ABOS Basic Science MCQs: Bone Biology & Biomechanics

Question 1

A 19-year-old girl has had pain and swelling in the right ankle for the past 4 months. She denies any history of trauma. Examination reveals a small soft-tissue mass over the anterior aspect of the ankle and slight pain with range of motion of the ankle joint. The examination is otherwise unremarkable. A radiograph and MRI scan are shown in Figures 45a and 45b, and biopsy specimens are shown in Figures 45c and 45d. What is the most likely diagnosis?

Explanation

Giant cell tumors typically occur in a juxta-articular location involving the epiphysis and metaphysis of long bones, usually eccentric in the bone. The radiographs show a destructive process within the distal tibia and an associated soft-tissue mass. The histology shows multinucleated giant cells in a bland matrix with a few scattered mitoses. Osteosarcoma can have a similar destructive appearance but a very different histologic pattern with osteoid production. Ewing's sarcoma also can have a diffuse destructive process in the bone. The histologic pattern of Ewing's sarcoma is diffuse round blue cells. Aneurysmal bone cysts typically are seen as a fluid-filled lesion on imaging studies and have only a scant amount of giant cells histologically. Metastatic adenocarcinoma does not demonstrate the pattern shown in the patient's histology specimen. Wold LA, et al: Atlas of Orthopaedic Pathology. Philadelphia, PA, WB Saunders, 1990, pp 198-199.

Question 2

A 13-year-old boy has had a painless mass in the arm for the past 2 months. An MRI scan and biopsy specimens are shown in Figures 46a through 46c. What is the most likely diagnosis?

Explanation

Nodular fasciitis is a benign soft-tissue lesion that usually arises from the fascia and is often misdiagnosed as a sarcoma. Desmoid tumors (aggressive fibromatosis) are also benign tumors with a greater tendency for local recurrence. Desmoid tumors have more spindle-shaped fibroblasts in an abundant collagenous matrix. Malignant fibrous histiocytoma is a hypercellular pleomorphic sarcoma more commonly found in adults. The histology is not consistant with a fatty tumor.

Question 3

A 20-year-old man has a symptomatic lesion of fibrous dysplasia in the femoral neck. Management should consist of

Explanation

Fibrous dysplasia in the femoral neck frequently warrants treatment because of the risk of pathologic fracture. Cortical strut grafts reduce the risk of local recurrence compared with cancellous bone grafting. Because of the consequences associated with fracture in this location, prophylactic fixation is recommended. Radiation therapy and chemotherapy are not used for this benign condition. Simon M, et al: Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott Raven, 1998, pp 197.

Question 4

In addition to radiographs of the primary lesion and chest, MRI of the primary lesion, and CT of the chest, staging studies for Ewing's sarcoma should include which of the following?

Explanation

A bone scan and bone marrow biopsy are part of the staging studies for Ewing's sarcoma. Whole body MRI and PET scans are investigational and show promise of greater sensitivity than a bone scan. Schleiermacher G, Peter M, Oberlin O, Philip T, Rubie H, Mechinaud F, et al: Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized ewing tumor. J Clin Oncol 2003;21:85-91.

Question 5

Which of the following conditions is transmitted by an autosomal dominant trait?

Explanation

Multiple hereditary exostosis is transmitted by an autosomal dominant trait. Li-Fraumeni syndrome and retinoblastoma are autosomal recessive or associated with autosomal recessive mutations. No genetic predisposition to Ollier's disease or Maffucci's syndrome has been identified. Mirra J (ed): Bone Tumors: Clinical, Radiologic and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989, p 1627.

Question 6

A previously healthy 13-year-old girl has had thigh pain for the past 3 weeks. The radiograph shown in Figure 47a reveals a lesion in the right femur. A bone scan and CT scan of the chest show no evidence of other lesions. A biopsy specimen is shown in Figure 47b. What is the most likely diagnosis?

Explanation

The patient has Langerhans cell histiocytosis that may be solitary (eosinophilic granuloma) or associated with systemic illness (Hand-Schuller-Christian disease and Letterer-Siwe disease). The solitary form of the disease, eosinophilic granuloma, typically affects patients in the first three decades of life. Radiographically, it is characterized as a well-defined, lytic, "punched out" intramedullary lesion. Histologically, two cell types, eosinophils and Langerhans cells, are seen. The Langerhans cells are seen as mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm. A prominent nuclear groove can be seen in most of the nuclei (coffee bean nuclei). A mixture of inflammatory cells and lipid-laden foam cells with nuclear debris may be present as well. The lack of nuclear atypia and atypical mitoses excludes malignant conditions such as Ewing's sarcoma, lymphoma of bone, and metastatic neuroblastoma. The lack of acute inflammatory cells excludes the diagnosis of osteomyelitis. The eosinophils have bi-lobed nuclei and granular eosinophilic cytoplasm. Dorfman H, Czerniak B: Bone Tumors. St Louis, MO, Mosby, 1988.

Question 7

A 50-year-old man with metastatic renal cell carcinoma has right hip pain. A radiograph and CT scan are shown in Figures 48a and 48b. The first step in management should consist of

Explanation

These lesions are extremely vascular and can cause uncontrolled intraoperative bleeding; therefore embolization is the appropriate first treatment. Because the radiograph and CT scan show a lytic lesion in the supra-acetabular region that affects the weight-bearing dome and medial wall, the next step in treatment would most likely be a total hip arthroplasty and acetabular reconstruction. Treatment with bisphosphonates and radiation therapy will not prevent an acetabular fracture. Cementoplasty is an emerging technique in which cement is injected percutaneously into a lesion, but no long-term results have been reported. Radiofrequency ablation of bone metastases is also an emerging technique that provides palliative pain control. Layalle I, Flandroy P, Trotteur G, Dondelinger RF: Arterial embolization of bone metastases: Is it worthwhile? J Belge Radiol 1998;81:223-225.

Question 8

What is the most common benign bone tumor in childhood?

Explanation

The most common benign bone tumor in childhood is a nonossifying fibroma. It is estimated that 30% of children have a nonossifying fibroma. In most patients, the lesion is not identified until a radiograph is obtained for unrelated reasons. Similarly, most identified cases of fibrous cortical defect are not biopsied because the radiographic and clinical presentations are diagnostic. Aboulafia AJ, Kennon RE, Jelinek JS: Benign bone tumors of childhood. J Am Acad Orthop Surg 1999;7:377-388.

Question 9

A 13-year-old patient has foot drop and lateral knee pain. AP and lateral radiographs and an MRI scan are shown in Figures 49a through 49c. A biopsy specimen is shown in Figure 49d. What is the preferred method of treatment?

Explanation

The "sunburst" radiographic appearance suggests an osteosarcoma, and the histologic findings confirm the diagnosis with malignant cells surrounded by pink osteoid. MRI scans are not particularly helpful in the diagnosis of osteosarcoma but are mandatory for surgical planning. Osteosarcomas are high-grade sarcomas that are best treated with chemotherapy and wide resection. Even though the peroneal nerve is involved, limb salvage is indicated. Survival after limb salvage is equivalent to amputation, with better function. Goorin AM, Abelson HT, Frei E: Osteosarcoma: Fifteen years later. N Engl J Med 1985;313:1637. Link MP, Goorin AM, Miser AW, et al: The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986;314:1600.

Question 10

A 13-year-old girl is diagnosed with a stage IIB osteosarcoma of the proximal tibia. Following neoadjuvant chemotherapy, local control should consist of

Explanation

Local control of osteosarcoma consists of wide resection and reconstruction. Radiation therapy is not recommended except in unresectable lesions or for palliation. Curettage and bone grafting result in intralesional resection with an unacceptable high rate of local recurrence. Chemotherapy alone is not adequate for local control. Simon M, Springfield D, et al: Osteogenic Sarcoma: Surgery for Bone and Soft Tissue. Philadelphia, PA, Lippincott Raven, 1998, p 274.

Question 11

A 23-year-old woman has had vague left knee pain for the past 6 months. A radiograph and CT scan are shown in Figures 50a and 50b. What is the most likely diagnosis?

Explanation

The radiographic appearance of the lesion emanating from the posterior cortex of the left distal femur is consistent with a surface bone-producing lesion; therefore, the most likely diagnosis is a parosteal osteosarcoma. In an osteochondroma, the cortex and medullary cavity of the lesion are in continuity with that of the native bone. A dedifferentiated chondrosarcoma has histologic components of a high-grade sarcoma plus a benign or low-grade malignant cartilage tumor. Tumoral calcinosis is characterized by amorphous calcium in the soft tissues and does not emanate from the bone itself. While often confused with parosteal osteosarcoma, myositis ossificans is usually more mature at the periphery of the lesion rather than the center. In addition, myositis ossificans does not involve the underlying cortex but remains separate from the bone. Unni KK: Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, ed 5. Philadelphia, PA, Lippincott-Raven, 1996, pp 185-196.

Question 12

What is the preferred treatment of a patient with breast cancer and a pathologic fracture of the clavicle in her dominant arm?

Explanation

Closed management should be attempted for upper extremity pathologic fractures, particularly the clavicle. If nonunion or pain persists, surgery may be indicated. Radiofrequency ablation is not indicated for subcutaneous bones. Early motion is likely to cause increased pain and disability. Weber KC, Lewis VO, Randall RL, Lee AK, Springfield D: An approach to the management of the patient with metastatic bone disease. Instr Course Lect 2004;53:663-676.

Question 13

A 14-year-old boy has an asymptomatic mass on the right arm. MRI scans and biopsy specimens are shown in Figures 51a through 51d. Immunostaining is positive for desmin. Additional staging studies should include

Explanation

The patient has rhabdomyosarcoma. Axilliary node and bone marrow biopsy are part of the staging because about 12% of patients with rhabdomyosarcoma of the extremity have evidence of lymph nodes metastases at presentation. Bone marrow metastases have been shown to portend a worse prognosis. Lawrence W, Jr., Hays DM, Heyn R, Tefft M, Crist W, Beltangady M, et al: Lymphatic metastases with childhood rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study. Cancer 1987;60:910-915.

Question 14

A 15-year-old girl has left knee pain and an enlarging mass in the distal thigh. AP and lateral radiographs are shown in Figures 52a and 52b, and a biopsy specimen is shown in Figure 52c. What is the most likely diagnosis?

Explanation

A bone-producing lesion in the metaphysis of an adolescent is most likely an osteosarcoma. The radiographs show a distal femoral bone-producing lesion extending into the surrounding soft tissues. The histologic appearance consists of pleomorphic cells producing osteoid. Ewing's sarcoma and metastatic neuroblastoma do not produce a matrix. Chondrosarcoma is a radiographically destructive lesion with calcification and cartilage cells on histologic section. An osteochondroma is a benign cartilage lesion that is continuous with the medullary cavity of the underlying bone and extends into a bony lesion and covered by a cartilage cap. Unni KK: Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, ed 5. Philadelphia, PA, Lippincott-Raven, 1996, pp 143-160.

Question 15

Survival rates for children with soft-tissue sarcoma other than rhabdomyosarcoma are best correlated with

Explanation

In review of 154 patients with nonrhabdomyosarcoma, Rao reported that histologic grade, tumor invasiveness, and adequate surgical margin were the most important prognostic factors. Histologic subtype, use of adjuvant chemotherapy, and patient age were not as important. Size related to degree of invasiveness was not statistically significant. Rao BN: Nonrhabdomyosarcoma in children: Prognostic factors influencing survival. Semin Surg Oncol 1993;9:524-531. Andrassy R, et al: Non-rhabdomyosarcoma Soft-Tissue Sarcomas: Pediatric Surgical Oncology. Philadelphia, PA, WB Saunders, p 221.

Question 16

A 25-year-old woman has had pain and stiffness in her knee following a motor vehicle accident 9 months ago. The radiograph, CT scan, MRI scan, and biopsy specimen are shown in Figures 53a through 53d. What is the most likely diagnosis?

Explanation

Heterotopic ossification may occur spontaneously or following trauma. The imaging studies and histology reveal mature fatty bone marrow and trabecular bone. Osteochondromas are cortically based with the medullary canal extending into the lesion. This is not evident in this patient. Also, no obvious cartilage cap is present. Parosteal osteosarcoma commonly occurs in the posterior distal femoral cortex but is ruled out by the lack of the typical fibrous stromal cells forming the low-grade malignant osteoid. The histology and clinical presentation eliminate osteomyelitis and osteoblastoma. Horne LT, Blue BA: Intra-articular heterotopic ossification in the knee following intramedullary nailing of the fractured femur using a retrograde method. J Orthop Trauma 1999;13:385-388. Stannard JP, Wilson TC, Sheils TM, McGwin G Jr, Volgas DA, Alonso JE: Heterotopic ossification associated with knee dislocation. Arthroscopy 2002;18:835-839.

Question 17

Which of the following lesions most closely resembles Ewing's sarcoma histologically?

Explanation

Ewing's sarcoma is characterized by small round blue cells. Lesions with a similar appearance include lymphoma, primitive neuroectodermal tumor, rhabdomyosarcoma, small cell lung tumor, and metastatic neuroblastoma. Karyotyping, immunohistochemistry, and electron microscopy can help differentiate these lesions.

Question 18

Primary chondrosarcoma of bone most commonly occurs in which of the following locations?

Explanation

The most common location of chondrosarcoma is the pelvis (30%), followed by the proximal femur (20%) and shoulder girdle (15%). Chondrosarcoma rarely affects the spine or hand. Lee FY, Mankin HJ, Fondren G, et al: Chondrosarcoma of bone: An assessment of outcome. J Bone Joint Surg Am 1999;81:326-338.

Question 19

An 18-year-old man has had an enlarging mass in his hand for the past 3 months. Radiographs, an MRI scan, and biopsy specimens are shown in Figures 54a through 54d. What is the most likely diagnosis?

Explanation

Also known as Nora's lesion, BPOP is a benign osteocartilaginous tumor that almost always occurs in the hands and feet; one occurrence each in the femur and tibia has been reported. Although local recurrence is common after excision, metastases have not been reported. Abramovici L, Steiner GC: Bizarre parosteal osteochondromatous proliferation (Nora's lesion): A retrospective study of 12 cases, 2 arising in long bones. Hum Pathol 2002;33:1205-1210.

Question 20

A 55-year-old man has had a mass in his right thigh for the past 2 months. An MRI scan and biopsy specimens are shown in Figures 55a through 55c. What is the most likely diagnosis?

Explanation

The histology shows extraskeletal myxoid chondrosarcoma, characterized by abundant blue myxoid matrix with cords and nests of small tumor cells. Treatment consists of wide resection. Despite the name, hyaline cartilage is not a common component of these tumors. Adult rhabdomyosarcoma and malignant fibrous histiocytoma are highly pleomorphic sarcomas often containing multinucleated giant cells. Myxoid liposarcoma contains a prominent capillary network and lipoblasts. Myxoma is less cellular than extraskeletal myxoid chondrosarcoma and does not have a cord-like arrangement of tumor cells.

Question 21

Figures 56a through 56c show the radiograph, CT scan, and biopsy specimen of a 44-year-old man who underwent chemotherapy and radiation therapy for lymphoma of the distal femur 20 years ago. His current problem is most likely related to

Explanation

The patient has changes consistent with radiation therapy to the femur, including osteopenia and an aggressive appearing neoplasm. The tumor is most likely a radiation-induced sarcoma. This is more likely than recurrent lymphoma at this late date. It is not related to steroid use or a primary lung tumor. Mirra J (ed): Bone Tumors: Clinical, Radiologic and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989, p 353.

Question 22

What is the most common reason an individual with a malignant soft-tissue tumor in the extremities seeks medical attention?

Explanation

Unlike malignant bone tumors, malignant soft-tissue tumors usually are asymptomatic and present with the presence of a mass. Malignant soft-tissue tumors enlarge by centrifugal growth, creating a mass while compressing surrounding tissue. Symptoms may develop as the result of direct compression on neurovascular structures as the tumor enlarges. This is especially true in the pelvis where the tumor can enlarge appreciably without being noticed. However, in the extremities, the tumor is most often apparent before neurologic symptoms develop. An asymptomatic mass is not necessarily benign; therefore, biopsy should not be delayed. It is uncommon for a malignant soft-tissue mass to be discovered incidentally. Soft-tissue tumors are not typically apparent on radiographs; they are best identified with MRI. Brouns F, Stas M, De Wever I: Delay in diagnosis of soft tissue sarcomas. Eur J Surg Oncol 2003;29:440-445. Rougraff B: The diagnosis and management of soft tissue sarcomas of the extremities in the adult. Curr Probl Cancer 1999;23:1-50.

Question 23

Exostoses in which of the following anatomic locations is the most likely to undergo malignant transformation in a patient with multiple hereditary exostosis (MHE)?

Explanation

Although osteochondromas can occur in almost every bone in patients with MHE, proximally located lesions are more likely to undergo malignant transformation. Annual radiographs of the shoulder girdles and pelvis are indicated in patients with MHE. Any enlarging osteochondromas are a concern as possible malignancies. Peterson HA: Multiple hereditary osteochondromata. Clin Orthop 1989;239:222.

Question 24

Initial management of a pathologic fracture of the humerus secondary to a unicameral bone cyst should include

Explanation

Most pathologic humeral fractures secondary to a unicameral bone cyst are minimally displaced and should be immobilized and allowed to heal. Persistent and/or progressive lesions may require treatment. Various treatments of unicameral bone cysts have been described. Acceptable treatment options include curettage and bone grafting, intralesional steroid injection, and percutaneous grafting with bone graft substitutes. MRI is not indicated when the diagnosis of unicameral bone cyst is known. Wilkins RM: Unicameral bone cysts. J Am Acad Orthop Surg 2000;8:217-224.

Question 25

An 11-year-old child has Ewing's sarcoma of the femoral diaphysis with a small soft-tissue mass. Staging studies show no evidence of metastases. Treatment should consist of

Explanation

The use of chemotherapy has dramatically improved survival rates of patients with Ewing's sarcoma. Local disease is best handled with wide resection to decrease local recurrence and to avoid the complications of radiation therapy (ie, secondary sarcomas). Radiation therapy alone is reserved for unresectable lesions or poor surgical margins. Amputation generally is not necessary. Toni A, Neff JR, Sudanese A, et al: The role of surgical therapy in patients with non-metastatic Ewing's sarcoma of the limbs. Clin Orthop 1991;286:225. Picci P, Rougraff BT, Bacci G, et al: Prognostic significance of histopathologic response to chemotherapy in non-metastatic Ewing's sarcoma of the extremities. J Clin Oncol 1993;11:1763.

Question 26

Sclerostin is a key regulatory glycoprotein secreted by osteocytes to inhibit bone formation. Its mechanism of action involves directly antagonizing which of the following intracellular signaling pathways?

Explanation

Sclerostin inhibits bone formation by binding to LRP5/6 receptors on osteoblasts. This action competitively blocks Wnt from binding, thereby inhibiting the Wnt/beta-catenin signaling pathway necessary for osteoblastogenesis.

Question 27

A trauma surgeon is comparing different implant materials for a diaphyseal fracture fixation. Which of the following lists correctly orders materials by decreasing Young's modulus (stiffness)?

Explanation

Young's modulus measures the stiffness of a material. The correct order from most stiff to least stiff is Cobalt-Chromium (220 GPa) > Stainless Steel (200 GPa) > Titanium (110 GPa) > Cortical bone (15-20 GPa).

Question 28

According to Perren's strain theory of fracture healing, which of the following tissues can tolerate the highest level of interfragmentary strain before mechanical failure?

Explanation

Perren's strain theory dictates that tissues form based on the strain environment. Granulation tissue tolerates up to 100% strain, whereas cartilage tolerates up to 10%, and lamellar bone only tolerates <2% strain.

Question 29

An infant presents with diffuse osteosclerosis and recurrent fractures. Genetic testing reveals a mutation in the CLCN7 gene. This condition primarily affects which of the following cellular mechanisms?

Explanation

Mutations in CLCN7 (a chloride channel) or Carbonic Anhydrase II cause osteopetrosis. These mutations prevent the osteoclast from properly acidifying Howship's lacuna, rendering them unable to resorb bone effectively.

Question 30

During wear of an ultra-high-molecular-weight polyethylene (UHMWPE) component in total joint arthroplasty, submicron particles are generated. Which cell type is primarily responsible for phagocytosing these particles and initiating the osteolytic cascade?

Explanation

Macrophages are the primary cells that phagocytose submicron UHMWPE wear particles. Upon activation, they release pro-inflammatory cytokines like TNF-alpha and IL-1, which stimulate osteoclast-mediated bone resorption.

Question 31

Bone morphogenetic protein 2 (BMP-2) stimulates osteoblast differentiation. Upon binding to its serine/threonine kinase receptor, which intracellular signaling molecules are directly phosphorylated to translocate to the nucleus?

Explanation

BMPs signal via cell-surface serine/threonine kinase receptors. Activation of these receptors leads to the phosphorylation of receptor-regulated Smads (Smad 1, 5, and 8), which then complex with Smad 4 to enter the nucleus and regulate gene transcription.

Question 32

Fibroblast growth factor 23 (FGF-23) plays a critical role in mineral homeostasis. Which of the following accurately describes its primary cellular source and its main renal effect?

Explanation

FGF-23 is primarily secreted by osteocytes in response to high phosphate levels. It acts on the kidneys to decrease phosphate reabsorption (causing phosphaturia) and downregulates 1-alpha-hydroxylase.

Question 33

On a load-deformation (stress-strain) curve of a bone specimen, the total area under the entire curve before the point of failure represents which specific mechanical property?

Explanation

The area under the entire stress-strain curve represents toughness, which is the total amount of energy a material can absorb before it fractures. Stiffness is the slope of the linear elastic region.

Question 34

Denosumab is highly effective in the management of osteoporosis and giant cell tumors of bone. It exerts its therapeutic effect by mimicking the physiological function of which endogenous molecule?

Explanation

Denosumab is a fully human monoclonal antibody that binds to and neutralizes RANKL. This mechanism mimics the action of the endogenous decoy receptor Osteoprotegerin (OPG), effectively inhibiting osteoclast activation.

Question 35

A 3-year-old child presents with short stature, rhizomelic shortening of the limbs, and frontal bossing. This condition is typically caused by a gain-of-function mutation in FGFR3. Which zone of the physis is primarily affected?

Explanation

Achondroplasia is caused by an activating mutation in the FGFR3 gene. This overactivity profoundly suppresses chondrocyte division in the proliferative zone of the physis, leading to stunted endochondral ossification.

Question 36

A polymeric orthopedic implant subjected to a constant physiological load over a prolonged period exhibits progressive, slow deformation. This viscoelastic behavior is known as:

Explanation

Creep is the slow, progressive deformation of a material under a constant load over time. Stress relaxation, conversely, is the decrease in stress over time when a material is held at a constant deformation.

Question 37

Osteogenesis imperfecta is most commonly caused by mutations in the COL1A1 or COL1A2 genes. These mutations typically result in the substitution of which critical amino acid, disrupting the collagen triple helix?

Explanation

Type I collagen has a repeating Glycine-X-Y sequence. Mutations in osteogenesis imperfecta typically cause bulky amino acids to substitute for glycine, which normally fits into the tight center of the collagen triple helix.

Question 38

Regarding the normal ultrastructure of articular cartilage, which zone contains the highest concentration of water and features collagen fibers oriented parallel to the joint surface?

Explanation

The superficial (tangential) zone of articular cartilage has the highest water and highest collagen content. Its collagen fibers are aligned parallel to the articular surface to resist shear stresses.

Question 39

A surgeon mistakenly utilizes titanium alloy screws to secure a stainless steel dynamic compression plate. This combination of dissimilar metals in an electrolytic fluid environment primarily predisposes the construct to which type of corrosion?

Explanation

Galvanic corrosion occurs when two electrochemically dissimilar metals are in direct contact within an electrolytic environment (like body fluid). The less noble metal undergoes accelerated anodic corrosion.

Question 40

Cleidocranial dysplasia is characterized by hypoplastic clavicles, delayed cranial suture closure, and supernumerary teeth. It is caused by a genetic mutation in the master transcription factor for osteoblast differentiation. Which gene is affected?

Explanation

RUNX2 (also known as CBFA1) is the master transcription factor required for the differentiation of mesenchymal stem cells into osteoblasts. Loss-of-function mutations in RUNX2 cause cleidocranial dysplasia.

Question 41

Primary bone healing occurs under conditions of absolute stability without radiographically visible callus formation. Which of the following is the key microscopic mechanism driving this process?

Explanation

Primary bone healing relies on Haversian remodeling via cutting cones. Osteoclasts bore across the fracture line, immediately followed by osteoblasts laying down lamellar bone, requiring less than 2% interfragmentary strain.

Question 42

Parathyroid hormone (PTH) regulates serum calcium homeostasis. Which of the following accurately describes the effect of intermittent, low-dose exogenous administration of PTH (e.g., teriparatide)?

Explanation

While continuous PTH leads to net bone resorption, intermittent low-dose PTH (teriparatide) exerts an anabolic effect. It disproportionately stimulates osteoblastic bone formation over osteoclastic resorption and inhibits osteoblast apoptosis.

Question 43

A researcher is evaluating markers of bone turnover in patient serum. Which of the following markers is considered the most specific indicator of mature osteoblast activity and bone formation?

Explanation

Osteocalcin is the most abundant non-collagenous protein in bone matrix and is highly specific to mature osteoblasts. TRAP and Cathepsin K are markers of osteoclast activity, whereas Type X collagen marks hypertrophic chondrocytes.

Question 44

Type IV delayed hypersensitivity reactions have been implicated in some cases of unexplained pain and aseptic loosening in total joint arthroplasty. This immunological reaction is primarily mediated by which cells?

Explanation

Metal allergy in joint replacement is a Type IV delayed hypersensitivity reaction. It is a cell-mediated response driven primarily by sensitized T-lymphocytes upon re-exposure to the antigen.

Question 45

A pediatric patient with X-linked hypophosphatemic rickets presents with progressive lower extremity bowing. Pathophysiologically, this condition is driven by a mutation in the PHEX gene, leading to the overactivity of which regulatory hormone?

Explanation

X-linked hypophosphatemia is caused by a PHEX gene mutation that fails to downregulate FGF-23. The resulting excess of FGF-23 causes massive renal phosphate wasting and impairs bone mineralization.

Question 46

A 65-year-old woman is prescribed a medication for osteoporosis that works by binding to and inhibiting RANKL. What is the primary cellular effect of this medication?

Explanation

Denosumab is a monoclonal antibody that binds to RANKL, preventing its interaction with RANK on osteoclasts. This inhibits osteoclast maturation, function, and survival, leading to decreased bone resorption.

Question 47

A 50-year-old woman undergoes total hip arthroplasty with a highly cross-linked polyethylene liner. Which of the following best describes the mechanical consequence of high cross-linking compared to conventional polyethylene?

Explanation

Highly cross-linked polyethylene significantly increases wear resistance by restricting polymer chain mobility. However, this alteration mechanically leads to decreased fatigue resistance, yield strength, and ductility.

Question 48

A 40-year-old man sustains a transverse femoral shaft fracture treated with a rigid locked intramedullary nail. Which type of bone healing will predominate at the fracture site?

Explanation

Intramedullary nailing provides relative stability, which permits micromotion at the fracture site. This mechanical environment promotes secondary bone healing via callus formation, which occurs predominantly through endochondral ossification.

Question 49

Which of the following signaling pathways is directly stimulated by the binding of bone morphogenetic protein-2 (BMP-2) to its cell surface receptor on mesenchymal stem cells?

Explanation

BMP-2 binds to serine/threonine kinase receptors and primarily transduces signals through the intracellular Smad 1/5/8 pathway. In contrast, TGF-beta primarily utilizes the Smad 2/3 signaling cascade.

Question 50

A 4-year-old boy presents with short stature, frontal bossing, and bowing of the lower extremities. Laboratory tests show normal serum calcium, decreased serum phosphate, and elevated alkaline phosphatase. Genetic testing reveals a mutation in the PHEX gene. What is the primary mechanism responsible for his condition?

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX gene mutation, leading to the overproduction of FGF-23. Excess FGF-23 inhibits renal reabsorption of phosphate and decreases 1-alpha-hydroxylase activity, resulting in hypophosphatemia.

Question 51

A 60-year-old man is treated with a medication that stimulates bone formation by inhibiting sclerostin. Which signaling pathway is directly upregulated by this medication?

Explanation

Romosozumab is a monoclonal antibody against sclerostin. Sclerostin is a natural inhibitor of the Wnt/beta-catenin pathway; thus, its inhibition upregulates Wnt signaling and increases osteoblast activity.

Question 52

In the context of bone biomechanics, which of the following terms best describes a material's continuous increase in strain over time when subjected to a constant load?

Explanation

Creep is the progressive deformation (strain) of a viscoelastic material under a constant applied load. Stress relaxation, conversely, is the decrease in stress over time under a constant strain.

Question 53

A researcher is evaluating the use of continuous versus intermittent parathyroid hormone (PTH) therapy on bone mass. Which of the following best describes the effect of intermittent PTH administration?

Explanation

Intermittent administration of PTH has an osteoanabolic effect, stimulating osteoblast-mediated bone formation more than osteoclast-mediated bone resorption. This is the mechanism of action for teriparatide.

Question 54

A 2-year-old child presents with frequent fractures and bluish sclerae. A mutation in the COL1A1 gene is identified. Which of the following structural defects in collagen is most likely present?

Explanation

Osteogenesis imperfecta is most commonly caused by a genetic mutation leading to the substitution of glycine with a bulkier amino acid in the type I collagen triple helix. This prevents proper triple-helical folding and structural integrity.

Question 55

What is the primary mechanism of action of nitrogen-containing bisphosphonates (e.g., alendronate) in the treatment of osteoporosis?

Explanation

Nitrogen-containing bisphosphonates inhibit farnesyl pyrophosphate synthase within the mevalonate pathway. This disruption prevents the prenylation of small GTPase proteins, leading to osteoclast apoptosis.

Question 56

A 35-year-old man requires a posterolateral lumbar fusion. He is a chronic smoker. Which phase of bone graft incorporation is most likely impaired by the direct effects of nicotine?

Explanation

Nicotine is a potent vasoconstrictor and inhibits angiogenesis, significantly impairing the neovascularization phase of bone graft incorporation. This leads to higher rates of nonunion in smokers.

Question 57

During the evaluation of a new titanium alloy for use in intramedullary nails, researchers find that it has a lower modulus of elasticity than stainless steel. What is the primary clinical advantage of this property?

Explanation

A lower modulus of elasticity indicates greater flexibility, making the material's stiffness closer to that of cortical bone. This reduces stress shielding, which can prevent secondary osteopenia of the adjacent bone.

Question 58

A 45-year-old woman presents with symmetrical polyarthritis of the hands and wrists. Radiographs show periarticular osteopenia and marginal erosions. Which cytokine is the primary driver of osteoclast activation and subsequent bone erosion in this condition?

Explanation

In rheumatoid arthritis, TNF-alpha and IL-1 are the key pro-inflammatory cytokines that stimulate the RANK/RANKL pathway. This overactivation drives osteoclastogenesis and the formation of characteristic marginal erosions.

Question 59

An 8-year-old boy presents with failure to thrive and recurrent fractures. Radiographs reveal diffuse osteosclerosis and loss of the medullary canal. A defect in which of the following is most likely responsible for his condition?

Explanation

Osteopetrosis is characterized by dense but brittle bones due to defective osteoclast function. It is often caused by a mutation in carbonic anhydrase II or TCIRG1, preventing osteoclasts from acidifying the resorption pit.

Question 60

A patient sustains a displaced midshaft clavicle fracture. Which type of ossification primarily formed this bone during embryogenesis?

Explanation

The clavicle is unique as the first bone to ossify in the embryo and does so via both intramembranous (medial and central portions) and endochondral (medial and lateral extremes) ossification.

Question 61

Fresh frozen allograft is commonly used in orthopedic reconstructive procedures. Which of the following properties is preserved in a fresh frozen allograft compared to an autograft?

Explanation

Fresh frozen allografts are osteoinductive (retaining proteins like BMPs) and osteoconductive (providing a structural scaffold). However, they lack living cells and are therefore not osteogenic.

Question 62

A 25-year-old man with Marfan syndrome requires surgery for a severe scoliosis. His condition is caused by a mutation in the fibrillin-1 gene. This mutation leads to dysregulation of which of the following signaling molecules?

Explanation

Fibrillin-1 normally binds to and sequesters TGF-beta in the extracellular matrix. A mutation in fibrillin-1 leads to excess bioavailable TGF-beta, which drives the connective tissue abnormalities seen in Marfan syndrome.

Question 63

The process of aseptic loosening in total joint arthroplasty is largely driven by particulate wear debris. Which of the following cell types is primarily responsible for phagocytosing this debris and releasing pro-inflammatory cytokines?

Explanation

Macrophages recognize and phagocytose particulate wear debris, such as ultra-high-molecular-weight polyethylene. In response, they release cytokines (TNF-alpha, IL-1, IL-6) that recruit and activate osteoclasts, leading to osteolysis.

Question 64

Which of the following represents the primary difference in mechanical properties between cortical bone and cancellous bone?

Explanation

Cortical bone is significantly stiffer (higher elastic modulus) and less ductile than cancellous bone. Cancellous bone is highly porous and can undergo considerable strain before failing.

Question 65

The transcription factor Runx2 (Cbfa1) is essential for the differentiation of which cell type?

Explanation

Runx2 (also known as Cbfa1) is the master transcription factor required for the commitment of mesenchymal stem cells to the osteoblast lineage. Heterozygous mutations in RUNX2 cause cleidocranial dysplasia.

Question 66

Which of the following bone graft substitutes possesses both osteoconductive and osteoinductive properties, but lacks osteogenic potential?

Explanation

DBM contains bone morphogenetic proteins (BMPs) providing osteoinduction, and collagen matrix for osteoconduction. It undergoes processing that removes viable cells, thus lacking osteogenic potential.

Question 67

In the biomechanical design of orthopedic screws, which of the following modifications most significantly increases the pullout strength in cancellous bone?

Explanation

Screw pullout strength is most directly proportional to the major (outer) diameter of the thread. Increasing the major diameter provides the greatest increase in pullout resistance.

Question 68

Which zone of articular cartilage is characterized by chondrocytes aligned parallel to the joint surface, the highest water content, and the lowest proteoglycan concentration?

Explanation

The superficial zone has collagen fibers and chondrocytes oriented parallel to the joint surface to resist shear forces. It contains the highest proportion of water and the lowest concentration of proteoglycans.

Question 69

A 55-year-old patient with end-stage renal disease presents with diffuse bone pain. Laboratory evaluation reveals hypocalcemia, hyperphosphatemia, and significantly elevated parathyroid hormone (PTH) levels. The underlying pathogenesis of this patient's metabolic bone disease is primarily initiated by a deficiency of which enzyme?

Explanation

Patients with chronic kidney disease lack 1-alpha-hydroxylase activity, leading to decreased active Vitamin D (1,25-dihydroxycholecalciferol). This causes decreased calcium absorption, triggering secondary hyperparathyroidism.

Question 70

During bone resorption, osteoclasts attach to the underlying bone matrix via a specific cell surface receptor that binds to osteopontin and bone sialoprotein. Which of the following is the primary receptor involved in this sealing zone formation?

Explanation

Osteoclasts utilize the Alpha-v beta-3 integrin to bind the RGD (arginine-glycine-aspartic acid) sequences found in bone matrix proteins like osteopontin, creating the actin ring and sealing zone necessary for resorption.

Question 71

When comparing titanium alloy (Ti-6Al-4V) to 316L stainless steel for fracture fixation plates, which of the following statements is true regarding titanium?

Explanation

Titanium alloy has a lower modulus of elasticity (closer to that of cortical bone) compared to stainless steel, which decreases stress shielding. It is highly notch sensitive and uses a titanium dioxide passivation layer.

Question 72

To decrease the stiffness of a locking plate construct and promote secondary bone healing via callus formation in a comminuted diaphyseal fracture, which technique should the surgeon employ?

Explanation

Increasing the working length of the plate (the distance between the innermost screws on either side of the fracture) decreases the overall construct stiffness, allowing interfragmentary motion that stimulates secondary bone healing.

Question 73

During an anterior cruciate ligament reconstruction, the graft is tensioned to 80 Newtons and secured at a fixed length. Over the next several minutes, the tension within the graft progressively decreases. Which viscoelastic property does this describe?

Explanation

Stress relaxation is the decrease in stress (or tension) over time when a viscoelastic material is held at a constant strain (constant length). Creep is the increase in strain over time under a constant load.

Question 74

What is the primary mode of wear in a well-functioning standard ultra-high molecular weight polyethylene (UHMWPE) on metal articulation in total hip arthroplasty?

Explanation

Adhesive wear is the predominant wear mechanism in typical metal-on-polyethylene articulations, occurring when microscopic asperities on the bearing surfaces adhere to each other and break off.

Question 75

During distraction osteogenesis (e.g., Ilizarov technique), the newly formed bone in the distraction gap regenerates primarily via which biological process?

Explanation

Distraction osteogenesis occurs primarily through intramembranous ossification, where mesenchymal stem cells differentiate directly into osteoblasts to form bone under mechanical tension, without a cartilaginous intermediate.

Question 76

Which of the following characteristics accurately describes Type I (slow-twitch) skeletal muscle fibers?

Explanation

Type I (slow-twitch) fibers are fatigue-resistant, rely on oxidative (aerobic) metabolism, and have high concentrations of mitochondria and myoglobin, which facilitates sustained endurance activities.

Question 77

Teriparatide is used in the treatment of severe osteoporosis. Its anabolic effect on bone is primarily achieved through which of the following mechanisms?

Explanation

Teriparatide is a recombinant PTH analog. When given intermittently (e.g., daily injections), it exerts an anabolic effect by stimulating osteoblast proliferation and inhibiting osteoblast apoptosis, leading to net bone formation.

Question 78

Which of the following is the most abundant non-collagenous protein in the bone extracellular matrix and serves as a marker for mature osteoblast activity?

Explanation

Osteocalcin is the most abundant non-collagenous protein in bone. Produced by mature osteoblasts, it contains vitamin K-dependent gamma-carboxyglutamic acid residues that bind calcium and regulate mineralization.

Question 79

A genetic mutation in the gene encoding carbonic anhydrase II results in the inability of osteoclasts to acidify the resorption pit. This defect is the primary pathogenesis of which condition?

Explanation

Osteopetrosis is caused by impaired osteoclast function. Mutations in carbonic anhydrase II or the TCIRG1 vacuolar proton pump prevent the acidification of Howship's lacuna, halting bone resorption and leading to overly dense, brittle bone.

Question 80

A 4-year-old child presents with bleeding gums, petechiae, and metaphyseal radiolucent bands on radiographs (Frankel's line). The underlying nutritional deficiency impairs collagen synthesis by directly affecting which enzymatic process?

Explanation

Scurvy is caused by Vitamin C deficiency. Vitamin C is a required cofactor for prolyl hydroxylase and lysyl hydroxylase, which hydroxylate proline and lysine residues essential for the stable triple helix structure of collagen.

Question 81

If a surgeon chooses to upsize a solid intramedullary nail by doubling its radius, the torsional rigidity of the new nail increases by a factor of what?

Explanation

The torsional rigidity of a solid cylinder is proportional to its polar moment of inertia, which scales with the radius to the fourth power (r^4). Therefore, doubling the radius increases torsional rigidity by a factor of 16.

Question 82

The high compressive strength and stiffness of articular cartilage are primarily provided by the interaction between interstitial water and which macromolecule?

Explanation

Aggrecan, the major proteoglycan in articular cartilage, contains highly negatively charged glycosaminoglycans (chondroitin and keratin sulfate). This creates a Donnan osmotic swelling pressure that traps water, providing compressive stiffness.

Question 83

Fibroblast growth factor 23 (FGF-23) plays a critical role in mineral metabolism. Which of the following describes its primary physiological effect?

Explanation

FGF-23 is secreted by osteocytes in response to high serum phosphate. It acts on the kidneys to increase phosphate excretion (by downregulating Na/Pi cotransporters) and reduces active vitamin D synthesis by inhibiting 1-alpha-hydroxylase.

Question 84

During the early phases of fracture healing, mesenchymal stem cells differentiate into chondrocytes to form a soft callus. Which transcription factor is essential for committing these cells to the chondrogenic lineage?

Explanation

Sox9 is the master transcription factor required for chondrocytic differentiation. Runx2 and Osterix are critical for osteoblastic differentiation, while NFATc1 regulates osteoclastogenesis.

Question 85

Which of the following forms of implant corrosion occurs specifically due to microscopic cyclic motion between two closely fitted metal surfaces, leading to disruption of the passive oxide layer?

Explanation

Fretting corrosion is caused by micromotion between two mating components (e.g., screw head and plate hole, or modular hip tapers). The friction mechanically disrupts the protective oxide layer, accelerating local corrosive wear.

Question 86

A 68-year-old postmenopausal woman with severe osteoporosis is started on denosumab therapy. What is the precise mechanism of action of this pharmacological agent?

Explanation

Denosumab is a monoclonal antibody that targets and binds to RANKL, preventing it from interacting with the RANK receptor on osteoclasts. This mimics the action of osteoprotegerin (OPG), thereby profoundly inhibiting osteoclast maturation, function, and survival.

Question 87

A patient undergoes a total hip arthroplasty utilizing a heavily porous-coated diaphyseal-engaging cobalt-chromium stem. Over the next two years, radiographs demonstrate significant proximal femoral bone resorption. Which material property of the implant is primarily responsible for this phenomenon?

Explanation

Stress shielding occurs when a rigid implant with a high Young's modulus (high stiffness) bears the majority of the mechanical load instead of the surrounding bone. According to Wolff's law, this reduction in mechanical stress leads to proximal bone resorption.

Question 88

A comminuted tibial shaft fracture is treated with biological fixation using a submuscular bridge plate. Healing is expected to occur via robust callus formation. According to Perren's strain theory, what is the optimal interfragmentary strain environment for this type of secondary bone healing?

Explanation

Secondary bone healing characterized by cartilaginous callus formation occurs optimally at an interfragmentary strain of 2% to 10%. Strains less than 2% favor primary (osteonal) bone healing, whereas strains above 10% favor fibrous tissue formation or nonunion.

Question 89

A 45-year-old man presents with generalized bone pain and proximal muscle weakness. Laboratory evaluation reveals severe hypophosphatemia, hyperphosphaturia, normal serum calcium, and a normal parathyroid hormone level. Imaging identifies a small mesenchymal tumor in his thigh. Which hormone is most likely being overproduced?

Explanation

Tumor-induced osteomalacia is a paraneoplastic syndrome caused by excessive production of FGF23. FGF23 directly inhibits renal phosphate reabsorption and 1-alpha-hydroxylase activity, leading to isolated hypophosphatemia and inappropriately low active vitamin D levels.

Question 90

During biochemical analysis of a healthy intervertebral disc, distinct differences in extracellular matrix composition are noted between the annulus fibrosus and the nucleus pulposus. Which collagen type is the predominant structural protein in the annulus fibrosus?

Explanation

The annulus fibrosus consists predominantly of Type I collagen, which is highly organized to provide excellent tensile strength. In contrast, the nucleus pulposus is composed primarily of Type II collagen and proteoglycans to resist compressive forces.

Question 91

During mechanical testing of a human anterior cruciate ligament allograft, the specimen is stretched to a specific length and held constant over time. The researcher notes that the internal stress within the ligament steadily decreases over this period. This phenomenon describes which viscoelastic property?

Explanation

Stress relaxation is a defining viscoelastic property where the internal stress within a material decreases over time when it is held at a constant strain (length). Conversely, creep describes the gradual increase in strain (deformation) over time when subjected to a constant load.

Question 92

A surgeon elects to use demineralized bone matrix (DBM) to augment a posterolateral lumbar spinal fusion. Based on its biologic properties, which of the following accurately describes the healing potential of this graft material?

Explanation

Demineralized bone matrix (DBM) provides a collagen scaffold (osteoconductive) and retains bone morphogenetic proteins (BMPs) that stimulate local bone formation (osteoinductive). It does not contain live cells, so it lacks osteogenic properties.

Question 93

A 70-year-old woman is prescribed daily subcutaneous teriparatide injections for severe osteoporosis. What is the primary cellular mechanism by which intermittent administration of this agent increases bone mineral density?

Explanation

Teriparatide (recombinant human PTH 1-34) administered intermittently exerts an anabolic effect by directly stimulating osteoblast differentiation, activity, and lifespan while inhibiting their apoptosis. Continuous, high-level PTH exposure, conversely, would favor osteoclast-mediated bone resorption.

Question 94

During an internal fixation procedure, a resident accidentally uses a 316L stainless steel screw to secure a commercially pure titanium plate. Weeks later, aggressive corrosion is noted specifically where the screw head contacts the plate. What is the primary mechanism for this localized corrosion?

Explanation

Galvanic corrosion occurs when two dissimilar metals are placed in direct contact within an electrolytic medium (like body fluid). An electrochemical potential difference drives electron transfer, resulting in rapid dissolution of the less noble metal.

Question 95

An 8-year-old boy sustains a Salter-Harris Type II fracture of the distal femur. Through which specific microscopic zone of the physis does the fracture line classically propagate before exiting through the metaphysis?

Explanation

Salter-Harris fractures typically propagate through the zone of hypertrophy. This zone represents the mechanical weak point of the physis because it has a high ratio of cell volume to extracellular matrix.

Question 96

Skeletal muscle biopsy of the gastrocnemius in an elite marathon runner reveals a heavy predominance of Type I muscle fibers. Which of the following best characterizes the physiological properties of these fibers?

Explanation

Type I muscle fibers are slow-twitch, highly fatigue-resistant fibers that rely heavily on oxidative metabolism for sustained endurance. They are characterized by a high density of mitochondria, rich myoglobin content, and a dense capillary network.

Question 97

To significantly reduce abrasive and adhesive wear in total hip arthroplasty, highly cross-linked ultra-high-molecular-weight polyethylene (UHMWPE) is commonly utilized. However, the cross-linking process inherently sacrifices which of the following mechanical properties?

Explanation

High degrees of cross-linking vastly improve the wear resistance of UHMWPE. However, this process alters the polymer's internal structure, resulting in a clinically significant decrease in fatigue strength, ultimate tensile strength, and fracture toughness.

Question 98

Romosozumab is a potent anabolic agent utilized in osteoporosis treatment that works by neutralizing sclerostin. In normal bone biology, which cell type is the primary source of sclerostin secretion?

Explanation

Sclerostin is a glycoprotein secreted almost exclusively by mature osteocytes embedded within the mineralized matrix. It acts in a paracrine fashion to inhibit the Wnt/beta-catenin signaling pathway in osteoblasts, thereby suppressing bone formation.

Question 99

During tensile testing of a human flexor tendon, an initial non-linear 'toe region' is observed on the stress-strain curve at low strains (less than 2%). Which microscopic structural change directly accounts for this specific region?

Explanation

The 'toe region' represents the low-strain portion of the stress-strain curve in ligaments and tendons. It corresponds to the uncrimping or straightening of the naturally wavy, relaxed collagen fibers before they enter the linear elastic region.

Question 100

A surgeon applies recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) on a resorbable sponge to treat a recalcitrant nonunion. Which intracellular signaling pathway is primarily activated when rhBMP-2 binds to its target cell surface receptor?

Explanation

Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily. They exert their osteoinductive effects by binding to specific cell surface serine/threonine kinase receptors, which subsequently phosphorylate and activate intracellular Smad proteins (primarily Smads 1, 5, and 8) to drive osteogenic transcription.

AAOS & ABOS Basic Science MCQs (Set 3): Bone Biology, Biomechanics & Anatomy Review

AAOS & ABOS Basic Science MCQs (Set 4): Bone Biology, Biomechanics & Physiology | Orthopedic Board Prep

Key Takeaway

AAOS & ABOS Basic Science MCQs (Set 4): Bone Biology, Biomechanics & Physiology | Orthopedic Board Prep

Chapter Index