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1. General Principles & Basic Science MCQs

Practice Set 752 of 789

This practice set contains high-yield board review questions covering key concepts in 1. General Principles & Basic Science. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 15021

Topic: 1. General Principles & Basic Science
A 14-year-old boy with severe hemophilia A requires an elective orthopedic procedure. Preoperative laboratory testing reveals a high-titer factor VIII inhibitor (>5 Bethesda units). Which of the following is the most appropriate management to ensure perioperative hemostasis?
. Continuous high-dose factor VIII infusion
. Desmopressin (DDAVP)
. Recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC)
. Fresh frozen plasma infusion
. Cryoprecipitate infusion

Correct Answer & Explanation

. Recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC)

Explanation

Patients with high-titer inhibitors (>5 BU) fail to respond to standard factor VIII replacement due to rapid neutralization. Bypassing agents, such as recombinant factor VIIa or aPCC (FEIBA), are required to achieve hemostasis.

Question 15022

Topic: 1. General Principles & Basic Science

In a patient with severe hemophilia, recurrent hemarthroses inevitably lead to end-stage hemophilic arthropathy. What is the primary mediator of the initial synovial hypertrophy and subsequent cartilage destruction in this disease process?

. Autoantibody formation against Type II collagen
. Uric acid crystal deposition in the joint space
. Hemosiderin deposition from erythrocyte breakdown
. Direct viral infection of the synovial lining
. Ischemic necrosis of the subchondral bone plate

Correct Answer & Explanation

. Hemosiderin deposition from erythrocyte breakdown

Explanation

Recurrent bleeding into the joint leads to the accumulation of iron/hemosiderin from red blood cell breakdown. Iron accumulation induces marked synovial hypertrophy, chronic inflammation, and direct chondrocyte toxicity.

Question 15023

Topic: Biology, Genetics & Bone Healing

A 72-year-old woman who has taken alendronate for 8 years sustains a low-energy transverse subtrochanteric femur fracture. Radiographs show lateral cortical thickening and a medial spike. Along with surgical fixation, what is the most appropriate long-term management of her bone health?

. Continue alendronate and maximize calcium/Vitamin D
. Discontinue alendronate and initiate teriparatide
. Discontinue alendronate and initiate denosumab
. Increase the dose of alendronate to promote healing
. Switch from alendronate to intravenous zoledronic acid

Correct Answer & Explanation

. Discontinue alendronate and initiate teriparatide

Explanation

The patient sustained an atypical femur fracture (AFF) due to severe suppression of bone turnover from long-term bisphosphonate use. Bisphosphonates must be stopped, and an anabolic agent like teriparatide (recombinant PTH) should be initiated to stimulate bone formation.

Question 15024

Topic: Biology, Genetics & Bone Healing

A 30-year-old woman presents with an expansile, lytic, epiphyseal lesion of the proximal tibia. Biopsy confirms Giant Cell Tumor (GCT) of bone. Denosumab is planned to aid in joint preservation. Denosumab acts primarily by inhibiting which of the following?

. Receptor activator of nuclear factor kappa-B ligand (RANKL)
. Osteoprotegerin (OPG)
. Cathepsin K
. Sclerostin
. Vascular Endothelial Growth Factor (VEGF)

Correct Answer & Explanation

. Receptor activator of nuclear factor kappa-B ligand (RANKL)

Explanation

Denosumab is a monoclonal antibody that binds to and inhibits RANKL. In GCT, the neoplastic stromal cells express RANKL, which recruits and activates the reactive osteoclast-like giant cells that cause bone destruction.

Question 15025

Topic: Biology, Genetics & Bone Healing

A 12-year-old boy presents with short stature, waddling gait, and early-onset osteoarthritis of the hips. Radiographs demonstrate irregular, delayed ossification of the capital femoral epiphyses and a double-layered patella. A mutation in which of the following genes is most likely responsible?

. COL1A1
. COMP
. FGFR3
. RUNX2
. SOX9

Correct Answer & Explanation

. COMP

Explanation

Multiple Epiphyseal Dysplasia (MED) is characterized by delayed epiphyseal ossification and double-layered patellae. The most common autosomal dominant form is caused by a mutation in the Cartilage Oligomeric Matrix Protein (COMP) gene.

Question 15026

Topic: Biology, Genetics & Bone Healing

A 6-year-old girl is evaluated for delayed dental eruption and abnormal shoulder mobility. Physical examination reveals the ability to approximate her shoulders anteriorly to the midline. Cranial sutures are widened. A defect in which of the following transcription factors is responsible for this condition?

. RUNX2 (CBFA1)
. FGFR3
. SOX9
. COMP
. EXT1

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is characterized by hypoplastic or absent clavicles, delayed cranial suture closure, and dental anomalies. It is caused by an autosomal dominant mutation in the RUNX2 (CBFA1) gene, which is a master transcription factor for osteoblast differentiation.

Question 15027

Topic: Biology, Genetics & Bone Healing

A 4-year-old child with blue sclerae, dentinogenesis imperfecta, and multiple long bone fractures is diagnosed with Osteogenesis Imperfecta (OI). Intravenous bisphosphonate therapy is initiated to reduce fracture burden. What is the primary cellular mechanism of action of this medication?

. Stimulation of osteoblast bone formation
. Inhibition of osteoclast-mediated bone resorption
. Provision of exogenous Type I collagen
. Enhancement of intestinal calcium absorption
. Suppression of parathyroid hormone secretion

Correct Answer & Explanation

. Inhibition of osteoclast-mediated bone resorption

Explanation

Bisphosphonates, such as pamidronate or zoledronic acid, reduce fracture rates in OI by inhibiting osteoclast-mediated bone resorption. This increases cortical thickness and bone mass, despite the underlying defect in Type I collagen synthesis.

Question 15028

Topic: Biology, Genetics & Bone Healing
A neonate is born with disproportionate short-trunk dwarfism, a barrel chest, and cleft palate. Radiographs show severe coxa vara and delayed ossification of the epiphyses. An ophthalmologic exam reveals severe myopia. This clinical picture is most consistent with spondyloepiphyseal dysplasia congenita (SEDC). Which structural protein is primarily defective?
. Type I collagen
. Type II collagen
. Type III collagen
. Type IV collagen
. Type X collagen

Correct Answer & Explanation

. Type II collagen

Explanation

SEDC is a type II collagenopathy caused by mutations in the COL2A1 gene. Since type II collagen is the primary structural protein in articular cartilage and the vitreous humor of the eye, patients present with epiphyseal dysplasia, short trunk, and severe visual problems like myopia or retinal detachment.

Question 15029

Topic: Biology, Genetics & Bone Healing

A 55-year-old female presents with severe pain, swelling, and stiffness of the hand 6 weeks after a distal radius fracture.

Which of the following prophylactic treatments has been shown to reduce the incidence of this complication if initiated acutely following the fracture?

. Vitamin D
. Calcium carbonate
. Vitamin C
. Teriparatide
. Gabapentin

Correct Answer & Explanation

. Vitamin C

Explanation

The patient has Complex Regional Pain Syndrome (CRPS). Vitamin C (500 mg daily) has been shown to decrease the risk of developing CRPS when given early following a distal radius fracture.

Question 15030

Topic: Biology, Genetics & Bone Healing

A 10-year-old girl is able to bring her shoulders together anteriorly in the midline and exhibits delayed eruption of secondary teeth. What is the expected inheritance pattern and affected gene for this condition?

. Autosomal recessive; CBFA1 (RUNX2)
. Autosomal dominant; CBFA1 (RUNX2)
. Autosomal dominant; COL1A1
. X-linked recessive; DMD
. Autosomal recessive; FGFR3

Correct Answer & Explanation

. Autosomal dominant; CBFA1 (RUNX2)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the CBFA1 (RUNX2) gene, crucial for osteoblast differentiation. It classically features hypoplastic clavicles and delayed dental eruption.

Question 15031

Topic: Biology, Genetics & Bone Healing

A child presents with frequent fractures, cranial nerve palsies, and hepatosplenomegaly. Radiographs show a generalized bone-in-bone appearance. The pathophysiology of this disease is primarily related to a defect in which of the following?

. Osteoblast matrix production
. Osteoclast ruffled border function
. Endochondral ossification at the physis
. Intramembranous ossification
. Mineralization of osteoid

Correct Answer & Explanation

. Osteoclast ruffled border function

Explanation

Osteopetrosis is caused by defective osteoclastic bone resorption, often due to a failure to form the ruffled border or a defect in carbonic anhydrase II. This leads to excessively dense but highly brittle bone.

Question 15032

Topic: Biology, Genetics & Bone Healing

A 30-year-old female presents with knee pain. Radiographs show an eccentric, purely lytic epiphyseal lesion extending to the subchondral bone without a sclerotic rim. Biopsy confirms Giant Cell Tumor. Which medication targets the underlying molecular driver of the neoplastic cells?

. Imatinib
. Denosumab
. Bisphosphonates
. Methotrexate
. Doxorubicin

Correct Answer & Explanation

. Denosumab

Explanation

In Giant Cell Tumor of bone, the neoplastic stromal cells express RANKL, which recruits bone-resorbing osteoclast-like giant cells. Denosumab, a monoclonal antibody against RANKL, inhibits this process.

Question 15033

Topic: Biology, Genetics & Bone Healing

A 32-year-old woman presents with knee pain. Radiographs reveal an eccentric, lytic lesion in the distal femur extending to the subchondral bone without a sclerotic margin. A biopsy confirms multinucleated giant cells. Which medication is an FDA-approved targeted therapy for unresectable or recurrent cases of this tumor?

. Imatinib
. Denosumab
. Rituximab
. Bevacizumab
. Methotrexate

Correct Answer & Explanation

. Denosumab

Explanation

Giant Cell Tumor of bone consists of neoplastic stromal cells that express RANKL, stimulating the recruitment of osteoclast-like giant cells. Denosumab, a monoclonal antibody against RANKL, is an effective treatment for unresectable or recurrent GCT.

Question 15034

Topic: Biology, Genetics & Bone Healing

A 65-year-old man with a known history of Paget's disease of bone sustains a subtrochanteric femur fracture after a minor fall. What is the most common underlying cause of increased bone turnover in this disease?

. Defective osteoblast mineralization
. Excessive osteoclastic bone resorption followed by disorganized osteoblast bone formation
. Overproduction of parathyroid hormone
. Deficient type I collagen synthesis
. Mutation in the FGF23 gene

Correct Answer & Explanation

. Excessive osteoclastic bone resorption followed by disorganized osteoblast bone formation

Explanation

Paget's disease is characterized by an initial phase of excessive and chaotic osteoclastic bone resorption. This is followed by a compensatory, disorganized osteoblastic bone formation resulting in structurally weak woven bone prone to fractures.

Question 15035

Topic: Biology, Genetics & Bone Healing

A 72-year-old woman on long-term alendronate therapy for osteoporosis presents with atraumatic thigh pain. Radiographs reveal focal cortical thickening and a transverse radiolucent line on the lateral cortex of the subtrochanteric femur. What is the recommended management?

. Continued observation with non-weight bearing
. Teriparatide therapy and prophylactic intramedullary nailing
. Corticosteroid injection
. Switch to denosumab
. Plate fixation and bone grafting

Correct Answer & Explanation

. Teriparatide therapy and prophylactic intramedullary nailing

Explanation

Atypical femur fractures are associated with prolonged bisphosphonate use. Patients with an impending fracture (lateral cortical 'beaking' and pain) should undergo prophylactic intramedullary nailing, and anabolic agents like teriparatide may be initiated.

Question 15036

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with short stature, rhizomelic shortening of the limbs, and frontal bossing. Radiographs show narrowing of the interpedicular distances in the lumbar spine. Based on the classification of skeletal dysplasias with predominantly metaphyseal involvement, which of the following genetic mutations is most likely responsible for this condition?

. COL1A1
. FGFR3
. COMP
. RUNX2
. SOX9

Correct Answer & Explanation

. FGFR3

Explanation

Correct Answer: FGFR3Achondroplasia is the most common form of short-limb dwarfism and is classified as a skeletal dysplasia with predominantly metaphyseal involvement. It is caused by an autosomal dominant, activating mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene, which inhibits endochondral ossification.

Question 15037

Topic: Biology, Genetics & Bone Healing

A 6-year-old girl is brought to the clinic with a history of multiple low-energy fractures. Examination reveals blue sclerae and dentinogenesis imperfecta. Which of the following best describes the underlying pathophysiology of her condition?

. Defect in endochondral ossification
. Defective synthesis of type I collagen
. Impaired osteoclast function
. Mutation in the fibroblast growth factor receptor 3
. Defective mineralization of osteoid

Correct Answer & Explanation

. Defective synthesis of type I collagen

Explanation

Correct Answer: Defective synthesis of type I collagenOsteogenesis Imperfecta is a skeletal dysplasia characterized by abnormalities of bone density and modeling defects. It is caused by quantitative or qualitative defects in type I collagen, typically due to mutations in the COL1A1 or COL1A2 genes, leading to bone fragility, blue sclerae, and hearing loss.

Question 15038

Topic: Infection, Pharmacology & VTE

A 7-year-old boy presents with a 3-day history of fever, malaise, and severe pain in his right distal femur. He refuses to bear weight. Laboratory tests show elevated CRP and ESR. In acute hematogenous pyogenic osteomyelitis in children, what is the most common anatomic location for the initial nidus of infection?

. Diaphysis
. Epiphysis
. Metaphysis
. Apophysis
. Articular cartilage

Correct Answer & Explanation

. Metaphysis

Explanation

Correct Answer: MetaphysisAcute hematogenous pyogenic osteomyelitis in children most commonly begins in the metaphysis of long bones. This is due to the sluggish blood flow in the venous sinusoids of the metaphyseal region, which provides an ideal environment for bacterial seeding and proliferation.

Question 15039

Topic: Biology, Genetics & Bone Healing

A 12-year-old girl is evaluated for delayed dental eruption and the ability to bring her shoulders together anteriorly. Radiographs show absent clavicles and delayed ossification of the pubic symphysis. What is the inheritance pattern and associated gene mutation for this syndrome?

. Autosomal dominant, RUNX2 (CBFA1)
. Autosomal recessive, RUNX2 (CBFA1)
. X-linked recessive, PHEX
. Autosomal dominant, FGFR2
. Autosomal recessive, ALPL

Correct Answer & Explanation

. Autosomal dominant, RUNX2 (CBFA1)

Explanation

Correct Answer: Autosomal dominant, RUNX2 (CBFA1)The patient has Cleidocranial Dysplasia, characterized by hypoplastic or absent clavicles, delayed closure of cranial sutures, delayed dental eruption, and widened pubic symphysis. It is an autosomal dominant condition caused by a mutation in the RUNX2 (also known as CBFA1) gene. This gene is a critical transcription factor for osteoblast differentiation and bone formation.

Question 15040

Topic: Biology, Genetics & Bone Healing

A 32-year-old female presents with knee pain. Radiographs show an eccentric, lytic epiphyseal-metaphyseal lesion in the distal femur extending to the subchondral bone. Biopsy reveals multinucleated giant cells in a background of mononuclear stromal cells. Which of the following targeted therapies is most appropriate for unresectable or recurrent cases of this tumor?

. Imatinib
. Denosumab
. Rituximab
. Infliximab
. Teriparatide

Correct Answer & Explanation

. Denosumab

Explanation

Correct Answer: DenosumabGiant Cell Tumor (GCT) of bone is characterized by neoplastic mononuclear stromal cells that express RANKL. This RANKL recruits and activates osteoclast-like multinucleated giant cells, leading to extensive bone resorption. Denosumab is a monoclonal antibody that binds to RANKL, inhibiting this pathway. It is highly effective and FDA-approved for the treatment of GCTs that are unresectable or where surgery would result in severe morbidity.

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