a wall when an employee he was supervising lost control of the forklift. The employersuspects that the injured worker is malingering because the treating physician released him to work, but he has not returned to work. Which of the following elements of your history will best help you determine that the injured worker does not want to return to work out of fear of a confrontation with the employee he was supervising?FormalityEmpathyYes-no questionsTaking copious notesSitting leaning back in a chairEmpathy during the interview demonstrates compassion and earns the patient's trust; which, in turn, enables the patient to discuss any agenda or concerns he or she may otherwise feel uncomfortable revealing. It is also important to engage the patient to establish a trusting relationship and thus understand all the factors impacting the patient. A formal attitude toward the patient makes it difficult to engage the patient to be "drawn in." An engaged patient is more comfortable, reliable, and thorough when providing a history. Closed-end, yes-no questions do not allow the patient to detail all of the subtle nuances of their condition and its effect on their life. Taking copious notes likewise prevents engagement of the patient and the distraction of takingnotes may cause the physician to miss an important detail. It is better to lean forward in a chair when interviewing a patient because this suggests the physician is genuinely interested, whereas leaning back in a chair suggests the physician is simply waiting for the patient to finish talking. Avoid interrupting the patient when talking.When a Workers' Compensation patient recovers after an injury to a point that further restoration of function is no longer anticipated, he or she is said to have reached which of the following?Functional capacityMaximum medical improvementPermanent disabilityImpairment ratingPredesignationThis is the definition of maximum medical improvement (MMI). The patient has essentially reached the plateau of his improvement.Functional capacity evaluations (FCE) are based upon a theoretical model of comparing job demands to worker capabilities. The results of FCEs are often used to determine musculoskeletal capacity to return to work.Strong et al. reported on the use of FCE in the Workers' Compensation system, and note how these FCE results are required by employers to determine the level of return to work of their employees. They also mention that the reports are frequently perceived with a negative tone. The employees reported a wider range of restrictions in their varied life roles than did the FCE reports, which deal more narrowly with work roles.Pransky et al. reported that although FCE's are relied upon for determination of ability to perform physical work, several scientific, legal, and practical concerns persist. They note that test criteria often do not accurately reflect real-life job requirements or performance, and subjective evaluation remains common. They conclude that more research into predictive linking of FCE outcomes with occupational outcomes is necessary to determine their role in the Workers' Compensation system.Incorrect Answers:1: A functional capacity evaluation (FCE) is set of tests, practices and observations that are combined to determine the ability of the evaluated to function in a variety of circumstances (most often employment) in an objective manner.3: Permanent disability is any lasting disability that results in a reduced earning capacity after maximum medical improvement is reached; this implies that MMI must be reached before this is determined.4: Impairment rating is an objective data point obtained by a physician reviewing the patient's overall condition during a functional capacity evaluation.5: This is the process a patient uses to tell their employer they want a personal physician to treat them for a work injury.A physician receives a summons that he is being sued. The first step should be tocall the patient and apologize.notify the medical liability carrier.contact an attorney with whom the physician is familiar with and have the attorney review the records.be sure to discard any handwritten phone messages because they are not discoverable.find a colleague with a similar subspecialty and have the colleague review the record before doing anything.The most appropriate first step is to notify the medical liability carrier. The medical liability carrier will assign an attorney who is likely to be more appropriate. A review by a colleague may be requested by the defense attorney but that should be at their discretion. Patient apology is appropriate early on when and if you discover an error.Records should be reviewed, but never altered.Currently, what is the most common clinical study type in the orthopaedic literature?Level 1 (prospective, randomized trial)Level 2 (cohort trial)Level 3 (retrospective case control)Level 4 (retrospective case series)Level 5 (expert opinion)Although a recent push for prospective, randomized trials has been advocated by multiple orthopaedic journals, many studies published continue to be of Level 4 evidence (retrospective case series). Case series represented 64% of all studies reviewed by Freedman and associates in 2001 from the British and American volumes of Journal of Bone and Joint Surgery and from Clinical Orthopaedics and Related Research.Obremskey and associates published that

Bisphosphonates are a class of drugs that act to inhibit osteoclast resorption of bone. It has been shown that patients with multiple myeloma who are treated with bisphosphonates have fewer pathologic fractures than patients who are not treated with bisphosphonates. Vitamin D and calcium are considered appropriate for patients who are at risk for the development of osteoporosis, as is estrogen in selected women. Chelating agents and progesterones have no use in the treatment of patients with multiple myeloma or osteoporosis.

A decrease in tissue non-specific alkaline phosphatase (TNSALP) is found in hypophosphatasia. TNSALP is found in osteoblasts and hydrolyzes inorganic phosphates, leading to an increase in serum phosphate levels, which helps to maintain physiologic levels. A decrease in this process impairs bone mineralization leading to rickets. In the perinatal period, hypophosphatasia and decreased mineralization leads to caput membraneceum, shortened limbs and respiratory failure. Childhood hypophosphatasia is marked by premature loss of deciduous teeth and rachitic deformities. Adult hypophosphatasia is characterized by teeth and chest wall deformities as well as recurrent metatarsal and femoral stress fractures.

By WHO classification, her findings (T-score of -0.7SD) would merit a diagnosis of Normal bone mineral density (BMD).The WHO classifies bone density in postmenopausal women based on T-scores. Patients are classified based on the lowest T score of the spine, femoral neck, trochanter, or total hip. The classification should not be used with peripheral measurements. Z-scores are used for premenopausal women, younger men, and in children. The Z score compares a patient with age-, sex-, and race-matched norms.Blake and Fogelman reviewed the role of central DEXA in treatment of osteoporosis, compared with quantitative CT, peripheral DEXA and quantitative ultrasound. The advantages of central DEXA include results that can be interpreted using WHO T-score definitions, ability to predict fracture risk, and effectiveness at targeting antifracture treatments.Templeton reviewed secondary osteoporosis. In women with osteoporosis, the most common causes of secondary osteoporosis include hypercalciuria, malabsorption, hyperparathyroidism, vitamin D deficiency, and exogenous hyperthyroidism. In men with osteoporosis, the most common causes of secondary osteoporosis include hypogonadism, corticosteroid use and alcoholism.Unnanuntana et al. reviewed the assessment of fracture risk. The 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. They alsodiscussed 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.Illustration A shows the WHO classification. Illustration B shows a comparison between central DEXA and other methods of BMD measurement.Incorrect Answers:

Osteocyte cell processes travel through canaliculi to interconnect with other osteocytes and cells on the bone surfaces. Osteoblasts are cells that produce bone matrix and are seen rimming immature bone. Osteoclasts are large multinucleated cells that resorb bone and are found in Howship's lacunae. Megakaryocytes and histiocytes are found in marrow but not mature bone cortex.

There are many causes of rickets and osteomalacia. Renal osteodystrophy is a common complication of chronic renal failure and is one of the most common causes of osteomalacia. Pure osteomalacia is caused by the aluminum in phosphate binders used to treat hyperphosphatemia in renal failure. Desferoxamine is an effective chelator of aluminum in patients with biopsy documented aluminum-associated osteomalacia. Pure osteomalacia also can be caused by hypophosphatemia. The other choices are part of the mechanism of bone changes in renal osteodystrophy.

Induction coupling stimulates bone growth by increasing expression of BMP7, BMP2, TGF-beta1, and by increasing osteoblast proliferation. Induction coupling has not been shown to have the effect of decreasing osteoclast differentiation.

Acute Charcot neuroarthropathy is driven by a localized inflammatory response marked by elevated pro-inflammatory cytokines (e.g., TNF-alpha, IL-1beta, IL-6). These cytokines powerfully stimulate the Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) pathway, shifting the balance away from osteoprotegerin (OPG) and leading to unchecked osteoclastogenesis and aggressive bone resorption. This osteolysis characterizes Eichenholtz stage I (development/fragmentation phase).

The patient is exhibiting signs of an impending atypical femur fracture (AFF) associated with long-term bisphosphonate use. Because she is symptomatic (thigh pain) and has radiographic evidence of an incomplete fracture (radiolucent line/lateral spiking), prophylactic intramedullary nailing is indicated to prevent completion.

The patient has MRI findings throughout her lumbar spine consistent with old compression fractures. Given the imaging findings and advanced age, she is at high risk for osteoporosis and subsequent fragility fractures. Management should consist of a DEXA scan to evaluate her degree of osteoporosis and begin medical treatment as appropriate. Because acute fracture is unlikely, and she has no neurologic compromise, neither bracing nor surgical treatment is indicated.

Callus formation is biomechanically benefecial because it increases the outer diameter of the bone, leading to an increase in stiffness, torsional strength, moment of inertia, and decreases resultant interfragmentary strain at the fracture site.The biomechanical role of the peripheral callus is to provide initial stability to the fracture and to act as a scaffold for gradual mineralization. Because the bending stiffness of a structure is proportional to the 4th power of the diameter, a peripherally located callus provides substantial stability to the fracture, despite the relatively low stiffness and strength of callus. For example, doubling the diameter of the callus increases the resistance to bending by a factor of 16. As mineralization progresses, the bending stiffness and strength of the healed fracture eventually may be substantially greater than that of the original, intact bone.Augat et al. review the mechanical and biological aspects of fracture healing. They report that increased diameter of periosteal callus formation benefits healing by enlarging the cross-sectional area of area of the bridging tissue and reducing interfragmentary motion. Patients with osteoporosis are known to have decreased callus mineralization and biomechanical properties.Incorrect Answers:

DISCUSSION: The radiographs demonstrate a rapid erosion of the bipolar component into the acetabulum. Although acetabular erosion is more common with unipolar hip arthroplasties, it can occur with bipolar components. Haidukewych and associates noted a very low erosion rate but none in the first 2 years. The second finding on the radiographs is the linear radiolucency progressing from the joint toward the end of the stem at the cement-bone interface suggesting chronic infection or diffuse loosening. The persistent pain since implantation also suggests chronic infection. High activity levels and osteoporosis do not lead to acetabular erosion in the first 2 years after hemiarthroplasty. While the cement technique is suboptimal, loosening and erosion should not be expected from this alone. An oversized bipolar head would extrude and not erode.

Hypophosphatemia-The patients who were symptomatic had obtundation,hemolytic anemia, rhabdomyolysis, and hepatocellular injury that began during refeeding and resolved with treatment. The signs and symptoms, pathophysiology, and treatment of refeeding hypophosphatemia are reviewed.Renal Osteodystrophy-Musculoskeletal complications in patients with chronic renal failure are common and may be related to the disease itself or to treatment. The altered metabolism in patients with chronic renal failure leads to renal osteodystrophy, which consists of osteomalacia and secondary hyperparathyroidism [1]. Erosive changes attributable to secondary hyperparathyroidism may be easily confused with rheumatoid arthritis, seronegative spondyloarthropathies, infection, or even malignancy.Primary Hyperparathyroidism-Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean.Skeletal disease in primary hyperparathyroidism J Bone Miner Res 1989 Jun; 4(3):283-91Nutritional vitamin D deficiency-Rickets, osteomalacia, and renal osteodystrophy are disorders of the mineralization of bone that result from a lack of available calcium, phosphorus, or both. The diseases that result from numerous mechanisms present with a symptom-sign-radiographic complex with such a high degree of stereotypy that laboratory investigation is often required to distinguish one form from another. The disorders in children, known as rickets, produce bowing and other deformities of the long bones and dwarfism. These disorders are principally related to the profound effect of the deficiency states on the epiphyseal plate; whereas the same disorders in adults produce an often severe osteopenia and pathologic fractures. Because of newer developments in our understanding of the factors affecting calcium-phosphorushemostasis and vitamin D metabolism, many of the children and Rickets, osteomalacia, and renal osteodystrophy.

Denosumab is a monoclonal antibody that targets and inhibits RANKL binding to the RANK receptor, which is found on osteoclasts. As a result, it inhibits activation of osteoclast cells and slows the process of bone resorption and bone turnover via osteoclast inhibition. The end result is similar to bisphosphonates in terms of effector cell, but the mechanism of action is very different. RANKL binds to RANK, but OPG inhibits RANK binding to RANKL. TNF is an inflammatory cytokine, and monoclonal antibodies to TNF are used to treat systemic inflammatory disease such as rheumatoid arthritis.

DISCUSSION: In an atrophic nonunion with a good soft-tissue envelope, adequate plating with cancellous bone graft can be used to span defects of up to 6 cm.  Cortical graft from the fibula or iliac crest is not necessary.  BMP-7 is a bone graft substitute and should not be used alone in this patient because the hardware is loose.REFERENCES: Ring D, Allende C, Jafarnia K, et al: Ununited diaphyseal forearm fractures with segmental defects: Plate fixation and autogenous cancellous bone-grafting.  J Bone Joint Surg Am 2004;86:2440-2445.

DISCUSSION: Histologic studies have shown that increased bone turnover is the rule in OI.  Pamidronate (and all bisphosphonates) reduce osteoclast-mediated bone resorption.  Osteoblastic new bone formation on the periosteal surface of long bones is minimally impaired.  With inhibition of osteoclastic bone resorption on the endosteal surface, the cortex of the bone can begin to thicken as it does with normal growth in individuals unaffected by OI.  Mineralization and collagen matrix organization are not directly affected by pamidronate.REFERENCES: Zeitlin L, Fassier F, Glorieux FH: Modern approach to children with osteogenesis imperfecta.  J Pediatr Orthop B 2003;12:77-87.Falk MJ, Heeger S, Lynch KA, et al: Intravenous bisphosphonate therapy in children with osteogenesis imperfecta.  Pediatrics 2003;111:573-578.Glorieux FH, Bishop NJ, Plotkin H, et al: Cyclic administration of pamidronate in children with severe osteogenesis imperfecta.  N Engl J Med 1998;339:947-952.