Thiazide Users Research Articles

Thiazide Diuretic Agents and the Incidence of Hip Fracture

Thiazide diuretic agents lower the urinary excretion of calcium. Their use has been associated with increased bone density, but their role in preventing hip fracture has not been established. We prospectively studied the effect of thiazide diuretic agents on the incidence of hip fracture among 9518 men and women 65 years of age or older residing in three communities. At base line, 24 to 30 percent of the subjects were thiazide users. In the subsequent four years, 242 subjects had hip fractures. The incidence rates of hip fracture were lower among thiazide users than nonusers in each community; the Mantel-Haenszel relative risk of hip fracture, adjusted for community and age, was 0.63 (95 percent confidence interval, 0.46 to 0.86). The protective effect of the use of thiazides was independent of sex, age, impaired mobility, body-mass index, and current and former smoking status; the multivariate adjusted relative risk of hip fracture was 0.68 (95 percent confidence interval, 0.49 to 0.94). Furthermore, the protective effect was specific to thiazide diuretic agents, since there was no association between the use of antihypertensive medications other than thiazides and the risk of hip fracture. These prospective data suggest that in older men and women the use of thiazide diuretic agents is associated with a reduction of approximately one third in the risk of hip fracture.

Thiazide Diuretic Agents and the Incidence of Hip Fracture

Thiazide diuretic agents lower the urinary excretion of calcium. Their use has been associated with increased bone density, but their role in preventing hip fracture has not been established. We prospectively studied the effect of thiazide diuretic agents on the incidence of hip fracture among 9518 men and women 65 years of age or older residing in three communities. At base line, 24 to 30 percent of the subjects were thiazide users. In the subsequent four years, 242 subjects had hip fractures. The incidence rates of hip fracture were lower among thiazide users than nonusers in each community; the Mantel-Haenszel relative risk of hip fracture, adjusted for community and age, was 0.63 (95 percent confidence interval, 0.46 to 0.86). The protective effect of the use of thiazides was independent of sex, age, impaired mobility, body-mass index, and current and former smoking status; the multivariate adjusted relative risk of hip fracture was 0.68 (95 percent confidence interval, 0.49 to 0.94). Furthermore, the protective effect was specific to thiazide diuretic agents, since there was no association between the use of antihypertensive medications other than thiazides and the risk of hip fracture. These prospective data suggest that in older men and women the use of thiazide diuretic agents is associated with a reduction of approximately one third in the risk of hip fracture.

Differential effects of thiazide and estrogen upon bone mineral content and fracture prevalence

Individual and combined effects of thiazides and estrogens upon bone mineral content at four sites (proximal radius, distal radius, os calcis, lumbar spine) and fracture prevalence were assessed retrospectively in 993 postmenopausal women. Compared with untreated women, use of thiazide alone was associated with significantly higher bone mineral content (P less than or equal to .01); nonspine fracture prevalence in this group was reduced by one-half (P = .07). Estrogen alone also was associated with significantly higher bone mineral content (P less than or equal to .0001); nonspine fracture prevalence was reduced by almost one-half (P = .07). The users of both estrogen and thiazide had the highest bone mineral content levels, which were significantly different than the thiazide-only group at four bone sites (P less than or equal to .001), and the estrogen-only group for three bone sites (P less than or equal to .05). Nonspine fracture prevalence for the users of both drugs was 17% that of the untreated group (P = .02). The relationships with spine fracture prevalence were less consistent; however, estrogen users appeared to have a lower spine fracture prevalence rate and higher spinal bone mineral content than thiazide users. These findings suggest a potential role for thiazides in the prevention of osteoporosis.

Thiazide effect on the mineral content of bone.

The thiazide diuretics are known to cause calcium retention. In order to study the effect of thiazides on bone mineralization, we have measured the mineral content of bone at five sites (the distal radius, the distal ulna, the proximal radius, the proximal ulna, and the os calcis) in 1368 men with a mean age of 68 years, including 323 who were taking thiazides for hypertension. The results were adjusted for age and body-mass index. Thiazide users had significantly more bone mineral content at all five sites than did non-users. Untreated hypertensive patients and persons without hypertension had comparable bone mineral content, indicating that the higher mineral content found among thiazide users is related to the drug and not to the underlying hypertension. These findings suggest the possibility of a preventive or therapeutic role for thiazides in osteoporosis.