Background

Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited.

Objective

To determine the effect of hydrochlorothiazide on rates of bone loss in older adults.

Design

Randomized, double-blind, placebo-controlled trial with 3-year follow-up.

Setting

A large health maintenance organization in western Washington State.

Participants

320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age.

Intervention

Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo.

Measurements

Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures.

Results

309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior-anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, -0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men.

Conclusions

In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.

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In this clinical trial of 12.5 or 25 mg/day of hydrochlorothiazide, the urine calcium showed significant decreases from placebo in men at one year, but the effects had waned by 3 years. Serum bicarbonate was consistently greater in the thiazide than in the placebo groups throughout the three years. These effects could be beneficial to the skeleton.

Introduction

Previous studies have shown increased bone density and reduced risk of fracture in patients taking thiazide diuretics. The long-term effects of low-dose thiazides on mineral metabolism have not been reported in normal subjects.

Methods

We conducted a randomized, double-blinded trial in normals aged 60-79 years, using hydrochlorothiazide 12.5 or 25 mg/d or placebo for three years. Subjects were encouraged to maintain calcium intake of 1,000 to 1,500 mg/day. Measurements of serum and urine calcium metabolism were done at baseline, six months, and yearly. Data were analyzed in 88 men and 177 women who had taken study medication. Adjusted change in the measurements from baseline to one and three years were compared among groups.

Results

The calcium intake increased in all groups. Urine calcium per day was significantly lower in thiazide than placebo groups in men at one year but not at three years; in women the changes were not significantly different. Serum bicarbonate was higher in thiazide compared to placebo groups at one and three years. No changes were seen in serum calcium, phosphate, parathyroid hormone, sodium or magnesium.

Conclusions

The results suggest that both increased calcium availability from a hypocalciuric effect and reduction in acid-induced bone buffering could be mechanisms for the beneficial skeletal effects.

Restricted activity days is the measure by which the 1990 health objectives for prevention of functional disability in older adults will be evaluated. Yet its significance in older populations is poorly understood. We evaluated its use as an outcome measure for a randomized trial designed to impact upon physical function in elderly HMO enrollees. As predicted, restricted activity days was more correlated with physical disability measures than with other health status measures. Distributional properties and rates of missing data were shortcomings.

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This study assessed associations between habitual caffeine intake and bone mass among young women. Analyses of the entire study population revealed no significant associations, while analyses restricted to women using depot medroxyprogesterone acetate (DMPA) showed modest inverse associations between caffeine intake and bone mineral content (BMC).

Introduction

Some previous investigations among postmenopausal women suggest an inverse relationship between caffeine intake and bone mass, yet studies of this association among young women are few.

Methods

The association between habitual caffeine intake and bone mass was evaluated prospectively in a population-based cohort of 625 females, aged 14 to 40 years, adjusting for relevant biological and lifestyle factors. Caffeinated beverage intake was self-reported, and bone mineral content (BMC) and bone mineral density (BMD) were measured at baseline and every 6 months throughout a 24-month follow-up period using dual-energy x-ray absorptiometry.

Results

Cross-sectional analyses revealed no significant differences in mean BMC or BMD at baseline. Mean percentage and absolute changes in BMC and BMD were not associated with caffeine use. Repeated measures analyses similarly showed no significant association between caffeine intake at baseline and mean BMC or BMD measured during follow-up. However, among women using depot medroxyprogesterone acetate (DMPA), modest inverse associations between caffeine and BMC (but not BMD) were detected.

Conclusions

Our data suggest that heavy habitual consumption of caffeinated beverages does not adversely impact bone mass among young women in general. Greater caffeine intake may be associated with lower BMC among DMPA users.

The purpose of this study was to compare biochemical markers of bone resorption and formation in young women using different hormonal contraceptive methods. Women aged 18-39 yr who were using depot medroxyprogesterone acetate (DMPA) contraception were recruited for the study; comparison women were matched by age and clinic location. There were 116 women using DMPA, 39 using oral contraceptives containing estrogen and progestin, and 72 not currently using hormonal contraceptives. Biochemical measurements were serum calcium, PTH and osteocalcin, and urine N-telopeptide. Bone density was measured using dual-energy x-ray absorptiometry. The N-telopeptide levels, adjusted for age and other risk factors, were 42.4 +/- 2.3 nmol/mmol creatinine in the DMPA group, 26.2 +/- 3.3 nmol/mmol in the oral contraceptive group, and 35.4 +/- 2.9 nmol/mmol in the nonusers; significant differences were seen in all pairwise comparisons. Osteocalcin levels showed the same pattern, although the difference between the DMPA users and nonusers was not statistically significant. There were no differences among groups in the PTH levels. The bone density at the spine was 1.086 +/- 0.085 g/cm(2) in the DMPA group, 1.103 +/- 0.095 g/cm(2) in the oral contraceptive group, and 1.093 +/- 0.090 g/cm(2) in nonusers (P = 0.051). The results suggest that in women using DMPA bone resorption exceeded bone formation.