1. General Principles & Basic Science MCQs

A 65-year-old man presents with back pain, fatigue, and hypercalcemia. Radiographs demonstrate multiple 'punched-out' lytic lesions in his skull and pelvis. A technetium-99m bone scan is reportedly 'cold' in the areas of these lesions. What is the primary reason for the lack of uptake on the bone scan?

A 72-year-old man with increasing hat size, hearing loss, and bowing of his tibias presents for evaluation. Radiographs show thickened cortices and a 'cotton wool' appearance of the skull. A bone biopsy in the sclerotic phase would most likely reveal which of the following histological features?

A 15-year-old boy presents with knee pain. Radiographs demonstrate a 2 cm lytic lesion strictly confined to the proximal tibial epiphysis with a thin sclerotic rim. Histological examination shows mononuclear cells with grooved nuclei and areas of 'chicken-wire' calcification. Which of the following is the most appropriate treatment?

A 9-year-old boy falls and sustains a pathologic fracture of his proximal humerus. Radiographs reveal a centrally located, completely lytic lesion in the metaphysis that abuts the physis. A bone fragment is seen resting at the dependent portion of the cyst. Which of the following statements about the cyst fluid is most accurate?

A 30-year-old Ashkenazi Jewish man presents with severe, acute left thigh pain and fever, initially mimicking osteomyelitis. Radiographs of the femur show an 'Erlenmeyer flask' deformity of the distal femur with scattered lytic and sclerotic areas. He also has hepatosplenomegaly. Deficiency of which of the following enzymes is responsible for his skeletal manifestations?

A 72-year-old man undergoes a biopsy of a densely sclerotic lesion in his L4 vertebral body. Pathology reveals irregular bone trabeculae lined by uniform atypical cells with prominent nucleoli forming back-to-back glands. Immunohistochemistry is strongly positive for PSA. Which of the following factors is primarily responsible for the osteosclerotic (osteoblastic) appearance of these metastases?

A 15-year-old male with a history of multiple soft-tissue hemangiomas presents with a newly symptomatic, expansile cartilaginous lesion in his right humerus. He is diagnosed with Maffucci syndrome. The pathogenesis of his skeletal and vascular lesions is most strongly associated with somatic mosaic mutations in which of the following genes?

Denosumab is an effective systemic treatment for surgically unsalvageable or metastatic Giant Cell Tumor of Bone (GCTB). It works by binding to RANKL. In the pathophysiology of GCTB, which cellular population is the primary source of RANKL expression?

Multiple myeloma bone disease is characterized by purely osteolytic lesions with virtually no reactive new bone formation, leading to a negative ('cold') bone scan in many cases. The profound suppression of osteoblast function in these lesions is primarily mediated by myeloma cell secretion of which molecule?

A 60-year-old man presents with an increasing hat size and bowing of his tibiae. Radiographs show thickened, disorganized trabeculae and cortical thickening ('cotton wool' appearance). A genetic evaluation is performed due to a strong family history. An activating mutation in which of the following genes is most commonly associated with the familial form of this disease?

A 65-year-old man presents with severe back pain and fatigue. Laboratory studies reveal hypercalcemia, anemia, and an elevated serum creatinine. Radiographs show multiple punched-out lytic lesions in his skull and spine. A technetium-99m bone scan is notable for a lack of uptake in the corresponding lytic areas. What is the primary mechanism of bone destruction in this condition?

An 8-year-old child presents with multiple painless bony masses near the joints of the knees, ankles, and shoulders. Radiographs reveal multiple broad-based, cartilage-capped bony outgrowths continuous with the medullary cavity of the parent bone. The pathogenesis of this condition most directly involves abnormal function in which signaling pathway component?

A 6-year-old child sustains an extension-type supracondylar humerus fracture with posterolateral displacement. Which of the following neurologic structures is at greatest risk of injury?

A 4-year-old boy presents with right hip pain, a limp, and refusal to bear weight. His temperature is 38.6°C (101.5°F), WBC count is 13.5 x 10^9/L, and ESR is 45 mm/hr. Based on the modified Kocher criteria, what is the approximate probability that this child has septic arthritis rather than transient synovitis?

An 8-year-old girl presents with a painless snapping and popping sensation in her lateral right knee, particularly during extension. MRI confirms a complete (Watanabe Type I) discoid lateral meniscus with no evidence of tearing or instability. What is the most appropriate management?

A 2-year-old boy presents with anterolateral bowing of the tibia. Radiographs show a narrowing of the medullary canal at the apex of the deformity. A diagnosis of congenital pseudarthrosis of the tibia (CPT) is suspected.

Which of the following interventions during surgical reconstruction is most critical for achieving long-term union?

A 5-year-old girl with recurrent long bone fractures and blue sclerae is diagnosed with Osteogenesis Imperfecta (OI) type I. She is started on intravenous pamidronate therapy.

What is the primary mechanism of action of this pharmacological treatment?

A 4-year-old boy presents with progressive bowing of his lower extremities and short stature. Laboratory evaluation reveals hypophosphatemia, normal serum calcium, normal parathyroid hormone (PTH), and elevated alkaline phosphatase.

What is the underlying genetic defect in the most likely diagnosis?

A 4-year-old child with a history of multiple low-energy fractures, blue sclerae, and dentinogenesis imperfecta is started on pamidronate therapy. What is the primary cellular mechanism of action of this pharmacological agent?