Hip fractures are a disabling and costly public health problem in older adults that are projected to nearly double in number by the year 2020; yet available alternatives for preventive interventions remain severely limited. Use of thiazide diuretics has been consistently associated with higher levels of bone density in cross-sectional studies and with a reduced risk of hip fracture in several epidemiologic studies. However, the evidence from observational investigations is inconclusive because of the many differences between thiazide users and non-users in non-randomized studies. The long-term objective of this research is to determine the role of thiazide diuretic therapy in prevention of bone loss and fracture in older adults aged 60-79 years. A double blind, randomized controlled trial of the effect of low dose thiazide diuretic therapy on rate of bone loss will be conducted in 270 normotensive elderly women and men who are not currently treated for high blood pressure. Older adults will be recruited from a population base of approximately 53,100 HMO enrollees. Women and men will eligible if they are normotensive and not taking any anti-hypertensive medications, if their bone density at the hip is between the 5th and 95th percentiles for their sex and age group, and if they are basically in good health. Eligible adults will be randomized to one of three groups: 1) 25 mg/day if hydrochlorothiazide; 2) 12.5 mg/day of hydrochlorothiazide; or 3) placebo. The primary trial endpoint, bone mineral density, will be measured at the hip, AP lumbar spine, and using whole body calcium techniques at baseline and every 6 months for 3 years of follow-up using dual energy X-ray absorptiometry. Secondary aims of the proposed trial are: 1) to elucidate mechanisms by prospectively determining the effects of low dose thiazide therapy on indices of bone metabolism, and 2) to prospectively determine the short and long-term effects of low dose thiazide therapy on cardiovascular risk factors, incidence rates of falls and functional status in elderly persons. If the results of this randomized trial confirm an effect of thiazide diuretic therapy on preserving bone density in older adults, then the use of thiazides may prove to be a safe, effective, low cost means of preventing osteoporotic fractures in our growing older population.
| Ott, S M; LaCroix, A Z; Scholes, D et al. (2008) Effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons. Osteoporos Int 19:1315-22 |
| Ott, Susan M; LaCroix, Andrea Z; Ichikawa, Laura E et al. (2003) Effect of low-dose thiazide diuretics on plasma lipids: results from a double-blind, randomized clinical trial in older men and women. J Am Geriatr Soc 51:340-7 |
| LaCroix, A Z; Ott, S M; Ichikawa, L et al. (2000) Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 133:516-26 |
