What is the primary cellular effect of chronic glucocorticoid use on bone that drives osteoporosis?

• A. Decreased osteoblast activity
• B. Increased osteoclast formation
• C. Increased intestinal calcium absorption
• D. Increased bone mineral density

Answer: (A)

Chronic glucocorticoid exposure primarily suppresses bone formation by osteoblasts. Glucocorticoids inhibit the differentiation of bone-forming cells from precursor cells, promote osteoblast and osteocyte apoptosis, and decrease production of collagen and other factors needed to build new bone. This lowers the rate of bone formation, causing bone mass to fall over time and leading to osteoporosis.

While glucocorticoids can influence osteoclasts indirectly (through changes in signaling molecules like RANKL and OPG), the dominant cellular effect that drives this condition is the marked reduction in osteoblast activity and survival. Increased intestinal calcium absorption does not occur with glucocorticoids, and increased bone mineral density would contradict the observed outcome.