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Biology, Genetics & Bone Healing MCQs

Practice Set 205 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 4081

Topic: Biology, Genetics & Bone Healing

A 65-year-old male presents with increasing thigh pain. Radiographs reveal cortical thickening, coarsened trabeculae, and a radiolucent V-shaped lesion in the femoral diaphysis. What is the primary cellular defect in this disease?

. Defective osteoblast mineralization
. Defective osteoclast recruitment and overactivity
. Mutation in type 1 collagen
. Deficiency of tissue nonspecific alkaline phosphatase
. Impaired renal hydroxylation of 25-hydroxyvitamin D

Correct Answer & Explanation

. Defective osteoclast recruitment and overactivity

Explanation

Paget's disease is driven by abnormal, highly active osteoclasts (often with paramyxovirus-like inclusion bodies), leading to a secondary robust but disorganized osteoblastic response. The classic 'blade of grass' or V-shaped lytic lesion represents the advancing osteolytic front.

Question 4082

Topic: Biology, Genetics & Bone Healing

A 5-year-old boy presents with profound genu varum and short stature. Laboratory tests show low serum phosphate, normal serum calcium, and elevated FGF-23 levels. What is the standard medical treatment?

. Intravenous bisphosphonates
. High-dose Vitamin D alone
. Oral phosphate and calcitriol
. Recombinant human growth hormone
. Cinacalcet

Correct Answer & Explanation

. Oral phosphate and calcitriol

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX mutation leading to elevated FGF-23, which causes renal phosphate wasting and decreased calcitriol synthesis. Treatment requires both oral phosphate supplementation and calcitriol (1,25-dihydroxyvitamin D) to heal rickets and prevent secondary hyperparathyroidism.

Question 4083

Topic: Biology, Genetics & Bone Healing

A 3-year-old child presents with a femoral fracture after a minor fall. Radiographs show a "bone-within-bone" appearance and generalized sclerosis. Laboratory findings reveal mild anemia and thrombocytopenia. What is the most likely genetic defect?

. COL1A1 mutation
. FGFR3 mutation
. TCIRG1 mutation
. RUNX2 mutation
. COMP mutation

Correct Answer & Explanation

. TCIRG1 mutation

Explanation

Malignant infantile osteopetrosis is commonly caused by mutations in TCIRG1, leading to an inability of osteoclasts to acidify Howship's lacunae. This results in failed bone resorption, densely sclerotic but brittle bones, and obliteration of the medullary cavity causing pancytopenia.

Question 4084

Topic: Biology, Genetics & Bone Healing

A 6-year-old girl with multiple prior fractures, blue sclerae, and dentinogenesis imperfecta is scheduled for rodding of bilateral femurs. Which of the following defects is the primary cause of her underlying condition?

. Defective osteoclast chloride channels
. Defective synthesis of Type II collagen
. Quantitative or qualitative defect in Type I collagen
. Impaired endochondral ossification
. Defective mineralization of osteoid

Correct Answer & Explanation

. Quantitative or qualitative defect in Type I collagen

Explanation

Osteogenesis imperfecta is predominantly an autosomal dominant disorder caused by mutations in the COL1A1 or COL1A2 genes, leading to qualitative or quantitative defects in Type I collagen. This results in brittle bones, blue sclerae, and dentinogenesis imperfecta.

Question 4085

Topic: Biology, Genetics & Bone Healing

A 12-year-old boy presents with a prominent forehead, delayed tooth eruption, and an unusually wide range of shoulder motion, easily approximating his shoulders anteriorly. A mutation in which transcription factor is responsible for this condition?

. SOX9
. RUNX2 (CBFA1)
. COMP
. FGFR3
. GLI3

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the RUNX2 (CBFA1) gene, which is essential for osteoblast differentiation. Key features include hypoplastic or absent clavicles, delayed closure of cranial sutures, and supernumerary teeth.

Question 4086

Topic: Biology, Genetics & Bone Healing
A 10-month-old infant exclusively fed boiled cow's milk presents with irritability, bleeding gums, and a pseudoparalysis of the lower extremities. Radiographs show a dense zone of provisional calcification and a lucent metaphyseal band. This condition is caused by a deficiency that directly impairs which biochemical process?
. Cross-linking of elastin
. Hydroxylation of proline and lysine residues in collagen
. Cleavage of procollagen C-terminals
. Mineralization of osteoid matrix
. Osteoclast attachment to the bone surface

Correct Answer & Explanation

. Hydroxylation of proline and lysine residues in collagen

Explanation

Scurvy is caused by Vitamin C deficiency, leading to impaired hydroxylation of proline and lysine residues, which is necessary for stable collagen triple helix formation. Radiographic hallmarks include the white line of Frankel (dense calcification) and the Trümmerfeld zone (lucent band).

Question 4087

Topic: Biology, Genetics & Bone Healing

A 65-year-old man presents with progressive bowing of his right femur and increasing hat size. Laboratory tests reveal an isolated, significantly elevated serum alkaline phosphatase. Histological examination of the affected bone is most likely to show:

. Defective osteoid mineralization with widened osteoid seams
. A mosaic pattern of lamellar bone with prominent cement lines
. Thin cortical trabeculae with normal mineralization ratios
. Multinucleated giant cells in a background of spindle cells
. Subperiosteal bone resorption with dissecting osteitis

Correct Answer & Explanation

. A mosaic pattern of lamellar bone with prominent cement lines

Explanation

The patient's presentation and isolated elevated alkaline phosphatase are classic for Paget's disease of bone. Histology demonstrates a characteristic mosaic pattern of lamellar bone with prominent, haphazard cement lines due to unregulated cycles of bone resorption and formation.

Question 4088

Topic: Biology, Genetics & Bone Healing

A 55-year-old patient with end-stage renal disease presents with diffuse bone pain. Radiographs demonstrate subperiosteal resorption of the phalanges and a "rugger jersey" spine. The patient's condition is primarily driven by which of the following initial metabolic derangements?

. Decreased serum phosphate and elevated active vitamin D
. Elevated serum phosphate and decreased active vitamin D
. Elevated serum calcium and decreased active vitamin D
. Decreased serum PTH and elevated serum calcium
. Autoantibody formation against calcium-sensing receptors

Correct Answer & Explanation

. Elevated serum phosphate and decreased active vitamin D

Explanation

Renal osteodystrophy is driven by failing kidneys that retain phosphate and fail to convert 25(OH)D to active 1,25(OH)2D. The resulting hyperphosphatemia and hypocalcemia stimulate secondary hyperparathyroidism, leading to severe bone resorption.

Question 4089

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy with recurrent fractures, blue sclerae, and dentinogenesis imperfecta is treated with intravenous pamidronate. The primary mechanism of action of this medication in this patient's disease is:

. Stimulation of osteoblastic collagen synthesis
. Inhibition of farnesyl pyrophosphate synthase in osteoclasts
. Binding to RANKL to prevent osteoclast activation
. Direct enhancement of intestinal calcium absorption
. Substitution of defective type 1 collagen fibrils

Correct Answer & Explanation

. Inhibition of farnesyl pyrophosphate synthase in osteoclasts

Explanation

Pamidronate is a nitrogen-containing bisphosphonate used to reduce fracture burden in Osteogenesis Imperfecta. It works by inhibiting farnesyl pyrophosphate synthase, which disrupts osteoclast function and promotes osteoclast apoptosis.

Question 4090

Topic: Biology, Genetics & Bone Healing

A 3-year-old boy presents with progressive varus bowing of the lower extremities. Labs show normal serum calcium, low serum phosphate, normal parathyroid hormone, and normal 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D is inappropriately normal-low. Which of the following is the most likely mediator of this condition?

. Deficient dietary calcium intake
. Excess circulating fibroblast growth factor 23 (FGF23)
. Autoimmune destruction of parathyroid glands
. Impaired 1-alpha-hydroxylase activity in the kidney
. Defective intestinal vitamin D receptors

Correct Answer & Explanation

. Excess circulating fibroblast growth factor 23 (FGF23)

Explanation

These findings are classic for X-linked hypophosphatemic rickets, caused by a PHEX gene mutation. This results in excess FGF23, which profoundly inhibits renal phosphate reabsorption and 1-alpha-hydroxylase activity, leading to isolated hypophosphatemia.

Question 4091

Topic: Biology, Genetics & Bone Healing

A 12-year-old boy presents to the orthopedic clinic with a remarkably broad forehead and the ability to approximate his shoulders in the anterior midline. Radiographs reveal delayed ossification of the cranial sutures and complete absence of the clavicles. The mutated gene responsible for this condition is a critical transcription factor for:

. Chondrocyte hypertrophy
. Osteoblast differentiation
. Osteoclast activation
. Type II collagen synthesis
. Sulfation of proteoglycans

Correct Answer & Explanation

. Osteoblast differentiation

Explanation

Cleidocranial dysplasia is caused by a mutation in RUNX2 (CBFA1). RUNX2 is a master transcription factor essential for the differentiation of mesenchymal stem cells into functional osteoblasts.

Question 4092

Topic: Biology, Genetics & Bone Healing

A young child presents with frequent fractures, hepatosplenomegaly, and pancytopenia. Radiographs reveal generalized, densely sclerotic bones with an "Erlenmeyer flask" deformity of the distal femora. A defect in which of the following enzymes is classically associated with the autosomal recessive form of this disease?

. Alkaline phosphatase
. Cathepsin K
. Tartrate-resistant acid phosphatase
. Carbonic anhydrase II
. Lysyl hydroxylase

Correct Answer & Explanation

. Carbonic anhydrase II

Explanation

Malignant infantile osteopetrosis is an autosomal recessive disorder characterized by non-functional osteoclasts. It is frequently caused by mutations affecting carbonic anhydrase II (or the TCIRG1 gene), preventing osteoclasts from generating the acidic environment necessary for bone resorption.

Question 4093

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with severe genu varum and short stature. Lab evaluation reveals normal serum calcium, low serum phosphate, and elevated alkaline phosphatase. Genetic testing shows a PHEX mutation. Which medical therapy is indicated?

. Oral calcium and Vitamin D3
. Bisphosphonates
. Calcitriol and oral phosphate
. Cinacalcet
. Recombinant PTH

Correct Answer & Explanation

. Calcitriol and oral phosphate

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX mutation leading to elevated FGF23, renal phosphate wasting, and impaired vitamin D activation. Standard treatment includes active vitamin D (calcitriol) and oral phosphate supplementation.

Question 4094

Topic: Biology, Genetics & Bone Healing

A neonate presents with multiple fractures, blue sclerae, and dentinogenesis imperfecta. A defect in which of the following is the primary cause of this condition?

. Type II collagen
. Type I collagen
. Fibroblast growth factor receptor 3
. Runx2/Cbfa1 transcription factor
. Cartilage oligomeric matrix protein (COMP)

Correct Answer & Explanation

. Type I collagen

Explanation

Osteogenesis imperfecta is primarily caused by mutations in the COL1A1 or COL1A2 genes, which lead to qualitative or quantitative defects in Type I collagen. This results in bone fragility, blue sclerae, and dentinogenesis imperfecta.

Question 4095

Topic: Biology, Genetics & Bone Healing

A 9-year-old patient exhibits delayed closure of cranial sutures, absent clavicles, and delayed eruption of secondary teeth. The gene responsible for this condition plays a crucial role in which cellular process?

. Osteoclast differentiation
. Osteoblast differentiation
. Chondrocyte hypertrophy
. Collagen cross-linking
. Mineralization of osteoid

Correct Answer & Explanation

. Osteoblast differentiation

Explanation

Cleidocranial dysplasia is caused by a mutation in the RUNX2 (CBFA1) gene, which is an essential transcription factor for osteoblast differentiation. This defect severely impacts membranous bone formation, leading to absent clavicles and delayed cranial suture closure.

Question 4096

Topic: Biology, Genetics & Bone Healing

A 55-year-old female with a history of Roux-en-Y gastric bypass presents with diffuse bone pain and muscle weakness. Radiographs reveal bilateral transverse radiolucent bands in the medial femoral necks. Lab tests show low vitamin D and elevated PTH. What is the radiologic finding called?

. Brown tumors
. Looser zones
. Cotton wool appearance
. Rugger jersey spine
. Erlenmeyer flask deformity

Correct Answer & Explanation

. Looser zones

Explanation

Looser zones (pseudofractures) are transverse bands of non-mineralized osteoid and are the radiographic hallmark of osteomalacia. In this patient, osteomalacia is secondary to vitamin D malabsorption from her previous gastric bypass.

Question 4097

Topic: Biology, Genetics & Bone Healing

A 70-year-old female with severe postmenopausal osteoporosis has sustained multiple vertebral compression fractures despite bisphosphonate therapy. Her physician recommends initiating teriparatide. Which of the following is an absolute contraindication to this medication?

. Prior history of deep vein thrombosis
. History of radiation therapy to the skeleton
. Gastroesophageal reflux disease
. Chronic kidney disease stage 3
. History of a hip fracture

Correct Answer & Explanation

. History of radiation therapy to the skeleton

Explanation

Teriparatide (recombinant PTH) is an anabolic agent used for severe osteoporosis. It is contraindicated in patients with a history of skeletal radiation therapy, Paget's disease, or unexplained elevated alkaline phosphatase due to an increased theoretical risk of osteosarcoma.

Question 4098

Topic: Biology, Genetics & Bone Healing

A 45-year-old patient on long-term hemodialysis develops severe bone pain and is diagnosed with adynamic bone disease. Which laboratory profile is most consistent with this diagnosis?

. Low calcium, low phosphorus, highly elevated PTH
. High calcium, low phosphorus, low PTH
. Normal to high calcium, normal phosphorus, markedly suppressed PTH
. Low calcium, high phosphorus, elevated alkaline phosphatase
. Low vitamin D, high PTH, low alkaline phosphatase

Correct Answer & Explanation

. Normal to high calcium, normal phosphorus, markedly suppressed PTH

Explanation

Adynamic bone disease is a form of renal osteodystrophy characterized by profoundly decreased bone turnover. It is typically associated with iatrogenic over-suppression of the parathyroid gland, resulting in markedly low PTH levels and normal to high serum calcium.

Question 4099

Topic: Biology, Genetics & Bone Healing

A 5-year-old girl presents with progressive lower extremity bowing. Labs show normal serum calcium, significantly low serum phosphate, and elevated alkaline phosphatase. Genetic testing reveals a PHEX gene mutation. What is the most targeted contemporary medical treatment for this condition?

. High-dose Vitamin D (Cholecalciferol)
. Burosumab (Anti-FGF23 monoclonal antibody)
. Intravenous Bisphosphonates
. Recombinant human parathyroid hormone
. Cinacalcet

Correct Answer & Explanation

. Burosumab (Anti-FGF23 monoclonal antibody)

Explanation

X-linked hypophosphatemic rickets (XLH) is caused by a PHEX mutation leading to excessive FGF23 production, which wastes phosphate in the kidneys. Burosumab is an anti-FGF23 monoclonal antibody that directly addresses the underlying pathophysiology and is now the definitive treatment.

Question 4100

Topic: Biology, Genetics & Bone Healing

A 9-year-old boy presents to the orthopedic clinic. Examination reveals delayed closure of cranial fontanelles, the ability to appose his shoulders anteriorly at the midline, and a wide pubic symphysis on radiographs. This condition is associated with a mutation in which of the following genes?

. RUNX2 (CBFA1)
. FGFR3
. COL1A1
. COMP
. SOX9

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the RUNX2 (CBFA1) transcription factor, which is essential for osteoblast differentiation. It is characterized by absent/hypoplastic clavicles, delayed cranial suture closure, and supernumerary teeth.

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