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Biology, Genetics & Bone Healing MCQs

Practice Set 67 of 212

This practice set contains high-yield board review questions covering key concepts in Biology, Genetics & Bone Healing. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 1321

Topic: Biology, Genetics & Bone Healing

A 3-year-old girl with blue sclerae and dentinogenesis imperfecta presents with her third low-energy long bone fracture. Genetic testing confirms a mutation affecting type I collagen. Which of the following systemic pharmacological treatments is most commonly indicated to decrease fracture incidence and improve bone mass in this condition?

. Recombinant human growth hormone
. Intravenous pamidronate
. Oral calcium and vitamin D supplementation only
. Teriparatide
. Denosumab

Correct Answer & Explanation

. Recombinant human growth hormone

Explanation

The patient's clinical presentation and genetic defect are consistent with Osteogenesis Imperfecta (OI). Intravenous bisphosphonates, such as pamidronate or zoledronic acid, are the current gold standard medical therapy for moderate to severe pediatric OI. By inhibiting osteoclast-mediated bone resorption, bisphosphonates increase bone mineral density, decrease the frequency of fractures, and often alleviate chronic bone pain. Teriparatide is generally contraindicated in children with open physes.

Question 1322

Topic: Biology, Genetics & Bone Healing

A 68-year-old woman with a 9-year history of alendronate therapy reports an insidious onset of right thigh pain. Radiographs reveal focal lateral cortical thickening of the proximal femoral diaphysis with a subtle, transverse radiolucent line extending through the lateral cortex. What is the most appropriate management?

. Discontinue alendronate and prescribe strict bed rest for 6 weeks
. Switch to denosumab and allow weight-bearing as tolerated
. Prophylactic open reduction and internal fixation with a dynamic hip screw
. Prophylactic stabilization with a cephalomedullary nail
. Core decompression of the proximal femur

Correct Answer & Explanation

. Discontinue alendronate and prescribe strict bed rest for 6 weeks

Explanation

This patient has an impending atypical femur fracture (AFF) associated with long-term bisphosphonate use. Because she has prodromal thigh pain and a visible transverse radiolucent line, prophylactic fixation with a cephalomedullary nail is indicated to prevent completion of the fracture.

Question 1323

Topic: Biology, Genetics & Bone Healing

A 68-year-old woman with a 10-year history of daily alendronate use presents with progressive, severe right thigh pain with weight-bearing. Radiographs demonstrate focal lateral cortical thickening (beaking) and a transverse radiolucent line involving 60% of the lateral cortex in the subtrochanteric region. What is the most appropriate management?

. Discontinue alendronate and observe with protected weight-bearing
. Core decompression of the proximal femur
. Prophylactic cephalomedullary nailing of the right femur
. Sliding hip screw fixation
. Prescribe teriparatide and restrict weight-bearing indefinitely

Correct Answer & Explanation

. Discontinue alendronate and observe with protected weight-bearing

Explanation

This patient has a symptomatic, incomplete atypical femur fracture due to prolonged bisphosphonate use. Because she has prodromal pain and the radiolucency involves a significant portion of the cortex, prophylactic intramedullary nailing is indicated to prevent completion of the fracture.

Question 1324

Topic: Biology, Genetics & Bone Healing

A 68-year-old woman on long-term bisphosphonate therapy presents with weeks of vague anterior thigh pain, followed by an acute inability to bear weight. Radiographs show a transverse subtrochanteric fracture with lateral cortical thickening. What is the underlying mechanism of this atypical fracture?

. Overactivation of osteoclasts leading to focal osteolysis
. Severe vitamin D deficiency impairing mineralization
. Suppression of targeted bone remodeling and accumulation of microdamage
. Reduced osteoblast differentiation from marrow stromal cells
. Increased inflammatory cytokines promoting rapid bone turnover

Correct Answer & Explanation

. Overactivation of osteoclasts leading to focal osteolysis

Explanation

Long-term bisphosphonate use heavily suppresses osteoclast-mediated targeted bone remodeling. This suppression prevents the repair of physiologic wear and tear, leading to an accumulation of microdamage, brittle bone, and atypical subtrochanteric or diaphyseal fractures.

Question 1325

Topic: Biology, Genetics & Bone Healing

A 70-year-old woman on long-term alendronate therapy reports a 3-month history of vague thigh pain. Radiographs reveal lateral cortical thickening and a transverse radiolucent line in the subtrochanteric region. What is the most appropriate prophylactic surgical management for this impending fracture?

. Lateral closing wedge osteotomy
. Cephalomedullary nail fixation
. Plating with a broad dynamic compression plate
. Discontinuation of bisphosphonates without surgical intervention
. Teriparatide therapy alone

Correct Answer & Explanation

. Lateral closing wedge osteotomy

Explanation

For impending atypical femoral fractures associated with prolonged bisphosphonate use (manifesting as lateral thigh pain and cortical beaking/radiolucency), prophylactic fixation with a cephalomedullary nail is recommended. The bisphosphonate should also be immediately discontinued.

Question 1326

Topic: Biology, Genetics & Bone Healing

A 68-year-old woman on long-term alendronate for osteoporosis presents with a 3-month history of prodromal anterior thigh pain.

Radiographs demonstrate a transverse, nondisplaced radiolucency in the lateral cortex of the subtrochanteric region with localized periosteal "beaking." What is the most appropriate next step in management?

. Discontinue alendronate and prescribe protected weight-bearing with crutches
. Immediate prophylactic cephalomedullary nailing
. Corticosteroid injection into the trochanteric bursa
. Core decompression of the proximal femur
. Convert to teriparatide therapy and monitor with serial radiographs every 6 months

Correct Answer & Explanation

. Discontinue alendronate and prescribe protected weight-bearing with crutches

Explanation

The patient exhibits classic clinical and radiographic signs of an impending atypical femoral fracture secondary to prolonged bisphosphonate therapy. Given the presence of prodromal thigh pain and cortical beaking, prophylactic cephalomedullary nailing is indicated to prevent catastrophic completion of the fracture.

Question 1327

Topic: Biology, Genetics & Bone Healing

Following surgical fixation of an osteoporotic intertrochanteric hip fracture, when is the optimal time to initiate intravenous zoledronic acid to reduce the risk of subsequent fractures without delaying fracture union?

. Within 24 hours of surgery
. 1 week postoperatively
. 2 to 6 weeks postoperatively
. 3 months postoperatively
. 6 months postoperatively

Correct Answer & Explanation

. Within 24 hours of surgery

Explanation

Initiation of bisphosphonate therapy is typically recommended within 2 to 6 weeks postoperatively. This slight delay allows the initial fracture callus to form without disruption, while still significantly reducing future fracture risk.

Question 1328

Topic: Biology, Genetics & Bone Healing

A 45-year-old male sustains a closed transverse midshaft humerus fracture. He is treated with open reduction and internal fixation using a dynamic compression plate, achieving absolute stability with an interfragmentary gap of less than 0.1 mm.

What is the primary mode of bone healing expected in this construct?

. Secondary healing via endochondral ossification
. Primary healing via cutting cone remodeling
. Intramembranous ossification from the periosteum
. Fibrous nonunion due to stress shielding
. Creeping substitution

Correct Answer & Explanation

. Secondary healing via endochondral ossification

Explanation

Absolute stability with a gap < 1mm and strain < 2% results in primary bone healing. This occurs via Haversian remodeling where osteoclastic cutting cones cross the fracture site followed immediately by osteoblasts laying down new bone.

Question 1329

Topic: Biology, Genetics & Bone Healing

Which of the following molecules acts as an antagonist of the Wnt/beta-catenin signaling pathway, thereby inhibiting osteoblastogenesis and bone formation?

. Bone morphogenetic protein-2 (BMP-2)
. Sclerostin
. Osteoprotegerin (OPG)
. Receptor activator of nuclear factor kappa-B ligand (RANKL)
. Transforming growth factor-beta (TGF-b)

Correct Answer & Explanation

. Bone morphogenetic protein-2 (BMP-2)

Explanation

Sclerostin, produced primarily by osteocytes, binds to LRP5/6 receptors and inhibits the Wnt/beta-catenin pathway, thereby decreasing osteoblast differentiation and bone formation. Monoclonal antibodies targeting sclerostin (e.g., romosozumab) are used to treat osteoporosis.

Question 1330

Topic: Biology, Genetics & Bone Healing

Distraction osteogenesis fundamentally relies on the biological principle of the tension-stress effect. What is the predominant type of bone formation seen in the distraction gap under optimal conditions?

. Endochondral ossification
. Intramembranous ossification
. Primary bone healing
. Appositional chondrogenesis
. Fibrous metaplasia

Correct Answer & Explanation

. Endochondral ossification

Explanation

Under conditions of optimal mechanical stability and a correct distraction rate (typically 1 mm/day), the tension-stress effect stimulates bone formation directly from osteoblasts without a cartilaginous intermediate, known as intramembranous ossification.

Question 1331

Topic: Biology, Genetics & Bone Healing

Bone morphogenetic proteins (BMPs), such as BMP-2 and BMP-7, initiate osteoblast differentiation by binding to specific heterodimeric cell surface receptors. These receptors primarily function as:

. G-protein coupled receptors
. Tyrosine kinases
. Serine-threonine kinases
. Ligand-gated ion channels
. Nuclear hormone receptors

Correct Answer & Explanation

. G-protein coupled receptors

Explanation

BMP receptors are transmembrane serine-threonine kinases. Upon ligand binding, they form a complex that phosphorylates intracellular Smad proteins, which then translocate to the nucleus to regulate target gene transcription.

Question 1332

Topic: Biology, Genetics & Bone Healing

According to Perren's strain theory, what level of local interfragmentary strain is required to allow for primary bone healing (osteonal remodeling without visible callus)?

. < 2%
. 2% to 10%
. 10% to 30%
. > 30%
. Strain level does not affect primary bone healing

Correct Answer & Explanation

. < 2%

Explanation

Primary bone healing requires absolute stability with an interfragmentary strain of less than 2%. Strains between 2% and 10% promote secondary bone healing via callus formation, while strains greater than 10% typically lead to nonunion.

Question 1333

Topic: Biology, Genetics & Bone Healing

Bone morphogenetic proteins (BMPs) initiate intracellular signaling upon binding to serine/threonine kinase receptors. Which of the following intracellular proteins are directly phosphorylated and translocate to the nucleus to regulate gene expression?

. JAK and STAT
. beta-catenin
. SMAD 1, 5, and 8
. NF-kappa B
. MAP kinases

Correct Answer & Explanation

. JAK and STAT

Explanation

BMP signaling is primarily mediated through the canonical SMAD pathway. Upon receptor activation, receptor-regulated SMADs (SMAD 1, 5, and 8) are phosphorylated and form a complex with SMAD 4 to enter the nucleus and regulate osteogenic genes.

Question 1334

Topic: Biology, Genetics & Bone Healing

Sclerostin is a potent inhibitor of bone formation that functions by antagonizing the Wnt/beta-catenin signaling pathway. Which cell type is the primary source of sclerostin in mature bone?

. Osteoblasts
. Osteoclasts
. Osteocytes
. Chondrocytes
. Mesenchymal stem cells

Correct Answer & Explanation

. Osteoblasts

Explanation

Osteocytes embedded in the bone matrix synthesize and secrete sclerostin, which actively inhibits osteoblastic bone formation. Monoclonal antibodies targeting sclerostin (e.g., romosozumab) are used clinically to promote bone formation in severe osteoporosis.

Question 1335

Topic: Biology, Genetics & Bone Healing

Osteoclast differentiation and activation are heavily regulated by the RANK/RANKL/OPG axis. Osteoprotegerin (OPG) exerts its regulatory effect by:

. Binding to RANK on the osteoclast precursor to stimulate differentiation
. Acting as a decoy receptor binding to RANKL, preventing it from interacting with RANK
. Directly inducing apoptosis of mature multinucleated osteoclasts
. Cleaving the RANK receptor from the surface of osteoblasts
. Binding to M-CSF to inhibit the initial proliferation of macrophages

Correct Answer & Explanation

. Binding to RANK on the osteoclast precursor to stimulate differentiation

Explanation

OPG is secreted by osteoblasts and acts as a soluble decoy receptor for RANKL. By effectively binding RANKL, OPG prevents it from interacting with RANK on osteoclast precursors, thereby inhibiting osteoclastogenesis and bone resorption.

Question 1336

Topic: Biology, Genetics & Bone Healing

Recombinant human bone morphogenetic protein-2 (rhBMP-2) signals primarily through which of the following intracellular pathways to promote osteoblast differentiation?

. Wnt/beta-catenin pathway
. RANKL/NF-kappaB pathway
. Smad 1/5/8 pathway
. Notch signaling pathway
. JAK/STAT pathway

Correct Answer & Explanation

. Wnt/beta-catenin pathway

Explanation

Bone morphogenetic proteins (BMPs) bind to serine/threonine kinase receptors and primarily exert their intracellular effects via the Smad 1/5/8 signaling pathway. This upregulates osteoblast differentiation factors like Runx2.

Question 1337

Topic: Biology, Genetics & Bone Healing

Distraction osteogenesis typically relies on which of the following mechanisms for new bone formation?

. Endochondral ossification
. Intramembranous ossification
. Primary bone healing
. Appositional bone growth
. Chondrocyte hypertrophy without ossification

Correct Answer & Explanation

. Endochondral ossification

Explanation

Distraction osteogenesis predominantly proceeds via intramembranous ossification. In this process, bone forms directly from mesenchymal cells without a pre-existing cartilage intermediate.

Question 1338

Topic: Biology, Genetics & Bone Healing

Which of the following components of articular cartilage is primarily responsible for its ability to resist compressive loads?

. Type I collagen
. Type II collagen
. Aggrecan
. Elastin
. Hyaluronidase

Correct Answer & Explanation

. Type I collagen

Explanation

Aggrecan, the major proteoglycan in articular cartilage, possesses highly negatively charged glycosaminoglycan chains. These chains draw water into the tissue, creating swelling pressure that effectively resists compressive loads.

Question 1339

Topic: Biology, Genetics & Bone Healing

During fracture healing, the peak of soft callus formation typically correlates with the maximum expression of which collagen type?

. Type I
. Type II
. Type III
. Type IV
. Type X

Correct Answer & Explanation

. Type I

Explanation

The soft callus stage of secondary bone healing is characterized by the formation of fibrocartilage. This stage is associated with a peak expression of Type II collagen.

Question 1340

Topic: Biology, Genetics & Bone Healing

Osteoprotegerin (OPG) functions to inhibit osteoclastogenesis by binding directly to which of the following molecules?

. RANK receptor
. RANK ligand (RANKL)
. Macrophage colony-stimulating factor (M-CSF)
. Calcitonin receptor
. Sclerostin

Correct Answer & Explanation

. RANK receptor

Explanation

Osteoprotegerin acts as a decoy receptor that binds directly to RANKL. By preventing RANKL from binding to its receptor (RANK) on osteoclast precursors, OPG inhibits osteoclast differentiation and activation.

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