Common Questions
What is the role of thiazide diuretics, beta blockers, and statins, in prevention of steroid-induced bone loss?
Thiazide diuretics, beta-blockers and statin medications have all been associated with higher bone density and lower fracture rates in post-menopausal women and men, though only thiazides have shown improvement of bone mineral density in randomized controlled trials.
Thiazides
While not proven to reduce specifically steroid-induced osteoporotic fractures, thiazide diuretics decrease renal calcium excretion, therefore they may be useful to treat steroid-induced hypercalciuria. Studies in normotensive men and women showed no significant adverse effects of thiazide use and a dose-dependent increase in bone mineral density at the spine and hip (1). While the magnitude of improvement in BMD was modest, it was greater than calcium and vitamin D supplementation alone (2). The risk reduction for fractures associated with thiazide use becomes statistically significant after one year of use, with a relative risk reduction of 0.46, but this protective effect disappears within four months of discontinuing the medication (3).
Many experts recommend measuring urinary calcium in all patients on corticosteroids and prescribing hydrochlorothiazide 25 mg daily (with potassium supplement if needed) if urinary calcium exceeds 300 mg/24 hours--even in the absence of hypertension (4). In patients beginning long-term corticosteroid treatment, urinary calcium should be measured 1 month after starting therapy (4). Thiazides should be avoided in patients taking high-dose vitamin D or calcitriol due to the risk of hypercalcemia.
Beta-blockers
The use of beta-blockers, both alone and in combination with thiazide diuretics, has also been shown in a large case control analysis to be associated with a significantly decreased fracture risk in both men and women. The proposed mechanism involves blocking the sympathetic nervous system effect on bone metabolism, thereby decreasing osteoclast numbers and activity (5).
Statins
HMG-CoA reductase inhibitors (statins) have also been associated with increased bone density and decreased fracture risk. Studies evaluating the mechanism of statins have shown these agents promote bone formation by stimulating osteoblasts, similar to the mechanism of bisphosphonates (6). Several prospective studies and observational studies show a significant increase in BMD and a clinically meaningful, but not statistically significant, decrease in fractures among statin users compared to postmenopausal women not on lipid-lowering medication or on nonstatin lipid-lowering medications (7). No randomized controlled trials have evaluated the ability of statins to prevent fractures, but the potential of statin medications to prevent osteoporosis will need to be further evaluated.
- LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. Annals of Internal Medicine 2000; 133;7: 516-526.
- Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. New England Journal of Medicine 1997; 337: 670-676.
- Schoofs MWCJ, van der Klift M, Hofman A, de Laet CEDH, Herings RMC, Stijnen T, et al. Thiazide diuretics and the risk for hip fractures. Annals of Internal Medicine 2003; 139;6: 476-483.
- Lane NE, Lukert B. The science and therapy of corticosteroid-induced bone loss. Endocrinol Metab Clin North Am 1998; 27: 465-483.
- Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of Beta-Blockers and risk of fractures. JAMA 2004; 292;11: 1326-1332.
- Solomon DH, Finkelstein JS, Wang PS, Avorn J. Statin lipid-lowering drugs and bone mineral density. Pharmacoepidemiology and Drug Safety 2005; 14(4): 219-26.
- Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Ensrud KE, et al. Use of Statins and Fracture. Archives of Internal Medicine 2004; 164: 146-152.