OsteoEd

Common Questions

What medicines should be used to treat corticosteroid-induced osteoporosis?

Multiple medications have been shown to improve bone mineral density in postmenopausal osteoporosis, but very few have been tested specifically for the prevention and treatment of corticosteroid-induced osteoporosis. Up until recently, only alendronate and risedronate had been FDA approved for the treatment of glucocorticoid-induced osteoporosis in both men and women (for those receiving >7.5 mg prednisone daily).

Several large randomized controlled clinical trials have shown a significant increase in BMD and decrease in fracture risk in patients receiving corticosteroids treated with alendronate and risedronate (1-5). All the clinical guidelines support the use of these bisphosphonates as first-line therapy for prevention and treatment of corticosteroid-induced osteoporosis in men and postmenopausal women (6-12).

Zoledronic acid has now been FDA approved for individuals who are expected to be on steroids for at least 12 months.

However, there are still important questions to be answered regarding bisphosphonates. Bisphosphonates have not been well studied beyond use for ten years and none of the guidelines reviewed discussed the recommended duration of bisphosphonate therapy. Bisphosphonates have not been shown to significantly increase bone mineral density for postmenopausal patients already on hormone replacement therapy, but this combined therapy has not been evaluated in postmenopausal women on corticosteroids (13). Several guidelines also caution against the use of bisphosphonates in premenopausal women due to the risk of teratogenic effects, but no studies have helped to clearly define the role of osteoporosis prevention and treatment in premenopausal women on corticosteroids and which medications are best to use in this specific population (9,10).

All osteoporosis prevention and treatment guidelines for corticosteroid-induced osteoporosis support the use of calcium and vitamin D supplementation. Randomized controlled trials have shown that calcium and vitamin D supplementation prevent bone loss in rheumatoid arthritis patients on long-term low-dose glucocorticoid therapy (mean prednisone dose 5.6mg daily) (14). Neither calcium alone nor vitamin D alone has been shown to have similar effects.

Other FDA approved medications for prevention and/or treatment of postmenopausal osteoporosis may be considered if the patient is unable to take a bisphosphonate:

  • Calcitonin

  • While calcitonin has been approved by the FDA for treatment of postmenopausal osteoporosis, it is not FDA approved for treatment of corticosteroid-induced osteoporosis. Studies disagree on the efficacy of calcitonin in corticosteroid-induced osteoporosis; therefore guidelines agree there may be some utility of calcitonin, but certainly not as a first-line treatment or prevention therapy for corticosteroid-induced osteoporosis (6-12).

  • Hormone replacement therapy (HRT)

  • Few studies have evaluated the use of HRT in prevention or treatment of corticosteroid-induced osteoporosis. A randomized controlled trial of transdermal HRT versus calcium showed increased bone mineral density in postmenopausal women with rheumatoid arthritis on glucocorticoid therapy (15). HRT has also been shown in randomized controlled trials of postmenopausal women to improve bone mineral density with similar efficacy to the bisphosphonate, alendronate (13). However, in light of the Women's Health Initiative study results released in July 2002, the role of HRT in corticosteroid osteoporosis has decreased significantly. Whereas HRT was once considered the "gold standard" for postmenopausal osteoporosis treatment and prevention, now the National Osteoporosis Society only recommends use of HRT in patients who also suffer from symptoms of menopause or who cannot take alternate osteoporosis medications (16).

    All guidelines reviewing prevention and treatment of corticosteroid-induced osteoporosis in men, recommend testosterone replacement therapy for men with low serum levels of testosterone (6-12).

  • Selective estrogen receptor modulator (SERM) - Raloxifene

  • No studies have evaluated the effect of SERMs in the prevention and treatment of corticosteroid-induced osteoporosis. However, the SERM raloxifene has been shown in randomized, placebo-controlled trials to decrease the risk of postmenopausal fractures, especially moderate/severe vertebral fractures (17). In comparison to bisphosphonates, raloxifene has been shown to have less improvement on BMD in postmenopausal women compared to alendronate (18).

  • Parathyroid hormone (PTH) - Teriparatide

  • PTH, an anabolic agent, has been shown to reduce vertebral fractures in postmenopausal women, however, there is no fracture data regarding PTH in glucocorticoid-treated patients. One study showed that postmenopausal osteoporotic women receiving prolonged glucocorticoids and HRT that were treated for 1 year with PTH had an 11% increase in lumbar spine bone mass. one year after discontinuation of PTH, lumbar spine bone mass remained stable and total hip bone mass increased 5% over baseline levels, while the patients continued to receive HRT (19).

  1. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, et al. Alendronate for the treatment and prevention of glucocorticoid-induced osteoporosis. New England Journal of Medicine 1998; 339: 292-299.
  2. Reid DM, Hughes RA, Laan RF, Sacco-Gibson NA, Wenderoth DH, Adami S, et al. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. Journal of Bone and Mineral Research 2000; 15: 1006-1020.
  3. Adachi JD, Bensen WG, Brown J, Hanley D, Hodsman A, Josse R, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. New England Journal of Medicine 1997; 337: 382-387.
  4. Cohen S, Levy RM, Keller M, Boling E, Emkey RD, Greenwald M, et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel group study. Arthritis and Rheumatism 1999; 42: 2309-2318.
  5. Adachi JD, Saag KG, Delmas PD, Liberman UA, Emkey RD, Seeman E, et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double blind, placebo-controlled extension trial. Arthritis and Rheumatism 2001; 44: 202-211.
  6. National Osteoporosis Society. Guidelines on glucocorticoid-induced osteoporosis. 2002. Available online.
  7. Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW, Johnston CC, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract 2003; 9;6: 544-564.
  8. Institute for Clinical Systems Improvement (ICSI). Diagnosis and treatment of osteoporosis. Institute for Clinical Systems Improvement (ICSI) 0000; Bloomingto.
  9. American College of Rheumatology. Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis and Rheumatism 2001; 44;7: 1496-1503.
  10. Yeap SS, Hosking DJ. Management of corticosteroid-induced osteoporosis.. Rheumatology 2002; 41: 1088-1094.
  11. Adler RA, Hochberg MC. Suggested guidelines for evaluation and treatment of glucocorticoid-induced osteoporosis for the Department of Veterans Affairs. Archives of Internal Medicine 2003; 163: 2619-2623.
  12. American Gastroenterological Association. American Gastroenterological Association Medical Position Statement: Guidelines on osteoporosis in gastrointestinal diseases. Gastroenterology 2003; 124;3: 791-794.
  13. Evi (o) S, Tiitinen A, Laitinen K, Ylikorkala O, Valimaki. Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis. Journal of Clinical Endocrinology and Metabolism 2004; 89;2: 626-631.
  14. Buckley LM, Leib ES, Cartularo S, Vacek PM, Cooper SM. Calcium and vitamin D supplementation prevents bone loss in the spine secondary to low dose corticosteroids in patients with rheumatoid arthritis: a randomized, double-blind, placebo controlled trial. Annals of Internal Medicine 1996; 125: 961-986.
  15. Hall GM, Daniels M, Doyle DV, Spector TD. Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum 1994; 37: 1499-505.
  16. National Osteoporosis Society News Database. What the National Osteoporosis Society says about HRT. 0000. Available online.
  17. Siris E, Adachi JD, Lu Y, Fuerst T, Crans GG, Wong M, Harper KD, Genant HK. Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: Results from the MORE Study. Osteoporosis International 2002; 13: 907-913.
  18. Sambrook PN, Geusens P, Ribot C, Solimano JA, Ferrer-Barriendos J, Gaines K, et al. Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International. Journal of Internal Medicine 2004; 255: 503-511.
  19. Lane NE, Sanchez S, Modin G, Genant HK, Pierini E, Arnaud CD. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000; 15: 944-51.
Last updated 2009-07-03