Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate.
The bone loss and hypercalciuria induced by immobilization or the decreased gravitational forces of space are well described. Using a model of bedrest immobilization, the ability of a potent aminobisphosphonate, alendronate, to avert hypercalciuria and stone-forming propensity was tested. Sixteen male subjects participated in a randomized, placebo-controlled trial in which they received either 20 mg of alendronate or placebo 2 weeks prior to and during 3 weeks of strict bedrest. Parameters of bone and calcium metabolism and urinary crystallization of stone-forming salts were measured before and at the end of bedrest. In the placebo group, bedrest increased urinary calcium (209 +/- 47 to 267 +/- 60 mg/day, p < 0.01) and the saturation of calcium phosphate. Before bedrest, the alendronate group had a significantly lower serum calcium (8.8 +/- 0.4 vs. 9.6 +/- 0.5 mg/dl, p < 0.01) and higher serum PTH (62.4 +/- 33.1 vs. 23.1 +/- 7.5 pg/ml, p < 0.01) compared with the placebo group. Moreover, the alendronate group had a lower urinary calcium (75 +/- 41 mg/day) and saturation of calcium oxalate and calcium phosphate. These effects of alendronate were sustained during bedrest. Following bedrest in the alendronate group, urinary calcium rose to 121 +/- 50 mg/day, a value less than that in the placebo group before or during bedrest. Similarly, urinary saturation of calcium oxalate and calcium phosphate rose with bedrest in the alendronate-treated patients but remained lower than values obtained in placebo-treated patients before or during bedrest. Alendronate inhibits bone mineral loss and averts the hypercalciuria and increased propensity for the crystallization of stone-forming calcium salts which occurs during 3 weeks of strict bedrest.
Ruml
L A
LA
Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, USA.
Dubois
S K
SK
Roberts
M L
ML
Pak
C Y
CY
D000328:Adult; D019386:Alendronate; D001510:Bed Rest / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007103:Immobilization / Q000009:adverse effects*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D014545:Urinary Calculi / Q000517:prevention & control*
D015415:Biomarkers; D004164:Diphosphonates; D010281:Parathyroid Hormone; D010758:Phosphorus; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate