A 72-year-old woman comes to the office for a routine health maintenance visit. She feels well and has no specific complaints. Her medical history is significant for rheumatoid arthritis, for which she has taken 10 mg of prednisone daily for many years. She has a 40-pack-year smoking history and drinks two glasses of wine daily. Her mother suffered a hip fracture at age 75. On physical examination, her height is 162 cm (5'4"), which is 5 cm (2 inches) less than her recorded height five years ago. There is a mild thoracic kyphosis. A dual-energy X-ray absorptiometry (DEXA) scan shows a T-score of -2.8 at the lumbar spine and -2.6 at the femoral neck. Laboratory studies, including serum calcium, phosphate, and parathyroid hormone (PTH) levels, are within normal limits.
Which of the following is the most likely primary mechanism for this patient's increased bone fragility?
The correct answer is:
C) Excessive bone resorption by osteoclasts exceeding bone formation by osteoblasts
The patient has osteoporosis, characterized by a T-score ≤ -2.5 on DEXA scan. The primary pathophysiology of osteoporosis, especially in postmenopausal and age-related cases, is an imbalance in the bone remodeling cycle where bone resorption by osteoclasts exceeds bone formation by osteoblasts. This leads to a decrease in total bone mass and microarchitectural deterioration of bone tissue, though the mineral-to-protein ratio remains normal. This patient has multiple risk factors, including advanced age, postmenopausal status, smoking, and chronic corticosteroid use. The loss of height and thoracic kyphosis ("dowager's hump") suggest prior asymptomatic vertebral compression fractures.
Answer choice A: Decreased osteoblast activity and increased osteoclast apoptosis, is incorrect. This is actually the opposite of what occurs in osteoporosis. While corticosteroids do decrease osteoblast activity, they typically decrease osteoclast apoptosis, leading to a longer osteoclast lifespan, and increase osteoclast recruitment, thereby accelerating bone loss.
Answer choice B: Defective mineralization of osteoid, is incorrect. This describes osteomalacia, which is most commonly due to vitamin D deficiency. In osteomalacia, the bone mass may be normal or low, but the bone that is present is inadequately mineralized, leading to soft bones. Laboratory findings usually show low vitamin D, low calcium, and elevated PTH, unlike the normal labs seen in primary osteoporosis.
Answer choice D: Impaired collagen cross-linking, is incorrect. This is a feature of osteogenesis imperfecta, a genetic disorder caused by mutations in the genes coding for Type I collagen. While it does lead to bone fragility, it typically presents in childhood with multiple fractures and other systemic signs like blue sclerae.
Answer choice E: Increased PTH-mediated bone turnover, is incorrect. This describes primary hyperparathyroidism (osteitis fibrosa cystica). While chronic elevations in PTH do cause bone resorption (classically "subperiosteal thinning" and "salt-and-pepper" skull), this patient’s normal PTH level makes this diagnosis unlikely as the primary cause of her T-score.
Key Learning Point
Osteoporosis is characterized by a decrease in bone mass with normal mineralization, resulting from a remodeling imbalance where osteoclast-mediated bone resorption outpaces osteoblast-mediated bone formation. Risk factors include low estrogen, chronic corticosteroid use, smoking, and advanced age.
