Hydrochlorothiazide inhibits osteoclastic bone resorption in vitro.
Long-term thiazide diuretic use is associated with higher bone mineral density and reduced hip fracture rates, which are attributed to increased serum calcium levels and decreased parathyroid activity that lead to decreased bone resorption. The present study shows that 1-100 microM hydrochlorothiazide (HCTZ) dose dependently inhibits bone resorption by isolated rat osteoclasts in the bone slice assay with an IC50 of approximately 20 microM. At these concentrations, HCTZ did not affect osteoclast survival on bone slices and had no effect on the proliferation of UMR-106 rat osteoblasts, indicating that the compound is not cytotoxic. However, such concentrations of HCTZ are unlikely to be achieved in man where therapeutic doses are usually 12.5-100 mg/day. That the in vitro effect of HCTZ on bone resorption may be due to inhibition of osteoclast carbonic anhydrase is discussed.
Hall
T J
TJ
Ciba-Geigy Ltd., Research Department, Basel, Switzerland.
Schaueblin
M
M
D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D066298:In Vitro Techniques; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D006852:Hydrochlorothiazide; D002118:Calcium