1. General Principles & Basic Science MCQs

An infant presents with failure to thrive, dense bones on radiography, cerebral calcifications, and renal tubular acidosis.

This specific constellation of findings is most characteristic of a deficiency in which of the following enzymes?

During the initial phase of Paget's disease, osteoclasts demonstrate intense resorptive activity. On a radiograph of the tibia, this early stage is classically represented by which of the following findings?

Trichorhinophalangeal syndrome (TRPS) type 1, which features cone-shaped epiphyses and early hip degeneration, is inherited in an autosomal dominant pattern. The responsible TRPS1 gene is located on which chromosome?

A 72-year-old man with Paget's disease of the pelvis and proximal femur undergoes a total hip arthroplasty for severe osteoarthritis. Which of the following complications is significantly increased in this patient compared to a non-pagetic patient?

A biopsy of an expanded, bowed tibia in an elderly patient is shown.

The prominent, haphazardly arranged cement lines forming a 'mosaic pattern' are most characteristic of which phase of this disease?

A 6-month-old infant presents with failure to thrive, hepatosplenomegaly, and severe pancytopenia. Radiographs reveal diffuse osteosclerosis. What is the only potential curative treatment for this patient's underlying condition?

A 4-month-old infant presents with hepatosplenomegaly, failure to thrive, and vision loss. Radiographs reveal diffuse, uniform osteosclerosis of all bones. Genetic testing reveals a mutation in the TCIRG1 gene. What is the primary cellular mechanism responsible for this patient's condition?

A 68-year-old man with increasing head size and deep bone pain in his right thigh undergoes laboratory testing. Which of the following serum profiles is most consistent with the active mixed phase of his likely diagnosis?

A 65-year-old woman is diagnosed with symptomatic Paget's disease affecting her pelvis and lumbar spine. She is prescribed first-line pharmacological therapy. What is the primary mechanism of action of the most appropriate medication?

A bone biopsy is obtained from a 15-year-old male with a history of recurrent fractures and dense bones on radiography. Histologic examination reveals persistence of primary spongiosa with calcified cartilage cores within mature trabecular bone. Which diagnosis is most consistent with these findings?

A 70-year-old man undergoes a biopsy of an expanding lytic and sclerotic lesion in his tibia. The histology shows a chaotic, mosaic pattern of lamellar bone with prominent, irregular cement lines. Which gene mutation is most strongly associated with this condition?

A 60-year-old male presents with dull aching pain in his lower leg. A radiograph of his tibia is shown.

The image demonstrates a sharply demarcated, V-shaped radiolucency advancing down the diaphysis. What does this "blade of grass" sign represent?

A 75-year-old man with polyostotic Paget's disease presents with progressive dyspnea on exertion, fatigue, and lower extremity edema. Echocardiography shows an ejection fraction of 65% with elevated cardiac output. What is the primary cause of his cardiac symptoms?

What is the only definitive curative treatment for the malignant infantile (autosomal recessive) form of osteopetrosis?

A family is evaluated for a condition characterized by short stature, sparse scalp hair, long flat philtrum, and joint pain. Clinical imaging shows cone-shaped epiphyses.

Genetic testing reveals a mutation in the TRPS1 gene. What is the genetic inheritance pattern of this syndrome?

A 68-year-old man requires a total hip arthroplasty for severe secondary osteoarthritis due to Paget's disease of the right hemipelvis and proximal femur. His preoperative alkaline phosphatase is 4 times the upper limit of normal. What is the most appropriate preoperative medical management?

A 14-year-old girl is diagnosed with a rare variant of osteopetrosis. In addition to dense, brittle bones, she exhibits cerebral calcifications and metabolic acidosis. A mutation in which of the following enzymes is most likely responsible?

A 4-year-old child presents with frequent fractures, developmental delay, and metabolic acidosis. Radiographs reveal diffuse, uniform osteosclerosis. Genetic testing confirms a mutation in the CA2 gene. Which of the following is the underlying pathophysiological mechanism of this specific subtype of osteopetrosis?