What is the role of bisphosphonates in the treatment of hypercalciuria?

Updated: Jun 02, 2021
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva) have become useful in the treatment of hypercalciuria and hypercalcemia. These agents are particularly helpful in cases of hyperparathyroidism in which parathyroid surgery cannot be performed or medical therapy is desired.

Bisphosphonates are analogues of pyrophosphate with a high affinity for the hydroxyapatite of bone, especially in areas of rapid turnover and bone resorption. These drugs inhibit osteoclast activity, which causes a net increase in bone density, calcium deposition, and mineralization. Preferential binding to osteoclasts is roughly 10 times greater than osteoblastic binding.

Although bisphosphonates are clearly helpful in cases of overt hypercalcemia and hyperparathyroidism, their usefulness in the long-term treatment of hypercalciuria in recurrent stone formers is unproved. These agents may be most useful in hypercalciuric stone formers in whom a history of decreased bone density or other evidence of osteoporosis, such as elevated osteocalcin levels, is present. Combination therapy with thiazides would be expected to be particularly beneficial. Bisphosphonates can also be helpful in difficult cases of hypercalciuria when other measures are unsuccessful or poorly tolerated.

Bisphosphonate with thiazide

In a study of 70 patients with recurrent lithiasis, hypercalciuria, and bone-density loss, Arrabal-Polo et al found that after 2 years of treatment the patients receiving a combination of bisphosphonate and thiazide had a significantly greater decrease in calciuria and improvement in bone density than did patients treated with bisphosphonate alone. Half of the patients in the study were treated with 70 mg/wk of alendronate, while the other 35 patients were treated with a combination of 70 mg/wk of alendronate and 50 mg/day of hydrochlorothiazide. [35]

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