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1. General Principles & Basic Science MCQs

Practice Set 739 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 14761

Topic: Biology, Genetics & Bone Healing

An infant presents with severe anemia, cranial nerve palsies, and diffuse symmetric osteosclerosis on radiographs. A bone marrow transplant is being considered. What is the primary cellular defect causing this condition?

. Lack of osteoblast differentiation
. Failure of osteoclasts to resorb bone due to a defective ruffled border
. Excessive production of osteoprotegerin (OPG) by stromal cells
. Defective mineralization of hypertrophic chondrocytes
. Mutation in type I collagen synthesis pathway

Correct Answer & Explanation

. Failure of osteoclasts to resorb bone due to a defective ruffled border

Explanation

Osteopetrosis is caused by defective osteoclast function. Mutations in carbonic anhydrase II or the TCIRG1 gene prevent the formation of a functional ruffled border and the acidic microenvironment required for bone resorption.

Question 14762

Topic: Biology, Genetics & Bone Healing

An 80-year-old man complains of increasing hat size and dull, aching pain in his right thigh. Radiographs of the femur demonstrate cortical thickening and coarse trabeculae. Which of the following best describes the histologic appearance of his femur during the mixed phase of the disease?

. Woven bone with hypervascularity
. Mosaic pattern of lamellar bone with prominent cement lines
. Accumulation of unmineralized osteoid seams
. Extensive cutting cones with empty lacunae
. Palisading granulomas with multinucleated giant cells

Correct Answer & Explanation

. Mosaic pattern of lamellar bone with prominent cement lines

Explanation

Paget's disease in its mixed phase is characterized by a pathognomonic mosaic or jigsaw pattern of lamellar bone. This is due to chaotic osteoclastic resorption followed by rapid, disorganized osteoblastic bone formation leaving prominent cement lines.

Question 14763

Topic: 1. General Principles & Basic Science

A newborn presents with short stature, severe rigid clubfeet, symphalangism of the PIP joints, and "hitchhiker" thumbs. Cauliflower ears develop within the first few weeks of life. What is the underlying defect in this condition?

. Defect in type 1 collagen
. Defect in type 2 collagen
. Defect in a sulfate transporter
. Defect in fibroblast growth factor receptor 3
. Defect in cartilage oligomeric matrix protein

Correct Answer & Explanation

. Defect in a sulfate transporter

Explanation

Diastrophic dysplasia is characterized by a defect in the SLC26A2 gene, which codes for the diastrophic dysplasia sulfate transporter (DTDST). This results in undersulfated proteoglycans in the cartilage extracellular matrix.

Question 14764

Topic: Biology, Genetics & Bone Healing

A 25-year-old patient of Ashkenazi Jewish descent presents with severe hip pain. Radiographs demonstrate bilateral avascular necrosis of the femoral heads and an Erlenmeyer flask deformity of the distal femora. Laboratory tests show pancytopenia. What is the most appropriate specific medical therapy for this underlying condition?

. High-dose intravenous bisphosphonates
. Recombinant enzyme replacement therapy with imiglucerase
. Chronic phlebotomy
. Bone marrow transplant only
. Splenectomy alone

Correct Answer & Explanation

. Recombinant enzyme replacement therapy with imiglucerase

Explanation

Gaucher disease is a lysosomal storage disorder caused by a deficiency of glucocerebrosidase. Recombinant enzyme replacement therapy (e.g., imiglucerase) is the standard of care to reduce hepatosplenomegaly, improve cytopenias, and stabilize skeletal disease.

Question 14765

Topic: Biology, Genetics & Bone Healing

A 7-year-old girl is evaluated for short stature and dental anomalies, including supernumerary teeth. On physical examination, she is able to bring her shoulders together anteriorly in the midline.

A mutation in which of the following genes is responsible for her presentation?

. RUNX2 (CBFA1)
. FGFR3
. COL2A1
. SQSTM1
. SLC26A2

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the RUNX2 (CBFA1) gene. This gene is an essential transcription factor for osteoblast differentiation.

Question 14766

Topic: Biology, Genetics & Bone Healing

A 5-year-old boy presents with severe genu varum. Laboratory studies show normal serum calcium, critically low phosphorus, normal parathyroid hormone, and elevated alkaline phosphatase. Which of the following is the most appropriate definitive medical management?

. Vitamin D supplementation alone
. Oral calcium and Vitamin D
. Oral phosphorus and calcitriol
. Intravenous bisphosphonates
. Recombinant growth hormone

Correct Answer & Explanation

. Oral phosphorus and calcitriol

Explanation

The patient has X-linked hypophosphatemic rickets (PHEX mutation). Standard treatment requires combined oral phosphate and calcitriol (1,25-dihydroxyvitamin D) to correct the deficiency and prevent secondary hyperparathyroidism.

Question 14767

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with severe anemia, recurrent infections, and hepatosplenomegaly. Skeletal survey reveals generalized, profound osteosclerosis with a "bone-within-a-bone" appearance in the long bones. What is the primary cellular defect responsible for this condition?

. Failure of osteoblast differentiation
. Congenital absence of osteoclasts
. Defect in the osteoclast ruffled border
. Overactivity of osteoblasts
. Defect in osteocyte mechanotransduction

Correct Answer & Explanation

. Defect in the osteoclast ruffled border

Explanation

Osteopetrosis is caused by defective osteoclastic bone resorption, most commonly due to a failure to form the osteoclast ruffled border (often via TCIRG1 or CA2 mutations). Osteoclasts are present in normal or increased numbers but are functionally incompetent.

Question 14768

Topic: Biology, Genetics & Bone Healing
An infant presents with failure to thrive, hypotonia, and severe bowing of all extremities. Radiographs reveal profound global demineralization and widened physes. Laboratory studies demonstrate hypercalcemia and a critically low serum alkaline phosphatase. Which gene is most likely mutated?
. PHEX
. ALPL
. FGF23
. COL1A1
. ENPP1

Correct Answer & Explanation

. ALPL

Explanation

Hypophosphatasia is a severe metabolic bone disease caused by a mutation in the ALPL gene. This leads to deficient tissue-nonspecific alkaline phosphatase (TNSALP) activity, impairing skeletal mineralization and mimicking rickets radiographically.

Question 14769

Topic: Biology, Genetics & Bone Healing

A 7-year-old girl is evaluated for short stature and an unusual shoulder appearance. Clinical examination reveals hypermobility of the shoulders, allowing them to touch in the midline.

Which of the following genes is mutated in this patient's condition?

. COL1A1
. FGFR3
. RUNX2 (CBFA1)
. COMP
. SLC26A2

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the RUNX2 (CBFA1) transcription factor. It is characterized by hypoplastic or absent clavicles and delayed closure of cranial sutures.

Question 14770

Topic: Biology, Genetics & Bone Healing

A 65-year-old man presents with progressive bowing of his right tibia, increasing thigh pain, and increasing hat size. Radiographs reveal cortical thickening and coarsened trabeculae of the tibia. Which of the following best describes the initial pathogenesis of this disease?

. Abnormal mineralization of osteoid
. Intense focal osteoclastic resorption of bone
. Defective osteoclast ruffled border
. Excessive uncoupled osteoblastic bone formation
. Failure of endochondral ossification

Correct Answer & Explanation

. Intense focal osteoclastic resorption of bone

Explanation

Paget's disease begins with an initial osteolytic phase driven by intense focal osteoclastic resorption. This is followed by a mixed osteoblastic-osteoclastic phase, and finally a sclerotic phase.

Question 14771

Topic: 1. General Principles & Basic Science

A newborn presents with micromelia, bilateral clubfeet, hitchhiker thumbs, and swelling of the auricles (cauliflower ears). A defect in which of the following mechanisms is responsible for this condition?

. Sulfate transport
. Fibroblast growth factor receptor
. Cartilage oligomeric matrix protein
. Type II collagen synthesis
. Carbonic anhydrase function

Correct Answer & Explanation

. Sulfate transport

Explanation

Diastrophic dysplasia is caused by a mutation in the SLC26A2 (DTDST) gene, leading to defective sulfate transport. This impairs proteoglycan sulfation in cartilage matrix.

Question 14772

Topic: Biology, Genetics & Bone Healing

A 3-year-old boy presents with progressive bowing of the legs and short stature. Laboratory evaluation shows low serum phosphate, normal calcium, normal PTH, and elevated alkaline phosphatase. Genetic testing reveals a mutation in the PHEX gene. Which of the following is the primary pathophysiologic mechanism?

. Decreased renal tubular reabsorption of phosphate due to elevated FGF23
. Decreased intestinal absorption of calcium due to low 1,25-dihydroxyvitamin D
. Excessive renal loss of calcium leading to secondary hyperparathyroidism
. Mutation in tissue-nonspecific alkaline phosphatase preventing mineralization
. Autoimmune destruction of parathyroid glands

Correct Answer & Explanation

. Decreased renal tubular reabsorption of phosphate due to elevated FGF23

Explanation

In X-linked hypophosphatemic rickets, a PHEX mutation leads to overproduction of FGF23. FGF23 decreases renal phosphate reabsorption, causing hypophosphatemia and rickets.

Question 14773

Topic: Biology, Genetics & Bone Healing

A 10-month-old infant presents with irritability, bleeding gums, and painful swollen lower extremities. Radiographs of the knees show a dense zone of provisional calcification, a radiolucent band beneath it, and a marginal spur (Pelkan spur). Which of the following steps in collagen synthesis is primarily impaired?

. Cleavage of procollagen N- and C-terminals
. Hydroxylation of proline and lysine residues
. Assembly of three alpha chains into a triple helix
. Glycosylation of hydroxylysine residues
. Cross-linking of tropocollagen molecules by lysyl oxidase

Correct Answer & Explanation

. Hydroxylation of proline and lysine residues

Explanation

The clinical presentation describes scurvy (Vitamin C deficiency). Vitamin C is an essential cofactor for prolyl and lysyl hydroxylase, and its absence prevents proper hydroxylation of proline and lysine.

Question 14774

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with short trunk dwarfism, a barrel chest, and coxa vara. Radiographs reveal flattening of the vertebral bodies and delayed ossification of the femoral head and neck epiphyses. An abnormality in which of the following proteins is the underlying cause?

. Type I collagen
. Type II collagen
. Type X collagen
. COMP
. Aggrecan

Correct Answer & Explanation

. Type II collagen

Explanation

Spondyloepiphyseal dysplasia (SED) affects both the spine and epiphyses. It is caused by a mutation in the COL2A1 gene, resulting in defective Type II collagen.

Question 14775

Topic: Biology, Genetics & Bone Healing

A 6-year-old girl with osteogenesis imperfecta is treated with intravenous pamidronate.

What is the primary mechanism of action of this medication in this patient?

. Stimulation of osteoblast proliferation
. Induction of osteoclast apoptosis and inhibition of bone resorption
. Enhancement of Type I collagen cross-linking
. Direct stimulation of renal calcium reabsorption
. Inhibition of parathyroid hormone secretion

Correct Answer & Explanation

. Induction of osteoclast apoptosis and inhibition of bone resorption

Explanation

Bisphosphonates like pamidronate are internalized by osteoclasts and induce apoptosis by inhibiting the mevalonate pathway. This reduces bone resorption and increases bone mass in patients with OI.

Question 14776

Topic: Biology, Genetics & Bone Healing

An 18-month-old child presents with enlarged wrists, bowing of the legs, and frontal bossing. Laboratory studies demonstrate low serum 25-hydroxyvitamin D, low-normal calcium, low phosphorus, and significantly elevated parathyroid hormone. Which of the following is the most likely diagnosis?

. Nutritional rickets
. X-linked hypophosphatemic rickets
. Renal osteodystrophy
. Hypophosphatasia
. Vitamin D-dependent rickets type II

Correct Answer & Explanation

. Nutritional rickets

Explanation

Nutritional rickets is characterized by vitamin D deficiency leading to decreased calcium and phosphate absorption. This causes secondary hyperparathyroidism, which normalizes calcium at the expense of severe hypophosphatemia and bone demineralization.

Question 14777

Topic: Biology, Genetics & Bone Healing

A 55-year-old woman presents with a pathologic fracture of her proximal humerus. Radiographs show a well-defined lytic lesion. Laboratory values reveal hypercalcemia, hypophosphatemia, and markedly elevated alkaline phosphatase. Which of the following describes the histological appearance of this bone lesion?

. Sheets of atypical plasma cells with eccentric nuclei
. Woven bone trabeculae in a fibrous stroma without osteoblastic rimming
. Increased numbers of osteoclasts and giant cells in a hemorrhagic fibrovascular stroma
. Malignant spindle cells producing disorganized osteoid
. Nests of uniform round cells with fried egg appearance

Correct Answer & Explanation

. Increased numbers of osteoclasts and giant cells in a hemorrhagic fibrovascular stroma

Explanation

The clinical scenario is classic for primary hyperparathyroidism leading to a brown tumor (osteitis fibrosa cystica). Histologically, brown tumors consist of numerous multinucleated giant cells and osteoclasts in a highly vascular, hemorrhagic stroma.

Question 14778

Topic: Biology, Genetics & Bone Healing

An 8-year-old boy presents with the ability to bring his shoulders together in the midline. Radiographs reveal hypoplastic clavicles as shown.

Which of the following genes is mutated in this condition?

. COL1A1
. RUNX2
. FGFR3
. COMP
. SLC26A2

Correct Answer & Explanation

. RUNX2

Explanation

Cleidocranial dysplasia is caused by a mutation in the RUNX2 (CBFA1) gene, which is essential for osteoblast differentiation. It is characterized by delayed fontanelle closure, hypoplastic clavicles, and supernumerary teeth.

Question 14779

Topic: Biology, Genetics & Bone Healing

A 12-year-old boy with a history of multiple fractures presents with progressive loss of forearm rotation. Radiographs demonstrate calcification of the interosseous membrane and a dislocated radial head. Which of the following is characteristic of his specific condition?

. COL1A1 mutation
. Hypertrophic callus formation
. Blue sclerae
. Dentinogenesis imperfecta
. Severe wormian bones

Correct Answer & Explanation

. Hypertrophic callus formation

Explanation

This presentation is classic for Osteogenesis Imperfecta Type V, caused by an IFITM5 mutation (not COL1A1/COL1A2). It is uniquely associated with hyperplastic callus formation and calcification of the forearm interosseous membrane.

Question 14780

Topic: Biology, Genetics & Bone Healing

A pediatric patient with osteogenesis imperfecta is started on intravenous pamidronate. Which of the following best describes the cellular mechanism of action of this medication?

. Stimulates osteoblast differentiation
. Inhibits farnesyl pyrophosphate synthase in osteoclasts
. Agonizes the Wnt/beta-catenin pathway
. Blocks the RANKL receptor
. Inhibits sclerostin

Correct Answer & Explanation

. Inhibits farnesyl pyrophosphate synthase in osteoclasts

Explanation

Nitrogen-containing bisphosphonates like pamidronate inhibit farnesyl pyrophosphate synthase in the mevalonate pathway. This leads to osteoclast apoptosis, thereby reducing bone resorption and increasing bone density.

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