Bone Abstracts

The pathogenesis of skeletal fragility in diabetes mellitus is poorly defined and efficient therapies are limited. Zucker diabetic fatty (ZDF) rats with type 2 diabetes mellitus display low bone mass and delayed bone defect healing. We tested whether intermittent treatment with human parathyroid hormone 1–84 (PTH) increases bone mass and bone defect regeneration in diabetic rats.

A subcritical gap defect was created at the femur of 10 weeks old diabetic ZDF^fa/fa and non-diabetic ZDF^+/+ rats (n=10/group). PTH (75 μg/kg) or water as control were administered subcutaneously 5 days/week over the course of 12 weeks. Bone mass was assessed ex vivo at the non-operated femur and the lumbar vertebra by pQCT, and the filling of the femur gap was analyzed by micro-CT.

Diabetic rats had significantly lower total BMD at the metaphyseal area of the femur (−20%) and the lumbar vertebra (−11%) compared to non-diabetic rats. PTH treatment in diabetic rats resulted in increased bone mass at the femur (total BMD +10%, trabecular +46%) and lumbar spine (total BMD +18%, trabecular BMD +36%) compared to control-treated animals. Spinal BMD parameters of diabetic rats receiving PTH treatment were higher than those of non-diabetic rats treated with control. While non-diabetic rats filled 35% of the femoral defect, diabetic rats filled only 25%. PTH-treatment increased defect regeneration in the diabetic and non-diabetic groups by 49 and 8%, respectively. Intermittent PTH treatment resulted in increased serum levels of osteocalcin by 33 and 10% in diabetic and non-diabetic animals, respectively, and lower serum levels of CTX (−49 and −19%), consistent with a marked bone-anabolic effect.

In conclusion, intermittent PTH therapy is capable of reversing the adverse effects of type 2 diabetes mellitus on bone mass and delayed bone defect regeneration in rats.