Effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons.
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.


BACKGROUND
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.
Ott
S M
SM
University of Washington, 1959 NE Pacific Street, P. O. Box 356426, Seattle, WA 98195-6426, USA. smott@u.washington.edu
LaCroix
A Z
AZ
Scholes
D
D
Ichikawa
L E
LE
Wu
K
K
D000368:Aged; D001639:Bicarbonates / Q000097:blood; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000652:urine; D002136:Calcium, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism*; D012737:Sex Factors
D001639:Bicarbonates; D002136:Calcium, Dietary; D008903:Minerals; D006852:Hydrochlorothiazide; D002118:Calcium