Common Questions
What is the mechanism by which corticosteriods cause osteoporosis?
The mechanism of corticosteroid-induced osteoporosis is multifactorial. These include the effects on calcium homeostasis, bone formation and resorption, and sex hormones (1).
Effect on calcium homeostasis Corticosteroids have a direct effect on calcium metabolism by inhibiting intestinal absorption of calcium and increasing urinary calcium excretion. By creating a net negative calcium balance in the body, corticosteroids induce a secondary hyperparathyroid state, thereby stimulating expression of PTH receptors in osteoblasts and enhancing osteoblast responsiveness to PTH. Corticosteroids also appear to decrease osteocalcin levels, therefore decreasing bone formation.
Inhibition of bone formation and enhanced bone resorption Corticosteroids have two direct effects on osteoclasts. Direct promotion of proliferation and differentiation of osteoclast precursors stimulates increased osteoclast formation. However, corticosteroids also appear to directly inhibit the bone-resorbing activity of mature osteoclasts. In vitro studies have illustrated that the increased proliferation of osteoclasts predominates over the inhibition of bone-resorbing activity, resulting in overall increase in osteoclast activity and bone resorption (1,2). Corticosteroids also promote osteoblast apoptosis and directly inhibit the synthetic function of osteoblasts, causing decreased osteoblast maturation and collagen formation (1,3).
Effect on sex hormones Corticosteroids appear to have both a direct effect on end-organ production of testosterone and suppression of ACTH causing decreased gonadotropin production (3).
There is no evidence to support a threshold below which corticosteroids have no effect on bone metabolism, so it is always recommended to use the lowest possible dose. The rate of steroid-induced bone loss is greatest in the first 3-6 months of therapy, so preventive measures are imperative for maximal risk reduction. After discontinuing corticosteroids, a rebound of osteoblastic function and new bone formation usually occurs, though bone mass may not reach pre-treatment levels (1).
- Tannirandorn P, Epstein S. Drug-Induced Bone Loss. Osteoporosis International 2000; 11: 637-659.
- Hirayama T, et al. Effect of corticosteroids on human osteoclast formation and activity. Journal of Endocrinology 2002; 175: 155-163.
- National Osteoporosis Society. Guidelines on glucocorticoid-induced osteoporosis. 2002. Available online.