Affiliation:
1. Laboratory for Experimental Medicine and Endocrinology and Department of Obstetrics and Gynecology, Katholieke Universiteit Leuven Belgium Clinical Research Group for Bone Metabolism, Academic Hospital Utrecht, The Netherlands Institut National de la Sante et de la Recherche Medicale U120 Le Vésinet, France Department of Orthopedics, Mount Sinai School of Medicine New York, New York
Abstract
The effect of long-term diabetes mellitus on bone and mineral metabolism was studied in BB rats. Diabetic rats were treated with 1 U of long-acting insulin every other day for 12 wk and compared with nondiabetic littermates. Urinary calcium excretion was increased > 10-fold, but serum total and diffusible calcium remained normal. Serum concentrations of both 1α,25-dihydroxyvitamin D3 and vitamin D–binding protein were significantly decreased in diabetic rats. The intestinal calbindin-D 9K concentration was decreased by nearly 50%, and active duodenal calcium absorption was totally abolished. Trabecular bone volume measured in the tibial metaphysis was decreased by 44%, and the osteoblast and osteoid surfaces were <10% of values observed in control rats, whereas the osteoclast surface was unchanged by diabetes. The daily bone formation (bone mineral apposition rate) measured by labeling twice with calcein was decreased by 86% in diabetic rats. The serum concentration of osteocalcin, a biochemical marker of osteoblast function, was similarly decreased (mean ± SE 23 ± 3 and 62 ± 4 μg/L in diabetic [n = 15] and nondiabetic [n = 15] rats, respectively). Serum osteocalcin was significantly correlated with the serum concentration of insulinlike growth factor I (r = 0.89, P < 0.001). Bone strength measured as the energy needed to fracture the femur was markedly decreased (5.3 ±1.4 and 8.4 ± 1.3 N · m · degree in diabetic and nondiabetic rats, respectively; P < 0.01). These histological, chemical, and biomechanical data clearly indicate that long-standing diabetes in BB rats results in severe low-turnover osteoporosis probably related to decreased osteoblast recruitment and/or function.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
135 articles.
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