title: Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy.
abstract: Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Jinghan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Grynpas
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. Electronic address: jane.mitchell@utoronto.ca.
authors.forename: Jane
authors.initials: J
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000517:prevention & control*; D002113:Calcification, Physiologic / Q000187:drug effects; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D018483:Diaphyses / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D008297:Male; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009132:Muscles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D000077268:Pamidronate; D055114:X-Ray Microtomography
chemical_list: D004164:Diphosphonates; D005938:Glucocorticoids; D000077268:Pamidronate
keywords: Bisphosphonates; Bone mineral density; Bone strength; Creatine kinase; Duchenne muscular dystrophy; Glucocorticoids