Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial.
OBJECTIVE
Thiazide diuretics reduce urine calcium excretion and might therefore reduce postmenopausal bone loss. In some, but not all, case-control studies, their use has been associated with a reduced incidence of hip fractures. We studied the effects of hydrochlorothiazide on bone loss in normal postmenopausal women.


METHODS
We performed a randomized, double-blind, 2-year trial of the effects of hydrochlorothiazide (50 mg per day) and placebo on bone mineral density in normal postmenopausal women. Participants were not required to have either low bone mineral density or hypertension. Bone mineral density was measured using dual-energy x-ray absorptiometry.


RESULTS
One hundred eighty-five women entered the study, of whom 138 completed 2 years of follow-up. In an intention-to-treat analysis, hydrochlorothiazide produced significant benefits on bone mineral density of the total body (between-group difference at 2 years of 0.8%, 95% confidence interval [CI]: 0.3% to 1.3%, P <0.0001), legs (0.9%, 95% CI: 0.2% to 1.7%, P <0.0001), mid-forearm (1.2%, 95% CI: 0.2% to 2.2%, P = 0.02), and ultradistal forearm (1.7%, 95% CI: 0.1% to 3.2%, P = 0.04). There was no effect in the lumbar spine (0.5%, 95% CI: -0.5% to 1.6%) or femoral neck (0.2%, 95% CI: 1.3% to 1.7%). The between-group changes tended to be greatest during the first 6 months, except in the mid-forearm where there appeared to be a progressive divergence. An as-treated analysis produced similar results. Urine calcium excretion and indices of bone turnover decreased in the thiazide group, but parathyroid hormone concentrations did not differ between the groups. Treatment was tolerated well.


CONCLUSIONS
Hydrochlorothiazide (50 mg per day) slows cortical bone loss in normal postmenopausal women. It may act directly on bone as well as on the renal tubule. The small size of the effect suggests that thiazides may have a role in the prevention of postmenopausal bone loss, but that they are not an appropriate monotherapy for treating osteoporosis.
Reid
I R
IR
Department of Medicine, University of Auckland, Auckland, New Zealand.
Ames
R W
RW
Orr-Walker
B J
BJ
Clearwater
J M
JM
Horne
A M
AM
Evans
M C
MC
Murray
M A
MA
McNeil
A R
AR
Gamble
G D
GD
D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004232:Diuretics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000378:metabolism; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000517:prevention & control*; D012016:Reference Values; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D002118:Calcium