Which mechanism contributes most directly to the rapid trabecular bone loss seen within months of starting high-dose oral corticosteroids?

• A Enhanced conversion of 25-hydroxyvitamin D to its active form
• B Increased renal tubular reabsorption of calcium
• C Stimulation of parathyroid gland hyperplasia
• D Direct suppression of osteoblast differentiation and activity ✓

Explanation

Glucocorticoids inhibit Wnt signalling and suppress osteoblast differentiation and function, promote apoptosis of osteoblasts and osteocytes, increase osteoclast survival, reduce intestinal calcium absorption and increase urinary calcium losses. The dominant early effect is depressed bone formation on trabecular surfaces, so vertebral collapse occurs early. Option B is wrong because glucocorticoids increase, not decrease, renal calcium excretion, and option A is wrong because they impair 1-alpha hydroxylation.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.