Effect of thiazide on rates of bone mineral loss: a longitudinal study.

Abstract

Objective-To determine the effect of thiazide diuretic drugs on rates of bone mineral loss.Design-Longitudinal, observational study with a mean follow up of five years.Setting-Hawaii Osteoporosis Center, Honolulu. Subjects-1017 Japanese-American men born between 1900 and 1920, of whom 378 were treated for hypertension (study group) and 639 did not have hypertension (control group)+ Intervention-Thiazide diuretics were taken by 325 men for a mean of 11.9 years; 53 men took antihypertensive drugs other than thiazides.Main outcome measure-Rate of bone loss estimated from serial photon absorptiometric scanning at three skeletal sites (calcaneus, distal radius, and proximal radius).Results-Rates of bone loss at all three sites were significantly reduced among thiazide users when compared with controls. The reductions in loss rate ranged from 28-8% (p=002) (distal radius) to 49-2% (p=-O OO5) (calcaneus) relative to the controls. At all three sites the men taking other antihypertensive drugs had faster loss rates (22-6-43.1%) than those of the controls but the difference was significant only for the distal radius.Conclusion-Thiazide diuretics slow the rate of bone loss in elderly men. IntroductionThe thiazide diuretics have diverse effects on electrolyte and mineral metabolism, including reduced urinary calcium excretion and increased urinary excretion of sodium, phosphate, and magnesium.' Previous cross sectional studies of both men and women have found greater bone mass and a reduced prevalence of fracture among patients taking thiazides.2`Two case-control studies have also found a reduced risk of hip fracture among patients taking thiazide.9' The only prospective study of the use of thiazide, however, was unable to show a persistent reduction in the rate of bone mineral loss." Thus a causal relation between the use of thiazide and a reduced rate of bone loss has not yet been established.The association between the use of thiazide and bone mass was first reported in a cohort of JapaneseAmerican men.2 We now report estimates of the effect of thiazide on rates of bone loss, based on a five year follow up of this cohort.

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

“…[1][2][3][4][5] Several antihypertensive drugs, including thiazides, b-blockers and angiotensin-converting enzyme inhibitors, decreased the risk of bone fractures and increased bone mineral density (BMD) clinically. [6][7][8][9][10] However, meta-analysis of observational studies on the effects of antihypertensive drugs on fracture outcomes demonstrated no significant association between fractures and calcium channel blockers (CCBs). [11][12][13] CCBs are divided into several subtypes, and non-dihydropyridinetype CCBs, but not dihydropyridine-type CCBs, are reported to reduce the risk of bone fractures through the inhibition of hyperparathyroidism-induced calcium uptake into osteoblasts and an elevation of intracellular calcium in osteoclasts.…”

Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters

“…Because it was also observed that expression of calcium transport proteins such as calcium channel TRPV5 and calbindin-D 28K was reduced, it was concluded that another potential explanation is that hypocalciuric effects of thiazides are due to extracellular volume contraction. This secondary effect of thiazides constitutes the basis for their use in treatment of calcium stone disease and may also explain protective effects of thiazides in osteoporosis (333,361,428). In addition, TSC indirectly modulates potassium and acid-base metabolism because secretion of these ions in renal collecting tubule is affected by NaCl delivery to this region of nephron.…”

Harmful effects of dietary salt in addition to hypertension

“…108,109 Thiazide diuretics which cause a reduction in calcium excretion when given to men and women with and without hypertension reduce the number of hip fractures. 110,111 Inasmuch as kidney stones are known to be associated with a raised urinary excretion of calcium it is probable that the salt-induced increase in urinary calcium excretion in SHR and essential hypertension contributes to their greater incidence of renal stones. [112][113][114] Conclusion: In normal humans salt intake influences urinary calcium excretion and bone turnover.…”