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Acute effects of bisphosphonates on new and traditional markers of bone resorption

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Abstract

Bisphosphonates are known to be potent inhibitors of osteoclast activity and their only clinically relevant effect in the short-term is the selective inhibition of bone resorption. The purpose of this study was to compare the response to the intravenous administration of two bisphosphonates, clodronate and alendronate, of several biochemical markers of bone resorption, including tartrate-resistant acid phosphatase (TRAP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) in serum and hydroxyproline (OHP), free pyridinium cross-links (Pyr), and crosslinked N-telopeptides of collagen I (NTx) in urine. The study was carried out on 11 osteoporotic and 12 Pagetic subjects of both sexes, treated with clodronate (600 mg/day for 2 days) or alendronate (5 mg/day for 2 days), and monitored for 28 days after bisphosphonate administration. All the urinary markers of bone resorption showed a prompt decline after bisphosphonates, with maximum reductions after 7–14 days: Pyr decreased by 43%±9% and 42%±22% (mean ± SD), respectively in osteoporotic and pagetic subjects, OHP by 51%±14% and 51%±20%, and NTx by 55%±15% and 65%±26%. In the osteoporotic group, the urinary markers began to increase again at 30 days, though still remaining well below the basal level, whereas in the pagetic group, the excretion of all markers remained depressed until the end of the observation period. The reduction of NTx was significantly greater than that of Pyr and OHP in pagetic patients (P<0.05) and tended to be greater than that of Pyr in osteoporotic patients (p=0.07). Serum levels of TRAP decreased slightly, with a maximum reduction after 7 days of 16%±22% and 21%±11% in osteoporotic and pagetic subjects, respectively. Serum ICTP levels showed a slow and limited decrease, with minimal values after 14 days in pagetic subjects (-9%±21%; p=NS) and 30 days in osteoporotic patients (13%±4%; P<0.05). The cumulative changes of all urinary markers, expressed as area under the curve, were significantly greater than those observed for serum markers (P<0.01). In conclusion, these results indicate that the new markers of bone resorption differ in their capacity to reflect the acute inhibition of bone resorption following the I.V. administration of bisphosphonates. The use of bisphosphonates may be a useful means to test new markers of bone resorption.

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Pedrazzoni, M., Alfano, F.S., Gatti, C. et al. Acute effects of bisphosphonates on new and traditional markers of bone resorption. Calcif Tissue Int 57, 25–29 (1995). https://doi.org/10.1007/BF00298992

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  • DOI: https://doi.org/10.1007/BF00298992

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