Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats

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Abstract
Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone‐induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) −APD/triiodothyronine (−T3), (2) −APD/+T3, (3) +APD/−T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (−APD/+T3, 3.9 ± 0.25 μcat/liter and 23 ± 1.6 nM, respectively) than in control animals (2.53 ± 0.28 μkat/liter and 18.3 ± 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual‐energy x‐ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (−APD/+T3) BMD was significantly lower than in controls in the spine (0.201 ± 0.004 versus 0.214 ± 0.002 g/cm2, p < 0.05) and femur (0.204 ± 0.003 versus 0.218 ± 0.002, p < 0.05). In hyperthyroid rats pretreated with APD (+APD/+T3) BMD of the spine, femur, and total body was significantly higher than in controls (p < 0.001). Similar differences among groups were seen in femur calcium content. We conclude that hyperthyroid rats have an increased rate of bone turnover and bone loss that can be prevented by coadministration of a bisphosphonate.
Funding Information
  • U.S. Public Health Service Bureau of Health Professions Faculty Training Project in Geriatric Medicine (D31 PE91000)
  • Beth Israel Hospital General Clinical Research Center (M01RR01032)

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