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Biology, Genetics & Bone Healing MCQs

Practice Set 4 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 61

Topic: Biology, Genetics & Bone Healing
A 5-year-old boy presents with anterolateral bowing of the tibia and multiple café-au-lait macules. Radiographs demonstrate diaphyseal narrowing and a pseudarthrosis. What is the primary underlying cellular defect in the pseudarthrosis tissue?
. Increased osteoclast activity and deficient osteoblast function
. Overexpression of fibroblast growth factor receptor 3 (FGFR3)
. Mutation in the COL1A1 gene
. Absent dystrophin protein
. Accumulation of mucopolysaccharides

Correct Answer & Explanation

. Increased osteoclast activity and deficient osteoblast function

Explanation

Congenital pseudarthrosis of the tibia in Neurofibromatosis Type 1 (NF1) is driven by a local loss of neurofibromin. This leads to increased osteoclast activity and diminished osteoblast function in the local hamartomatous tissue.

Question 62

Topic: Biology, Genetics & Bone Healing

Which of the following agents is contraindicated in children with open physes:

. Pamidronate
. Alendronate
. Etidronate
. Teriparatide
. C alcium carbonate

Correct Answer & Explanation

. Teriparatide

Explanation

Teriparatide, or Forteo (Eli Lilly and C ompany, Indianapolis, Ind), is contraindicated in children with open physes because of a concern for the risk of osteosarcoma.

Question 63

Topic: Biology, Genetics & Bone Healing
A 9-year-old girl presents with precocious puberty, café-au-lait spots with irregular borders, and multiple lytic bone lesions with a ground-glass appearance. The pathogenesis of this condition is most directly related to a mutation in which of the following?
. GNAS1 gene leading to increased cAMP
. EXT1 gene leading to decreased heparan sulfate
. SQSTM1 gene leading to increased osteoclast activity
. FGFR3 gene leading to defective endochondral ossification
. RUNX2 gene leading to defective osteoblast differentiation

Correct Answer & Explanation

. GNAS1 gene leading to increased cAMP

Explanation

McCune-Albright syndrome is caused by a sporadic, post-zygotic activating mutation in the GNAS1 gene. This leads to continuous activation of adenylyl cyclase and increased intracellular cAMP, affecting multiple endocrine and skeletal tissues.

Question 64

Topic: Biology, Genetics & Bone Healing

A 65-year-old man of European descent presents with deep, aching pain in his right pelvis and thigh, accompanied by increasing head size. Laboratory studies show normal serum calcium, normal phosphorus, and markedly elevated alkaline phosphatase.

Which gene mutation is most strongly associated with the familial form of this disease?

. GNAS1
. SQSTM1
. EXT1
. RUNX2
. COL1A1

Correct Answer & Explanation

. SQSTM1

Explanation

The patient has Paget's disease of bone, characterized by isolated elevated alkaline phosphatase and bone enlargement. Mutations in the SQSTM1 (p62) gene are present in up to 30% of familial Paget's disease cases, leading to increased osteoclast activity.

Question 65

Topic: Biology, Genetics & Bone Healing

A 55-year-old female with symptomatic Paget's disease of the femur is started on a nitrogen-containing bisphosphonate (e.g., zoledronate). What is the primary molecular mechanism of action of this medication in treating her condition?

. Inhibition of the RANKL pathway
. Inhibition of farnesyl pyrophosphate synthase in the mevalonate pathway
. Direct stimulation of osteoblast apoptosis
. Binding to hydroxyapatite and increasing osteoclast proliferation
. Inhibition of adenylyl cyclase

Correct Answer & Explanation

. Inhibition of farnesyl pyrophosphate synthase in the mevalonate pathway

Explanation

Nitrogen-containing bisphosphonates inhibit farnesyl pyrophosphate synthase within the osteoclast mevalonate pathway. This prevents protein prenylation, causing osteoclast apoptosis and drastically reducing the hyperactive bone resorption seen in Paget's disease.

Question 66

Topic: Biology, Genetics & Bone Healing

In Paget's disease of bone, which of the following phases is characterized by a pathognomonic "mosaic" pattern of lamellar bone with prominent cement lines upon histological examination?

. The initial osteolytic phase
. The mixed osteoclastic-osteoblastic phase
. The late osteosclerotic (inactive) phase
. The malignant transformation phase
. The inflammatory phase

Correct Answer & Explanation

. The late osteosclerotic (inactive) phase

Explanation

The late osteosclerotic (or burnt-out) phase of Paget's disease features dense, hypovascular bone with a disorganized "mosaic" or "jigsaw puzzle" pattern of prominent cement lines. This results from chaotic, rapid bone remodeling during the preceding mixed phase.

Question 67

Topic: Biology, Genetics & Bone Healing

A 30-year-old patient with polyostotic fibrous dysplasia complains of intractable bone pain in the pelvis and lower extremities. Which of the following is the most appropriate initial medical therapy?

. Oral calcium and Vitamin D
. Intravenous pamidronate
. Subcutaneous denosumab
. Oral methotrexate
. Oral indomethacin

Correct Answer & Explanation

. Intravenous pamidronate

Explanation

Intravenous bisphosphonates, such as pamidronate, are considered the medical treatment of choice for alleviating bone pain and reducing the rate of osteoclastic resorption in polyostotic fibrous dysplasia.

Question 68

Topic: Biology, Genetics & Bone Healing

A 35-year-old female presents with an unresectable giant cell tumor of the sacrum. Which of the following targeted biologic therapies is most appropriate?

. Imatinib
. Denosumab
. Bevacizumab
. Rituximab
. Trastuzumab

Correct Answer & Explanation

. Denosumab

Explanation

Denosumab is a monoclonal antibody against RANKL. It is FDA-approved for adults and skeletally mature adolescents with giant cell tumors of bone that are unresectable or where surgical resection would cause severe morbidity.

Question 69

Topic: Biology, Genetics & Bone Healing

A 3-year-old boy presents with anterior bowing of his tibia. Radiographs show a well-circumscribed, intracortical osteolytic lesion involving the anterior tibial diaphysis. Biopsy reveals benign fibrous tissue with woven bone trabeculae lined by prominent osteoblasts. What is the most appropriate initial management?

. Wide en bloc resection
. Curettage and bone grafting
. Observation alone
. Intramedullary nailing
. Radiation therapy

Correct Answer & Explanation

. Observation alone

Explanation

Osteofibrous dysplasia (Campanacci disease) typically affects the anterior cortex of the tibia in young children. Observation is the standard of care as most lesions stabilize or regress after skeletal maturity.

Question 70

Topic: Biology, Genetics & Bone Healing

A 16-year-old boy undergoes a biopsy of a solitary radiolucent lesion in the proximal femur with a 'ground-glass' matrix. The histological evaluation demonstrates trabeculae of woven bone in a fibrous stroma.

Which of the following classically distinguishes this lesion from normal woven bone formation?

. Presence of Birbeck granules
. Prominent osteoblastic rimming
. Absence of osteoblastic rimming
. Cartilaginous cap formation
. Abundant multinucleated giant cells

Correct Answer & Explanation

. Absence of osteoblastic rimming

Explanation

Fibrous dysplasia is histologically characterized by irregular trabeculae of woven bone (Chinese character shape) situated in a fibrous stroma. Notably, these bony trabeculae characteristically lack osteoblastic rimming.

Question 71

Topic: Biology, Genetics & Bone Healing

A 6-year-old boy presents with back pain and a mild kyphotic deformity. Radiographs demonstrate complete collapse of the T8 vertebral body (vertebra plana) with preservation of the adjacent disc spaces. A biopsy is performed. Which of the following markers will be strongly expressed in the lesional cells?

. Cytokeratin
. S-100 and CD1a
. CD99
. RANKL
. Vimentin only

Correct Answer & Explanation

. S-100 and CD1a

Explanation

Vertebra plana in a young child is classically caused by Eosinophilic Granuloma (Langerhans Cell Histiocytosis). The Langerhans cells characteristically stain positive for S-100 and CD1a, and contain Birbeck granules on electron microscopy.

Question 72

Topic: Biology, Genetics & Bone Healing

A 9-year-old boy presents with an isolated expansile, 'ground-glass' lytic lesion in the proximal femur causing a progressive deformity. If histological analysis is performed, what is the classic hallmark finding?

. Sheets of atypical chondrocytes with binucleation
. Woven bone trabeculae lacking osteoblastic rimming within a fibrous stroma
. Trabeculae of bone with prominent, organized osteoblastic rimming
. Spindle cells arranged in a storiform pattern with multinucleated giant cells
. Nests of epithelial cells staining positive for cytokeratin

Correct Answer & Explanation

. Woven bone trabeculae lacking osteoblastic rimming within a fibrous stroma

Explanation

The classic histological appearance of fibrous dysplasia is irregular, 'Chinese character' trabeculae of woven bone that conspicuously lack osteoblastic rimming, set in a fibrous stroma.

Question 73

Topic: Biology, Genetics & Bone Healing

A 12-year-old girl is diagnosed with polyostotic fibrous dysplasia. She presents with severe, recalcitrant bone pain in her lower extremities limiting her daily activities. Radiographs show no impending fractures. What is the most appropriate initial medical management?

. Oral corticosteroids
. Intravenous bisphosphonates
. Methotrexate
. Denosumab
. Teriparatide

Correct Answer & Explanation

. Intravenous bisphosphonates

Explanation

Intravenous bisphosphonates (such as pamidronate or zoledronic acid) are the mainstay of medical treatment for symptomatic bone pain in fibrous dysplasia, functioning by reducing osteoclastic bone turnover.

Question 74

Topic: Biology, Genetics & Bone Healing
The mother of a 4-month-old boy brings him to a physician to be evaluated for a swollen leg. The most likely diagnosis is:
. Rickets
. Osteogenesis imperfecta (OI)
. Scurvy
. Nonaccidental injury
. Caffey's disease

Correct Answer & Explanation

. Nonaccidental injury

Explanation

This radiograph shows two fractures in different stages of healing. Note the old femur fracture at the top of the field. No evidence of decreased cortical thickness, diaphyseal thinning, or bowing suggests OI. The physis of the distal femur and proximal femur show no signs of rickets. The presence of fractures rather than periosteal reaction make Caffey's disease unlikely. The fractures in scurvy are more commonly located in the physis. The diagnosis of nonaccidental injury should be made only after performing a thorough patient history and physical.

Question 75

Topic: Biology, Genetics & Bone Healing

A 15-year-old male presents with cosmetic concerns regarding his back. A lateral radiograph is shown. Which histologic abnormality at the vertebral endplate is considered the primary etiology for the characteristic findings seen in this condition?

. Abnormal enchondral ossification with disorganized cartilage matrix
. Proliferation of woven bone in the primary spongiosa
. Defective intramembranous ossification of the vertebral bodies
. Excessive osteoclastic resorption due to hyperparathyroidism
. Loss of proteoglycans primarily in the nucleus pulposus

Correct Answer & Explanation

. Abnormal enchondral ossification with disorganized cartilage matrix

Explanation

The image demonstrates Scheuermann's kyphosis with anterior wedging and Schmorl nodes. The primary histologic defect is abnormal enchondral ossification of the vertebral endplates, leading to weakened cartilage and subsequent herniation of the disc material.

Question 76

Topic: Biology, Genetics & Bone Healing

The gene that has been studied in greatest detail for application in osteoarthritis is:

. p-53
. Interleukin (IL)-13
. Tissue inhibitors of metalloproteinases-4
. IL-Receptor antagonist
. BMP-2

Correct Answer & Explanation

. IL-Receptor antagonist

Explanation

Gene therapy has been suggested as a means of delivering sustained therapeutic levels of anti-arthritic gene products to diseased joints. Local gene delivery to the synovial tissue is preferred for osteoarthritis and other conditions affecting a few joints. It is less suited to address the extra- articular components of systemic conditions, such as rheumatoid arthritis. The gene that has been studied in greatest detail encodes the human IL-1 receptor antagonist (IL-Ra).

Question 77

Topic: Biology, Genetics & Bone Healing

The gene studied for application in osteoporosis and wear-induced osteolysis is:

. Osteoprotegerin (OPG)
. Bone morphogenetic protein (BMP)
. Transforming growth factor-b1
. LMP-1
. IL-receptor antagonist

Correct Answer & Explanation

. Osteoprotegerin (OPG)

Explanation

Various cytokines and cytokine antagonists hold promise as new therapeutic agents for osteoporosis. Baltzer et al showed that intramedullary injection of Ad-IL-1Ra gene in a murine ovariectomy model strongly reduced the loss of bone mass. Using a similar model, Bolon et al studied the effect of adenovirus-mediated transfer of osteoprotegerin, which showed more bone volume with reduced osteoclast numbers in axial and appendicular bones after 4 weeks compared to sham-operated mice.

Question 78

Topic: Biology, Genetics & Bone Healing

Which of the following genes has been shown to stimulate proteoglycan synthesis for prevention of disk degeneration:

. LMP-1
. BMP-7
. Decorin
. TGF-b1
. OPG

Correct Answer & Explanation

. TGF-b1

Explanation

Intervertebral disk degeneration has been associated with a progressive decrease in proteoglycan content of nucleus pulposus. The potential application of gene therapy for prevention of disk degeneration is to increase or maintain the proteoglycan content of nucleus pulposus. Thompson et al reported that addition of TGF-b1 to canine disk tissue in culture stimulated in vitro proteoglycan synthesis.

Question 79

Topic: Biology, Genetics & Bone Healing

In designing a gene therapy construct to enhance bone formation, researchers include a specific DNA sequence located upstream of the target gene to regulate its transcription. What is this sequence called?

. Intron
. Exon
. Promoter
. Telomere
. Stop codon

Correct Answer & Explanation

. Promoter

Explanation

A promoter is a regulatory DNA sequence located upstream of a gene that binds RNA polymerase and transcription factors to initiate transcription. Tissue-specific promoters can restrict gene expression to target cells, such as osteoblasts.

Question 80

Topic: Biology, Genetics & Bone Healing

BMP-2 is delivered via an adenoviral vector to stimulate spinal fusion in an animal model. Through which intracellular signaling pathway does BMP-2 primarily exert its osteoinductive effects?

. Wnt/beta-catenin pathway
. JAK/STAT pathway
. Smad 1/5/8 pathway
. Notch signaling pathway
. Hedgehog signaling pathway

Correct Answer & Explanation

. Smad 1/5/8 pathway

Explanation

Bone morphogenetic proteins (BMPs) bind to serine/threonine kinase receptors, leading to the phosphorylation of receptor-regulated Smads (Smad 1, 5, and 8). These complex with Smad 4 to enter the nucleus and regulate transcription of osteogenic genes.

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