Short-term administration of the bisphosphonate ibandronate increases bone volume and prevents hyperparathyroid bone changes in mild experimental renal failure.
BACKGROUND
Bisphosphonates (BP) are potent antiresorptive agents that have been used successfully in several bone diseases associated with hyperresorption. Hyperresorption, hypercalcemia, and osteoporosis are frequent findings in patients with renal failure or after renal transplantation. The present study was carried out to determine the effects of a new BP, ibandronate, on bone in a state of normal vs. moderately impaired renal function.


METHODS
Forty 90-day-old female rats were either 2/3 nephrectomized (Nx, n = 20) or sham-operated (Sham, n = 20). Half of the Nx and Sham rats received either ibandronate (1.25 microg/rat s.c.) or vehicle once weekly for three weeks. Before euthanasia, blood drawings were performed and 24-hr urine was collected. Femurs were analyzed by bone histomorphometry.


RESULTS
Serum creatinine, parathyroid hormone, and osteocalcin levels were equally higher in Nx rats given ibandronate or vehicle than in Sham rats. There was no difference in serum calcium, phosphorus, alkaline phosphatase, and urinary creatinine among the groups. Ibandronate-treated rats had lower urinary calcium and deoxypyridinoline crosslink levels than their Sham counterparts. Ibandronate-treated rats had higher bone volume than vehicle-treated animals. Ibandronate prevented the increase in erosion depth and bone turnover in Nx rats.


CONCLUSIONS
BPs such as ibandronate represent potentially useful tools in the treatment of certain facets of renal bone disease. Indications for BP therapy may include treatment of osteoporosis, hypercalcemia, and/or extraosseous calcifications. Optimal dose and frequency of BP administration need to be determined in these patients.
Department of Internal Medicine, University of Kentucky Lexington, 40536-0298, USA.
Z
Z
Geng
M C
MC
Monier-Faugere
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F
Bauss
H H
HH
Malluche
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism / Q000473:pathology*; D003404:Creatinine / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism / Q000473:pathology*; D000077557:Ibandronic Acid; D007676:Kidney Failure, Chronic / Q000150:complications*; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D004164:Diphosphonates; D010281:Parathyroid Hormone; D015675:Osteocalcin; D010758:Phosphorus; D003404:Creatinine; D000469:Alkaline Phosphatase; D002118:Calcium; D000077557:Ibandronic Acid