The Effect of Thiazides on Bone Markers, Bone Mineral Density and Fractures

The literature data suggest a positive effect of thiazide diuretic treatment on bone health both by increasing bone mineral density and by decreasing the risk of fracture. The protective effect of thiazides seems to be linked both to the dosage and to the duration of treatment; moreover, the protective effects of thiazides in preserving bone mass and in decreasing the risk of fractures does not last long after discontinuation of treatment. Thiazides influence bone health by means of different mechanisms. In fact, they increase renal calcium reabsorption by inhibiting the sodium chloride cotransporter in the distal tubule, thus increasing sodium urinary excretion and decreasing urinary calcium excretion. Still, thiazides contribute to maintaining calcium homeostasis by increasing calcium intestinal absorption. Moreover, thiazides have a direct effect on bone cells, especially on osteoblast differentiation and bone mineral formation. Finally, it was suggested that thiazides prevent bone loss as they decrease the acid production by means of inhibition of carbonic anhydrase activity in the osteoclasts. The dual action shown by thiazides on both osteoblasts and osteoclasts could explain the reduced bone remodeling observed in patients taking these drugs, in the absence of changes in plasma parathyroid hormone levels. In conclusion, thiazides might play an interesting role in osteoporosis management, particularly in those patients affected by both hypertension and osteoporosis, but efficacy in reducing fractures and the safety of this treatment must still be evaluated by means of further randomized controlled clinical trials which have the reduction in fractures as primary outcomes.