Common Questions
Which antihypertensive agents have been shown in randomized controlled trials to increase bone mineral density (BMD)?
Thiazide diuretics have shown to improve bone mineral content in both men and women. Many observational studies (1-5) and several randomized controlled trials (6-8) have shown that bone density increases in both men and women while taking hydrochlorothiazide. These findings have been observed at both low and high doses of HCTZ and are independent of patient blood pressure status or PTH levels. However, the studies have shown that this effect disappears once the medication is discontinued (9).
- A randomized, double blinded, placebo-controlled trial of 320 elderly women and men compared bone density results between three groups; 12.5 mg of HCTZ a day, 25 mg of HCTZ a day, and placebo. Modest increases in BMD of the hip and spine were observed over 3 years. The investigators reasoned that the 3-year effect of HCTZ may accumulate over 10-20 years to explain the reduction for hip fracture found in epidemiologic studies (6).
- One study evaluated BMD at five sites in men taking a thiazide diuretic for hypertension. The patients taking thiazides were found to have significantly greater bone mineral content at all sites evaluated as compared to non-users. Furthermore, patients with untreated hypertension had comparable BMD to non-hypertensive patients, suggesting that increased BMD among thiazides was not attributed to hypertension (1).
- Wasnich RD, Benfante RJ, et al. Thiazide effect on the mineral content of bone. New England Journal of Medicine 1983; 309(6): 344-7.
- Sigurdsson G, Franzson L. Increased bone mineral density in a population-based group of 70-year-old women on thiazide diuretics, independent of parathyroid hormone levels. Journal of Internal Medicine 2001; 250(1): 51-6.
- Wasnich RD, et al. A randomized, double-masked, placebo controlled-trial of chlorthalidone and bone loss in elderly women. Osteoporosis Int 1995; 5(4): 247-51.
- Cauley JA, Cummings S, Seeley DG, Black D, Browner W, Kuller LH, Nevitt MC. Effects of thiazide dirutic on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group. Ann Intern Med 1993; 118(9): 666-73.
- Morton DJ, Barrett-Connor EL, Edelstein SL. Thiazides and Bone Mineral Density in Elderly Men and Women. American Journal of Epidemiology 1994; 139(11): 1107-1115.
- LaCroix A, Ott SM, et al. Low-dose hydrochlorothiazide and preservation of bone mineral density n older adults: a randomized, double blind, placebo-controlled trial. Annals of Internal Medicine 2000; 133(7): 516-26.
- Bolland MJ, Ames RW, Horne AM, et al. The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporosis Int 2007; 18(4): 479-86.
- Reid IR, Ames RW, Orr-Walker BJ, Clearwater JM, et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial. Am J Med 2000; 109(5): 362-70.
- Felson DT, Sloutskis D, Anderson JJ, Anthony JM and Kiel DP. Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study 1991; 265(3): 370-3.