Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model
Fernando B. Vergara-Hernandez, Brian D. Nielsen, John M. Popovich, Char L. Panek, Alyssa A. Logan, Cara I. Robison, Richard A. Ehrhardt, Tyler N. Johnson, Nicholas J. Chargo, Thomas H. Welsh, Amanda N. Bradbery, Jessica L. Leatherwood, Aimee C. Colbath

TL;DR
Clodronate disodium had no measurable effects on bone metabolism in exercising juvenile sheep, despite changes due to growth and exercise.
Contribution
Demonstrates that clodronate disodium does not affect bone metabolism in juvenile, active large animals at low doses.
Findings
Clodronate disodium had no measurable effects on bone turnover or microstructure in juvenile sheep.
Changes in bone biomarkers and microstructure were likely due to growth and exercise, not the drug.
Low CLO doses in large animals may not impact bone, suggesting potential for analgesic use without bone changes.
Abstract
Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG…
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Taxonomy
TopicsBone health and treatments · Bone health and osteoporosis research · Bone fractures and treatments
