Orthopedic Basic MCQs 2026 | Board Review & Answers

Question 1

A 30-year-old woman has pain in her right hand. The radiograph, CT scan, and biopsy specimen are seen in Figures 38a through 38c. What is the most likely diagnosis?

Explanation

38b 38c An enchondroma is the most common primary tumor of the long bones of the hand. The lesion is usually asymptomatic and often is detected when there is a pathologic fracture. Shimizu K, Kotoura Y, Nishijima N, Nakamura T: Enchondroma of the distal phalanx of the hand. J Bone Joint Surg Am 1997;79:898-900.

Question 2

Which of the following agents have been shown to reduce the incidence of skeletal events in patients with multiple myeloma?

Explanation

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. Berenson JR: Bisphosphonates in multiple myeloma. Cancer 1997;15:1661-1667.

Question 3

A 12-year-old girl has had progressive left knee pain for the past 4 months. She reports that the pain is unrelated to activity, and she has no history of fever or recent infections. Examination reveals full range of motion of the knee but tenderness along the medial joint line. Plain radiographs and MRI scans are shown in Figures 39a through 39d. A biopsy specimen of the lesion is shown in Figure 39e. Treatment should include

Explanation

39b 39c 39d 39e The lesion is a chondroblastoma. The plain radiographs show a well-defined radiolucent lesion in the distal femoral epiphysis of a skeletally immature patient. The margins are well defined, suggesting a benign growth. The epiphysis is an unusual location for bone tumors, except for chondroblastomas. Of all chondroblastomas, 95% are located within the epiphysis. The MRI scans show a punctate appearance that is commonly seen in cartilage lesions. The biopsy specimen shows a chondroid lesion with polygonal chondrocytes. These findings are consistent with a chondroblastoma. The natural history of chondroblastomas is for continued growth and bone destruction if left untreated. Treatment should consist of curettage, with or without the use of physical or chemical adjuvants, and bone grafting.

Question 4

An open biopsy specimen of a radiodense distal clavicle lesion in a 12-year-old girl shows chronic polyclonal inflammatory cells without granuloma formation. Laboratory studies show that bacterial, fungal, and acid-fast bacillus cultures are negative. Subsequently, a similar lesion is noted in the fibula. The next most appropriate step in management should consist of

Explanation

The most likely diagnosis is chronic multifocal osteomyelitis. This is a culture-negative polyostotic disease that is most commonly found in young people. The treatment of choice is anti-inflammatory drugs. The pathology does not suggest eosinophilic granuloma. Antiviral therapy, broad-spectrum antibiotics, and surgical resection are not indicated for this disease.

Question 5

Figure 40 shows the radiograph of a 30-year-old woman who has a painful elbow. Examination reveals a deformed skull, multiple cafe-au-lait spots, and bone deformities. What is the most likely diagnosis?

Explanation

Findings in patients with McCune-Albright syndrome include polyostotic fibrous dysplasia, multiple cafe-au-lait spots, and precocious puberty. The bone changes in NF-1 resemble nonossifying fibromas, not fibrous dysplasia. NF-2 has little bony change with typical ocular abnormalities. Paget's disease occurs in older individuals and does not present with cafe-au-lait spots. Ollier's disease (multiple enchondromatosis) may show bone changes but not the other findings. Albright F, Butler AM, Hampton AO, et al: Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction with precocious puberty in females. N Engl J Med 1937;216:727-746. Danon M, Robboy SJ, Kim S, Scully R, Crawford JD: Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy. J Pediatr 1975;87:917-921.

Question 6

Figure 41a shows the AP radiograph of a 15-year-old boy who reports lateral knee pain. Figures 41b and 41c show a radiograph of the distal femur that was obtained 5 years ago and a current CT scan. The indication for surgery in this patient would be

Explanation

41b 41c In a young person with solitary osteochondroma, the best surgical indication is symptoms that limit activity. A growth deformity is unlikely to occur at this age. Malignant degeneration is exceptionally rare and noted most commonly in adults. Growth is expected until skeletal maturity. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989, pp 1626-1659.

Question 7

In what decade does the peak incidence of conventional osteosarcoma occur?

Explanation

Conventional osteosarcoma most frequently occurs in the second decade, followed by the third decade. Approximately 70% to 75% of patients with osteosarcoma are between the ages of 10 and 25 years. Secondary osteosarcoma (arising in Paget's disease or radiation-induced) is seen in older adults. Simon MA, Springfield DS, et al: Osteogenic Sarcoma: Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott Raven, 1998, p 266. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989.

Question 8

A 10-year-old boy has a painful thigh mass. A radiograph, MRI scan, and biopsy specimen are shown in Figures 42a through 42c. What is the most likely diagnosis?

Explanation

42b 42c A destructive mixed lytic and blastic metaphyseal lesion with a large soft-tissue mass in an adolescent is most likely an osteosarcoma until proven otherwise. The epicenter of the tumor is on the surface of the bone, most likely involves the periosteum, and is more likely to be chondroblastic in nature. Parosteal osteosarcoma is a low-grade tumor, much more radiodense, usually smaller, and found in the posterior distal femur of middle-aged patients. Chondrosarcomas are distinctly rare in childhood.

Question 9

A 21-year-old man with neurofibromatosis and multiple cutaneous neurofibromas has a rapidly enlarging painless mass on his buttock. Examination reveals a nontender, well-defined 6- x 6-cm soft-tissue mass that is deep to the fascia. The best course of action should be to order

Explanation

Patients with neurofibromatosis are at risk for development of soft-tissue sarcomas (most commonly malignant peripheral nerve sheath tumors). Clinical indications of development of a neurofibrosarcoma include a rapidly enlarging soft-tissue mass; therefore, this patient should be considered to have a neurofibrosarcoma until proven otherwise. MRI is superior to CT in characterizing the anatomic location of soft-tissue masses and the signal characteristics of the lesion. Areas of necrosis within the tumor may be apparent on MRI that cannot be appreciated on CT, suggesting a malignant tumor. Local imaging studies of suspected malignant tumors should be performed prior to needle or open biopsy so that the biopsy site can be excised at the time of definitive resection. Additionally, postbiopsy changes may lead to MRI artifacts that alter the interpretation of the MRI. Demas BE, Heelan RT, Lane J, Marcove R, Hajdu S, Brennan MF: Soft-tissue sarcomas of the extremities: Comparison of MR and CT in determining the extent of disease. Am J Roentgenol 1988;150:615-620.

Question 10

A 21-year-old man has had progressive right knee pain for the past 2 months that is exacerbated with weight-bearing activities. A plain radiograph and an MRI scan are shown in Figures 43a and 43b. A biopsy specimen is shown in Figure 43c. According to the Enneking staging system of tumor classification, the lesion should be classified as what stage?

Explanation

43b 43c The lesion is an eccentric lytic bone lesion within the epiphyseal-metaphyseal end of the proximal tibia. There is geographic destruction with a "fading border" extending to the articular cartilage. There is no matrix formation or periosteal reaction. The MRI scan shows cortical destruction with extension into the soft tissue. According to the Enneking staging system, benign lesions are stage 1, 2, or 3; malignant lesions are stage I, II, or III. Benign stage 1 lesions are latent; stage 2 are active; and stage 3 are benign aggressive. The histology shows a benign giant cell tumor. Given the cortical breakthrough shown on the MRI scan, the lesion should be classified as stage 3. Enneking WF: Clinical musculoskeletal pathology, in Enneking WF (ed): Appendix A. Gainesville, FL, Storter Publishing, 1986, pp 451-466.

Question 11

What is a common clinical finding in patients with severe hypercalcemia secondary to bony metastasis?

Explanation

Increased levels of calcium are known to cause anorexia, nausea, vomiting, dehydration, muscle weakness, polyuria, and polydipsia. Treatment may include hydration, saline diuresis, and bisphosphonates.

Question 12

What cell type causes the bone destruction in metastatic lesions?

Explanation

The main consequence of tumor invading the bone is activation of both osteoblasts and osteoclasts. However, the osteoclastic effect predominates in the majority of tumors early after the invasion of bone by tumor cells, causing resorption of bone. Cramer SF, Fried L, Carter KJ: The cellular basis of metastatic bone disease in patients with lung cancer. Cancer 1981;48:2649-2660.

Question 13

What is the most common malignant bone tumor seen in patients with multiple hereditary exostosis?

Explanation

Secondary chondrosarcomas are most common in patients with multiple hereditary exostosis. Dedifferentiated chondrosarcoma is less common and refers to bone lesions in which a high-grade spindle cell sarcoma component is located immediately adjacent to a low-grade cartilage neoplasm. Mesenchymal chondrosarcoma, clear cell chondrosarcoma, and periosteal osteosarcoma are no more common in patients with multiple hereditary exostosis than in the general population. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989, pp 1660-1669.

Question 14

An athletic 55-year-old man reports a painless mass in the anterior aspect of the thigh that appeared 3 weeks ago and has not changed in size. The patient denies any history of trauma. Examination reveals a firm, well-defined nontender mass in the anterior thigh and no inguinal adenopathy or cutaneous changes. Plain radiographs are unremarkable. T1- and T2-weighted MRI scans are shown in Figures 44a and 44b. What is the most likely diagnosis?

Explanation

44b The presence of a painless soft-tissue mass that is greater than 5 cm and deep to the fascia should be considered a soft-tissue sarcoma until proven otherwise. The diagnosis of a hematoma should be made with great caution because the absence of a history of trauma, pain, or presence of ecchymosis makes it unlikely. A diagnosis of pyomyositis is unlikely because of the absence of warmth, erythema, or adenopathy. The MRI scans are not consistent with lipoma or hemangioma. The MRI signal characteristics of a lipoma should be the same as subcutaneous fat on all sequences. Soft-tissue hemangiomas are not well defined and have an infiltrative appearance on MRI scans, as does pyomyositis. Sim FH, Frassica FJ, Frassica DA: Soft-tissue tumors: Diagnosis, evaluation and management. J Am Acad Orthop Surg 1994;2:202-211.

Question 15

Epithelioid sarcoma most commonly occurs in which of the following anatomic locations?

Explanation

Epithelioid sarcoma is a rare soft-tissue sarcoma that most commonly arises in the hand or upper extremity, and it is frequently misdiagnosed as an infection or granuloma. It tends to have a higher incidence of lymph node metastasis than other soft-tissue sarcomas. The mainstay of treatment is wide surgical excision, even if amputation is necessary. Gupta TD, Chaudhuri P (eds): Tumors of the Soft Tissues, ed 2. Stamford, CT, Appleton and Lange, 1998, p 475.

Question 16

What common cytologic abnormality is associated with Ewing's sarcoma?

Explanation

Cytogenetic abnormalities have been well characterized in a number of tumors. Translocation t (2, 13), (x, 18), (12, 16), and (12, 22) have been characterized in rhabdomyosarcoma, synovial cell sarcoma, myxoid liposarcoma, and clear cell sarcoma, respectively. Translocation t(11:22) can be identified in 95% of patients with Ewing's sarcoma. This was first described by Turc-Carel and associates in 1984. Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 3. St Louis, MO, Mosby Year Book, 1995, pp 105-118. Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM: Chromosome study of Ewing's sarcoma (ES) cell lines: Consistency of a reciprocal translocation t(11;22) (q24;q12). Cancer Genet Cytogenet 1984;12:1-19.

Question 17

Figures 45a and 45b show the radiographs of a 46-year-old man who reports the acute onset of right knee pain and is unable to bear weight on the extremity. His medical history is unremarkable. The next most appropriate step in management should consist of

Explanation

45b The patient has a pathologic fracture of the right distal femur; therefore, given the patient's age, the most likely diagnosis is metastatic carcinoma. Staging studies should be obtained prior to surgical treatment. Immediate intramedullary fixation is contraindicated before a diagnosis is made by biopsy. Surgical stabilization should be performed prior to radiation therapy.

Question 18

Figure 46 shows the MRI scan of a patient who has a mass in the calf that has been fluctuating in size. Radiographs are negative. Which of the following procedures will most quickly aid in confirming the diagnosis?

Explanation

The bright signal on the T2-weighted MRI scan suggests fluid. The multiloculated appearance in proximity to the proximal tibiofibular joint suggests that the most likely diagnosis is a ganglion. They typically increase and decrease in size and can be diagnosed by the classic gelatinous fluid obtained through needle aspiration. Bianchi S, Abdelwahab IF, Kenan S, Zwass A, Ricci G, Palomba G: Intramuscular ganglia arising from the superior tibiofibular joint: CT and MR evaluation. Skeletal Radiol 1995;24:253-256.

Question 19

What are the five most common tumors that metastasize to bone?

Explanation

The five most common primary carcinomas that metastasize to bone are breast, prostate, lung, renal, and thyroid in decreasing order of incidence. Frassica FJ, Gitelis S, Sim FH: Metastatic bone disease: General principles, pathophysiology, evaluation, and biopsy. Instr Course Lect 1992;41:293-300.

Question 20

Pain associated with a proximal medial tibial osteochondroma in a 10-year-old patient is most commonly the result of

Explanation

Pain secondary to an osteochondroma is usually from soft-tissue irritation and bursal formation. This is particularly common for proximal medial tibia osteochondromas that irritate the pes anserine tendons. Malignant degeneration into a chondrosarcoma rarely occurs, is usually associated with multiple hereditary exostoses, and usually occurs after skeletal maturity. Borges AM, Huvos AG, Smith J: Bursa formation and synovial chondrometaplasia associated with osteochondromas. Am J Clin Pathol 1981;75:648-653.

Question 21

Figures 47a through 47f show the AP radiograph, bone scan, CT scan, MRI scan, and biopsy specimens of a 30-year-old woman who has had vague left shoulder pain for 1 year. Management should consist of

Explanation

47b 47c 47d 47e 47f The histology shows eosinophils with a background of larger cells (Langerhans' cells). This is consistent with eosinophilic granuloma. Localized sites are best treated with curettage, steroid injection, or observation. Chemotherapy is used only if there is systemic involvement. Mirra JM: Eosinophilic granuloma, in Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. London, England, Lea and Febiger, 1989, pp 1023-1060. Sessa S, Sommelet D, Lascombes P, Prevot J: Treatment of Langerhans-cell histiocytosis in children: Experience at the Children's Hospital of Nancy. J Bone Joint Surg Am 1994;76:1513-1525.

Question 22

What is the 5-year overall survival rate for adults with high-grade soft-tissue sarcomas?

Explanation

The 5-year overall survival rate for deep, high-grade soft-tissue sarcomas is around 50%. The overall survival and disease-free survival rates chiefly depend on the tumor stage, but for all stages combined, most cancer treatment centers report a 5-year overall survival rate of around 70% and a disease-free survival rate of 65%. Fleming ID, et al: Manual for Staging of Cancer/American Joint Committee on Cancer, ed 5. Philadelphia, PA, Lippincott Raven, 1997, pp 149-156.

Question 23

Figures 48a through 48c show the lateral radiograph and MRI scans of a 60-year-old man who has had pain in his thigh for 1 month. The next most appropriate step in management should consist of

Explanation

48b 48c The patient has a presumed metastatic bone tumor. The approach to evaluating a patient with a bone tumor of unknown primary origin is to obtain laboratory studies that include a CBC, an erythrocyte sedimentation rate, a serum protein electrophoresis, a calcium level, a urinalysis, and a prostate-specific antigen. In addition, a bone scan, a radiograph of the chest, and CT scans of the chest and abdomen should be obtained. These evaluations can identify the primary site in 85% of patients. GI studies rarely are of diagnostic value. Prophylactic stabilization is contraindicated until a diagnosis is confirmed by histology. Frassica FJ, Frassica DA, McCarthy EF, Riley LH III: Metastatic bone disease: Evaluation, clinicopathologic features, biopsy, fracture risk, nonsurgical treatment, and supportive management. Instr Course Lect 2000;49:453-459.

Question 24

A 17-year-old boy has had a mass in his right thigh for the past 6 months. He denies any history of trauma. Examination reveals that the mass is painless and firm. A radiograph and axial MRI scan are shown in Figures 49a and 49b. What is the most likely diagnosis?

Explanation

49b Osteochondroma typically occurs as a bony projection or a sessile growth on the bone, and there can be flaring of the metaphysis. The radiograph shows continuity from the adjacent cancellous bone into the lesion itself. There is no soft-tissue mass or bone destruction to suggest osteosarcoma or Ewing's sarcoma. Periosteal chondroma has a scalloped out radiographic appearance. Chondroblastoma typically is an epiphyseal-based lesion.

Question 25

Evaluation of the percent of necrosis in the resected specimen after preoperative chemotherapy is of prognostic value for what type of sarcoma?

Explanation

To date, only the percent of necrosis after induction chemotherapy in high-grade osteosarcomas seems to be of prognostic value. The value in soft-tissue sarcoma and rhabdomyosarcoma is being evaluated but has not been substantiated. Chondrosarcomas and parosteal osteosarcomas are not treated with chemotherapy. Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG: Primary osteogenic sarcoma: The rationale for pre-operative chemotherapy and delayed surgery. Cancer 1979,43:2163-2177. Davis AM, Bell RS, Goodwin PJ: Prognostic factors in osteosarcoma: A critical review. J Clin Oncol 1994;12:423-431.

Question 26

Which of the following best describes the intracellular signaling pathway activated by Bone Morphogenetic Protein (BMP) to promote osteoblast differentiation?

Explanation

BMPs bind to serine/threonine kinase receptors, leading to the phosphorylation of Smad 1, 5, and 8. These form a complex with Smad 4 and translocate to the nucleus to regulate gene expression for osteoblast differentiation.

Question 27

A 14-year-old boy with multiple palpable bone masses presents for evaluation. Radiographs reveal multiple pedunculated and sessile osteochondromas. A mutation in the EXT1 gene is suspected. This gene mutation primarily affects which of the following processes?

Explanation

Multiple hereditary exostoses is caused by mutations in the EXT1 or EXT2 genes. These genes encode glycosyltransferases essential for the synthesis of heparan sulfate, leading to abnormal chondrocyte proliferation.

Question 28

A 65-year-old woman with metastatic breast cancer is treated with an agent to prevent skeletal-related events. The agent is a monoclonal antibody that targets RANKL. Which of the following is the primary cellular effect of this medication?

Explanation

Denosumab is a monoclonal antibody that binds to RANKL, preventing it from binding to RANK on osteoclasts and their precursors. This inhibits osteoclast formation, function, and survival, thereby reducing bone resorption.

Question 29

An infant presents with multiple fractures, cranial nerve palsies, and diffuse osteosclerosis on radiographs. A diagnosis of malignant infantile osteopetrosis is made. The most common genetic mutation associated with this condition affects which of the following osteoclast functions?

Explanation

Malignant infantile osteopetrosis is most commonly caused by mutations in the TCIRG1 gene, which encodes a subunit of the osteoclast vacuolar proton pump (V-ATPase). This defect impairs acid secretion at the ruffled border, preventing bone resorption.

Question 30

A 32-year-old man presents with a slow-growing, painful mass in his left thigh. MRI shows a well-circumscribed soft tissue mass adjacent to the knee joint. Biopsy reveals a biphasic tumor with both epithelial and spindle cell components. Which of the following chromosomal translocations is diagnostic for this lesion?

Explanation

Synovial sarcoma is characterized by the t(X;18) chromosomal translocation, which fuses the SYT gene on chromosome 18 with the SSX1, SSX2, or SSX4 gene on the X chromosome.

Question 31

A 40-year-old man presents with chronic shoulder pain. Radiographs reveal a lytic lesion with intralesional calcifications in the proximal humeral epiphysis. Biopsy shows malignant cells with abundant clear cytoplasm. Which of the following is true regarding this diagnosis?

Explanation

Clear cell chondrosarcoma is a rare, low-grade malignant bone tumor that characteristically arises in the epiphysis of long bones. It is treated with wide surgical resection, as it is relatively resistant to chemotherapy and radiation.

Question 32

A 6-year-old boy presents with refusal to walk, gingival bleeding, and petechiae. Radiographs of the lower extremities show osteopenia, a dense zone of provisional calcification, and an adjacent radiolucent band. The underlying nutritional deficiency impairs which of the following steps in collagen synthesis?

Explanation

Vitamin C deficiency (scurvy) impairs the activity of prolyl and lysyl hydroxylases, enzymes required for the hydroxylation of proline and lysine residues during collagen synthesis. This leads to weakened connective tissue and fragile blood vessels.

Question 33

In normal articular cartilage, which of the following zones contains the highest concentration of water and has collagen fibers oriented parallel to the joint surface?

Explanation

The superficial (tangential) zone of articular cartilage has the highest water content, the lowest proteoglycan concentration, and collagen fibers arranged parallel to the articular surface to resist shear forces.

Question 34

A 15-year-old boy presents with a permeative lytic lesion in the diaphysis of the femur with an associated "onion skin" periosteal reaction. Biopsy confirms Ewing sarcoma. Which of the following fusion proteins is most commonly associated with this tumor?

Explanation

Ewing sarcoma is most commonly associated with the t(11;22) translocation, resulting in the EWS-FLI1 fusion protein. This acts as an aberrant transcription factor driving oncogenesis.

Question 35

A 30-year-old woman presents with knee pain. Radiographs show an eccentric, lytic, epiphyseal lesion in the distal femur extending to the subchondral bone. Biopsy reveals multinucleated giant cells interspersed with mononuclear stromal cells. Which of the following cells expresses RANKL in this tumor?

Explanation

In a Giant Cell Tumor of bone, the neoplastic mononuclear stromal cells express RANKL. This recruits and activates the reactive multinucleated giant cells that cause the characteristic osteolytic bone destruction.

Question 36

Continuous administration of Parathyroid Hormone (PTH), as seen in primary hyperparathyroidism, leads to net bone resorption. Which of the following best describes the direct action of PTH on bone cells to induce this effect?

Explanation

Osteoclasts lack PTH receptors. PTH binds to receptors on osteoblasts and osteoprogenitor cells, stimulating them to increase the expression of RANKL and decrease the expression of Osteoprotegerin (OPG), which indirectly activates osteoclasts.

Question 37

A diaphyseal fracture is treated with rigid plate fixation and absolute stability, achieving a gap of less than 0.1 mm. Which of the following best describes the mechanism of bone healing expected in this scenario?

Explanation

Absolute stability with interfragmentary compression and a gap < 0.1 mm leads to primary (contact) bone healing. This occurs via direct remodeling by osteoclastic cutting cones followed by osteoblasts, without the formation of an intermediate fracture callus.

Question 38

In orthopedic implant metallurgy, mixing components made of 316L stainless steel and titanium alloys is generally avoided. Which of the following best explains the risk of combining these two different metals in vivo?

Explanation

Mixing dissimilar metals in an electrolytic environment can cause galvanic corrosion. The less noble metal (anode), in this case stainless steel, will undergo accelerated corrosion, potentially leading to implant failure or adverse tissue reactions.

Question 39

A 2-year-old child presents with bowing of the legs, alopecia, and hypocalcemia. Laboratory tests show elevated levels of 1,25-dihydroxyvitamin D and elevated parathyroid hormone. Which of the following is the most likely underlying defect?

Explanation

Vitamin D-dependent rickets type II is caused by an end-organ resistance to active vitamin D due to a mutation in the Vitamin D receptor. This leads to high levels of 1,25-dihydroxyvitamin D, hypocalcemia, and frequently alopecia.

Question 40

A patient presents with acute monoarticular knee swelling. A joint aspiration is performed. The synovial fluid has a leukocyte count of 75,000 cells/mm^3 with 90% polymorphonuclear cells. Which of the following is the most appropriate next step in management?

Explanation

A synovial fluid leukocyte count >50,000 cells/mm^3 with a predominance of PMNs is highly suspicious for septic arthritis. The gold standard treatment is urgent surgical irrigation and debridement along with empiric intravenous antibiotics.

Question 41

Which of the following enzymes is considered a primary driver of articular cartilage matrix degradation in the pathogenesis of osteoarthritis?

Explanation

Matrix metalloproteinases (MMPs), particularly MMP-13 (collagenase-3), play a central role in osteoarthritis by cleaving type II collagen, leading to the irreversible breakdown of the articular cartilage matrix.

Question 42

Which of the following is the most significant prognostic factor for survival in a patient with localized high-grade osteosarcoma following neoadjuvant chemotherapy?

Explanation

The percentage of tumor necrosis (histologic response) following neoadjuvant chemotherapy is the most critical prognostic indicator for overall survival in high-grade osteosarcoma. Greater than 90% necrosis is considered a good response.

Question 43

A 14-year-old boy presents with a painful mass in the diaphysis of his femur. Biopsy reveals uniform small round blue cells. Cytogenetic analysis of this tumor is most likely to show which of the following translocations?

Explanation

Ewing sarcoma is a small round blue cell tumor typically arising in the diaphysis of long bones. It is genetically characterized by the t(11;22) translocation, which results in the EWS-FLI1 fusion protein.

Question 44

In the medical management of an unresectable or recurrent giant cell tumor of bone, denosumab is frequently utilized. Which of the following best describes its primary mechanism of action?

Explanation

Denosumab is a monoclonal antibody that binds to Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL). This prevents RANKL from activating RANK on osteoclasts and their precursors, thereby profoundly inhibiting bone resorption.

Question 45

A 4-year-old child presents with multiple fractures and is found to have diffuse osteosclerosis and 'bone-in-bone' appearance on radiographs. Genetic testing reveals a mutation in the carbonic anhydrase II gene. This condition is primarily caused by a defect in which cellular process?

Explanation

Osteopetrosis caused by carbonic anhydrase II deficiency results in the inability of osteoclasts to acidify the clear zone (resorption pit). This leads to defective bone resorption and dense, brittle bones.

Question 46

A 28-year-old man presents with a slow-growing, deep-seated soft tissue mass near the knee joint. Biopsy shows a biphasic pattern of spindle and epithelial cells. Which molecular abnormality is diagnostic for this lesion?

Explanation

Synovial sarcoma classically presents as a deep soft tissue mass near a joint in a young adult. The pathognomonic molecular marker is the t(X;18) translocation, creating the SYT-SSX fusion gene.

Question 47

A 10-year-old girl is evaluated for a Shepherd's crook deformity of the proximal femur. Radiographs show a ground-glass appearance of the medullary canal. This condition is associated with a postzygotic somatic mutation in which of the following genes?

Explanation

Fibrous dysplasia is a developmental anomaly of bone caused by a somatic activating mutation in the GNAS gene. This leads to increased intracellular cAMP and impaired differentiation of bone-forming cells.

Question 48

A 6-year-old boy presents with progressive bowing of his lower extremities. Laboratory evaluation demonstrates a normal serum calcium, extremely low phosphorus, and elevated alkaline phosphatase. Which of the following is the most likely diagnosis?

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX mutation leading to elevated FGF-23, which results in severe renal phosphate wasting. Labs characteristically show low phosphorus, normal calcium, and elevated alkaline phosphatase.

Question 49

A 12-year-old girl has an expansile, eccentric lytic lesion in the proximal tibia. MRI reveals multiple fluid-fluid levels. Primary aneurysmal bone cysts are genetically characterized by a rearrangement involving which of the following genes?

Explanation

Primary aneurysmal bone cysts are considered true neoplasms driven by rearrangements of the USP6 gene on chromosome 17. This distinguishes them from secondary aneurysmal bone cysts, which lack this genetic mutation.

Question 50

A 19-year-old man complains of severe right thigh pain that is worse at night and dramatically relieved by ibuprofen. Radiographs show dense cortical thickening with a small radiolucent nidus. The intense pain associated with this lesion is mediated by high local concentrations of which substance?

Explanation

Osteoid osteomas produce exceptionally high levels of Prostaglandin E2 (PGE2) due to high expression of COX-2 within the tumor nidus. NSAIDs effectively relieve the pain by blocking this specific pathway.

Question 51

During the early stages of primary osteoarthritis, which of the following biochemical changes initially occurs in the articular cartilage matrix?

Explanation

Early osteoarthritis is characterized by cleavage of the superficial collagen network, allowing the hydrophilic proteoglycans to swell. This results in an overall increased water content and a subsequent relative decrease in proteoglycan concentration.

Question 52

A patient with severe dietary restrictions presents with bleeding gums, petechiae, and joint pain. Radiographs show osteopenia and a dense provisional zone of calcification. The underlying cellular defect involves failure of which step in collagen synthesis?

Explanation

Scurvy is caused by Vitamin C deficiency, a necessary cofactor for prolyl and lysyl hydroxylases. Without proper intracellular hydroxylation of proline and lysine, stable collagen triple helices cannot form.

Question 53

Parathyroid hormone (PTH) regulates serum calcium levels by eventually stimulating bone resorption. Which of the following cells does PTH directly bind to in order to initiate this resorptive cascade?

Explanation

Osteoclasts do not have PTH receptors; rather, PTH binds directly to receptors on osteoblasts. This stimulates osteoblasts to increase RANKL expression, which secondarily activates osteoclasts to resorb bone.

Question 54

In the pathogenesis of rheumatoid arthritis, joint destruction is primarily mediated by the hyperplastic synovium (pannus). Which of the following cells within the pannus is the major source of the destructive matrix metalloproteinases?

Explanation

Fibroblast-like synoviocytes in the hyperplastic pannus are the primary producers of matrix metalloproteinases (MMPs) and cathepsins. These enzymes directly mediate the degradation of the articular cartilage.

Question 55

Romosozumab, an agent used for the treatment of severe osteoporosis, exerts its anabolic effect on bone by directly binding and inhibiting which of the following molecules?

Explanation

Romosozumab is a monoclonal antibody that targets and inhibits sclerostin, a glycoprotein produced by osteocytes. Blocking sclerostin disinhibits the Wnt/beta-catenin signaling pathway in osteoblasts, robustly promoting bone formation.

Question 56

A 55-year-old man presents with a painful mass in the proximal humerus. Radiographs show a large lytic lesion with intralesional "popcorn" calcifications and endosteal scalloping. Which of the following is the most critical factor in determining the surgical management and prognosis of this primary bone tumor?

Explanation

For conventional chondrosarcoma, histologic grade is the most important prognostic factor and dictates surgical management. High-grade tumors require wide resection, while selected low-grade tumors may be treated with extended intralesional curettage.

Question 57

A 65-year-old man presents with progressive bowing of his tibiae and an increasing hat size. Laboratory tests show markedly elevated serum alkaline phosphatase with normal calcium and phosphorus. A bone biopsy would most likely demonstrate which microscopic finding?

Explanation

Paget's disease of bone is characterized by chaotic and excessive bone remodeling. The hallmark histologic feature is a "mosaic pattern" of irregular cement lines reflecting haphazard episodes of bone resorption and formation.

Question 58

During the incorporation of a cortical structural allograft, the process by which host osteoclasts resorb the graft and osteoblasts lay down new bone in its place is known as:

Explanation

Creeping substitution is the biological process where a dead bone graft is gradually resorbed by host osteoclasts and simultaneously replaced by new bone deposited by host osteoblasts.

Question 59

A 20-year-old man with multiple hereditary exostoses (MHE) notes rapid growth and increasing pain in a previously asymptomatic mass on his distal femur. What is the most reliable MRI finding suggesting malignant transformation to secondary chondrosarcoma?

Explanation

In skeletally mature adults with osteochondromas, a cartilage cap thickness greater than 1.5 to 2 cm on MRI is highly suspicious for malignant transformation to a secondary peripheral chondrosarcoma.

Question 60

According to Perren's strain theory of fracture healing, which type of tissue is capable of tolerating the highest amount of interfragmentary strain before rupturing?

Explanation

Granulation tissue can tolerate up to 100% strain without rupturing, bridging the initial highly mobile fracture gap. As stability increases and strain decreases, the tissue differentiates into cartilage (tolerates ~10% strain) and eventually bone (tolerates ~2% strain).

Question 61

During skeletal muscle contraction, the release of calcium ions from the sarcoplasmic reticulum initiates cross-bridge cycling. Calcium directly binds to which of the following proteins to expose the myosin-binding sites on actin?

Explanation

In skeletal muscle, calcium released from the sarcoplasmic reticulum binds specifically to Troponin C. This interaction induces a conformational change that pulls tropomyosin away, exposing the myosin-binding sites on the actin filament.

Question 62

What factor has the greatest influence on the pullout strength of a cortical screw in diaphyseal bone?

Explanation

The outer diameter of the screw is the most significant factor determining screw pullout strength. This is followed closely by the length of thread engagement in the bone.

Question 63

A 35-year-old man presents with a deep, slow-growing soft tissue mass near his knee joint. Biopsy reveals a biphasic tumor with spindle and epithelial cells. Which of the following chromosomal translocations is most likely associated with this diagnosis?

Explanation

Synovial sarcoma is characterized by the t(X;18) translocation, which results in the SYT-SSX fusion gene. This molecular marker is critical for confirming the diagnosis of synovial sarcoma.

Question 64

In which specific zone of normal articular cartilage are the collagen fibers oriented perpendicular to the joint surface and the chondrocytes arranged in vertical columns?

Explanation

In the deep (radial) zone of articular cartilage, collagen fibers are oriented perpendicularly to the articular surface. Chondrocytes are also arranged in vertical columns to effectively resist compressive forces.

Question 65

When analyzing the stress-strain curve of an orthopedic implant material, the area under the curve strictly within the elastic region represents which mechanical property?

Explanation

Resilience is defined as the area under the stress-strain curve in the elastic region, representing the material's ability to absorb energy without permanent deformation. Toughness is the total area under the entire curve.

Question 66

Which of the following bacterial organisms is most highly associated with early implant-related infections mediated by excessive glycocalyx (biofilm) production?

Explanation

Staphylococcus epidermidis is a coagulase-negative staphylococcus renowned for its ability to produce a robust exopolysaccharide glycocalyx. This biofilm allows it to aggressively adhere to metallic orthopedic implants and evade both host immunity and antibiotics.

Question 67

Denosumab is used in the treatment of postmenopausal osteoporosis and giant cell tumor of bone. What is its precise mechanism of action?

Explanation

Denosumab is a human monoclonal antibody that specifically binds to RANKL. By doing so, it prevents RANKL from interacting with the RANK receptor on osteoclasts, profoundly inhibiting osteoclast formation, function, and survival.

Question 68

Following a peripheral nerve transection, Wallerian degeneration occurs distal to the injury site. Which cells are primarily responsible for clearing myelin debris in the peripheral nervous system to facilitate eventual axonal regeneration?

Explanation

In the peripheral nervous system, Schwann cells and recruited blood-derived macrophages phagocytose myelin and axonal debris during Wallerian degeneration. This clearing process is essential to create a permissible environment for axonal regrowth.

Question 69

Which of the following bone graft options definitively possesses osteoconductive, osteoinductive, and osteogenic properties?

Explanation

Fresh autogenous cancellous bone (e.g., from the iliac crest) remains the gold standard graft. It inherently provides a physical scaffold (osteoconductive), growth factors like BMPs (osteoinductive), and live osteoprogenitor cells (osteogenic).

Question 70

Tranexamic acid (TXA) is widely utilized in major orthopedic procedures to reduce perioperative blood loss. What is the specific molecular mechanism of action of TXA?

Explanation

Tranexamic acid is a synthetic lysine analog and antifibrinolytic agent. It competitively inhibits the activation of plasminogen to plasmin, thereby stabilizing existing fibrin clots and preventing their premature degradation.

Question 71

A 65-year-old man presents with back pain and hypercalcemia. Radiographs demonstrate "punched-out" lytic lesions in the skull and vertebral bodies. Which cytokine is primarily responsible for the aggressive osteoclastic bone resorption seen in this malignant condition?

Explanation

The clinical picture describes multiple myeloma. Myeloma cells and supporting bone marrow stromal cells secrete high levels of IL-6 (and RANKL), which heavily stimulates osteoclastogenesis and leads to characteristic lytic bone lesions.

Question 72

An orthopedic surgeon decides to increase the diameter of a solid titanium intramedullary nail from 10 mm to 12 mm for a femoral shaft fracture. How does this diameter change affect the nail's theoretical bending rigidity?

Explanation

The bending rigidity of a solid cylindrical implant is proportional to the radius to the fourth power (r^4). Increasing the diameter from 10 to 12 mm increases rigidity by (1.2)^4, which equals approximately 2.07.

Question 73

During normal secondary fracture healing, which phase is distinctly characterized by the highest peak of cellular proliferation and the critical transition of soft cartilaginous callus to hard woven bone callus?

Explanation

The reparative phase features intense cellular proliferation, initially forming a soft cartilaginous callus. This soft callus subsequently undergoes endochondral ossification to form a mechanically stable hard bony callus.

Question 74

When comparing different skeletal muscle fiber types, which of the following physiological characteristics is accurately associated with Type I (slow-twitch) fibers compared to Type II (fast-twitch) fibers?

Explanation

Type I fibers are designed for aerobic endurance and sustained postural control. Consequently, they possess high mitochondrial density, rich capillary networks, and high myoglobin content, rendering them highly resistant to fatigue.

Question 75

A 60-year-old man presents with an acutely swollen knee. Aspiration yields cloudy synovial fluid that demonstrates positively birefringent, rhomboid-shaped crystals under compensated polarized light microscopy. What specific material constitutes these crystals?

Explanation

Calcium pyrophosphate dihydrate (CPPD) crystals are the hallmark of pseudogout. They classically appear as rhomboid-shaped crystals with weak positive birefringence under polarized light.

Question 76

Which of the following modern manufacturing modifications to ultra-high-molecular-weight polyethylene (UHMWPE) most significantly decreases its adhesive and abrasive wear rates in total joint arthroplasty?

Explanation

Highly cross-linking UHMWPE with elevated doses of irradiation drastically improves its wear resistance. Subsequent thermal treatment (melting or annealing) is required to extinguish residual free radicals and prevent in vivo oxidative degradation.

Question 77

Which of the following signaling molecules, produced primarily by mature osteocytes, acts as a potent negative regulator of bone formation by inhibiting the Wnt/beta-catenin pathway in osteoblasts?

Explanation

Sclerostin is a glycoprotein selectively secreted by osteocytes that binds to LRP5/6 receptors on osteoblasts. This binding directly inhibits the Wnt/beta-catenin signaling pathway, thereby reducing bone formation.

Question 78

What is widely considered the most significant prognostic factor for overall disease-free survival in a pediatric patient with localized high-grade intramedullary osteosarcoma following neoadjuvant chemotherapy?

Explanation

The histologic response to neoadjuvant chemotherapy is the most powerful prognostic indicator in high-grade osteosarcoma. A good response is typically defined as greater than 90% tumor necrosis in the definitive surgical specimen.

Question 79

Bupivacaine is an amide local anesthetic known for its relatively long duration of action. What is the primary mechanism by which it halts nerve action potential conduction?

Explanation

Local anesthetics enter the nerve cell membrane in their uncharged, lipophilic state and then bind to the intracellular portion of voltage-gated sodium channels. This blockade prevents the sodium influx required for action potential propagation.

Question 80

When applying a dynamic compression plate (DCP) to stabilize a transverse diaphyseal fracture, placing the plate specifically on the tension side of the bone achieves which distinct biomechanical advantage?

Explanation

Applying a plate to the tension side of an eccentrically loaded bone neutralizes distracting tensile forces. It effectively converts the bending moment into stabilizing compressive forces across the far cortex of the fracture.

Question 81

A 30-year-old woman presents with knee pain. Radiographs reveal an eccentric, lytic lesion in the distal femur extending to the subchondral bone. Biopsy shows multinucleated giant cells in a background of mononuclear stromal cells. Which specific cell type in this tumor harbors the neoplastic genetic alteration (e.g., H3F3A mutation)?

Explanation

In Giant Cell Tumor of bone, the true neoplastic cells are the mononuclear spindle-shaped stromal cells, which harbor the signature H3F3A mutation. The abundant multinucleated giant cells are merely reactive, osteoclast-like cells recruited by the stroma.

Question 82

Which of the following modifications to ultra-high-molecular-weight polyethylene (UHMWPE) most effectively reduces adhesive and abrasive wear in total joint arthroplasty?

Explanation

Highly cross-linking UHMWPE significantly improves wear resistance by reducing polymer chain mobility. Subsequent remelting or annealing eliminates free radicals, reducing oxidative degradation.

Question 83

A novel therapeutic agent targets the RANK receptor to inhibit osteoclastogenesis. Which of the following cells primarily expresses the RANK receptor?

Explanation

The RANK receptor is expressed on the surface of osteoclast precursors and mature osteoclasts. Binding of RANKL (produced by osteoblasts) to RANK stimulates osteoclast differentiation and activation.

Question 84

In the treatment of a tibial shaft fracture, reaming the medullary canal and inserting a larger diameter intramedullary nail increases the bending stiffness of the construct. Bending stiffness of a solid cylindrical rod is proportional to the radius raised to which power?

Explanation

The bending stiffness of a solid cylinder is determined by the area moment of inertia, which is proportional to the radius to the fourth power (r^4). Therefore, a small increase in nail diameter significantly increases stiffness.

Question 85

A 45-year-old woman with chronic kidney disease presents with diffuse bone pain. Laboratory studies reveal hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH). What is the primary underlying pathophysiology of her bone disease?

Explanation

Renal osteodystrophy is driven by the failing kidneys' inability to synthesize 1-alpha-hydroxylase, preventing the conversion of 25(OH)D to active 1,25(OH)2D. This leads to hypocalcemia, triggering secondary hyperparathyroidism.

Question 86

A 14-year-old boy presents with a permeative lytic lesion in the diaphysis of his femur.

Biopsy demonstrates small round blue cells. Cytogenetic analysis is most likely to reveal which of the following translocations?

Explanation

The clinical and histologic description is classic for Ewing sarcoma. The most common cytogenetic abnormality in Ewing sarcoma is the t(11;22) translocation, resulting in the EWS-FLI1 fusion protein.

Question 87

Articular cartilage relies on its structural organization for biomechanical competence. Which zone of articular cartilage contains the highest concentration of water and collagen, but the lowest concentration of proteoglycans?

Explanation

The superficial (tangential) zone of articular cartilage has the highest water content and collagen concentration, with collagen fibers oriented parallel to the joint surface to resist shear stress. It has the lowest concentration of proteoglycans.

Question 88

A patient is prescribed rivaroxaban for deep vein thrombosis prophylaxis following a total hip arthroplasty. What is the specific mechanism of action of this medication?

Explanation

Rivaroxaban is a highly selective direct Factor Xa inhibitor. Unlike low-molecular-weight heparins, it does not require antithrombin III to exert its anticoagulant effect.

Question 89

Bone morphogenetic protein-2 (BMP-2) promotes osteoinduction primarily by signaling through which of the following intracellular pathways?

Explanation

BMPs bind to serine/threonine kinase receptors on the cell membrane, which subsequently phosphorylate intracellular Smad proteins (primarily Smad 1, 5, and 8). These translocate to the nucleus to regulate osteogenic gene expression.

Question 90

A 40-year-old man presents with a painless, slow-growing mass in his thigh.

MRI reveals a well-circumscribed lesion that is hyperintense on T1-weighted images and loses signal on fat-suppressed sequences. What is the most likely diagnosis?

Explanation

Lipomas are benign tumors of mature adipose tissue that exhibit high signal intensity on T1-weighted MRI (matching subcutaneous fat) and demonstrate signal drop-out on fat-suppression sequences.

Question 91

Which of the following organisms is a gram-positive, anaerobic rod that is a frequent cause of delayed periprosthetic joint infection in shoulder arthroplasty?

Explanation

Cutibacterium acnes is a gram-positive, slow-growing anaerobic rod naturally found in the sebaceous glands of the shoulder and chest. It is a leading cause of indolent periprosthetic joint infections in shoulder arthroplasty.

Question 92

The pullout strength of a cortical bone screw is most significantly increased by which of the following design alterations?

Explanation

Screw pullout strength is directly proportional to the major diameter and the volume of bone engaged by the threads. Decreasing the thread pitch increases the number of threads per unit length, thereby increasing the bone-thread purchase and pullout strength.

Question 93

During Wallerian degeneration following a peripheral nerve transection, which cells are primarily responsible for clearing myelin debris to allow for axonal regeneration?

Explanation

In the peripheral nervous system, Wallerian degeneration involves the breakdown of the axon and myelin distal to the injury. Schwann cells downregulate myelin production and, alongside recruited macrophages, phagocytose the myelin debris to create a conducive environment for regeneration.

Question 94

A 5-year-old boy presents with multiple fractures, blue sclerae, and hearing loss. This condition is most commonly caused by a mutation affecting which of the following proteins?

Explanation

The clinical presentation is classic for Osteogenesis Imperfecta (OI). OI is predominantly caused by autosomal dominant mutations in the COL1A1 or COL1A2 genes, which lead to qualitative or quantitative defects in Type I collagen.

Question 95

Which structure in the muscle sarcomere contains ONLY thin (actin) filaments and shortens during muscle contraction?

Explanation

The I band contains only actin (thin) filaments and spans across the Z line between two adjacent sarcomeres. During contraction (sliding filament theory), the I band and H zone shorten, while the A band remains the same length.

Question 96

A 35-year-old pregnant woman presents with an expansile, lytic lesion in the distal femur.

Histology reveals multinucleated giant cells distributed uniformly among mononuclear stromal cells. Denosumab therapy is considered. What is the mechanism of action of denosumab in this disease?

Explanation

The diagnosis is Giant Cell Tumor (GCT) of bone. Denosumab is a monoclonal antibody that binds to RANKL, preventing it from interacting with RANK on the multinucleated giant cells, thereby inhibiting their bone-resorbing activity.

Orthopedic Board Review Mock Exam #603: 100 High-Yield MCQs

Orthopedic Basic 2026 MCQs: Board Review Questions & Answers (Part 4)

Key Takeaway

Orthopedic Basic 2026 MCQs: Board Review Questions & Answers (Part 4)

Chapter Index