Intermittent parathyroid hormone fails to stimulate osseointegration in diabetic rats

Diabetes is considered a risk factor in the osseointegration of dental implants, which suggests that these patients might benefit from anabolic therapies. Preclinical studies, including investigations by this research group, revealed that intermittent administration of parathyroid hormone (PTH) stimulates bone formation on the surface of titanium implants under physiological conditions. However, the anabolic effect of PTH on osseointegration under the hyperglycemic condition of diabetes is unknown.

The ability of PTH to stimulate osseointegration was investigated in 40 female Wistar rats that were randomly divided into the following treatment groups: diabetes, diabetes plus PTH, control, and control plus PTH. Diabetes was induced by intraperitoneal injection of streptozotocin (45 mg/kg) at 1 week before implantation. Rats received PTH at a dose of 60 μg/kg or a vehicle by subcutaneous injection starting at the day of implant insertion into the tibia. Histomorphometric analysis was performed after 4 weeks.

The medullary peri-implant bone area significantly increased in rats receiving PTH in comparison with the control group (41±12% to 20±12%; P<0.01). Moreover, there was an increased bone-to-implant contact (BIC) area in animals treated with PTH (47±18% to 27±16%; P<0.05). In contrast, diabetic rats failed to benefit from the anabolic treatment. A similar peri-implant bone area occurred in the diabetes group, independent of treatment with PTH (13±9% to 15±6%; P>0.05). Moreover, PTH did not affect the BIC area under hyperglycemic conditions (16±12% to 16±8%; P>0.05). No significant changes were observed in the cortical compartment of all groups.

These results demonstrate that the metabolic characteristics of the diabetic rats produced a condition that was unable to respond to PTH treatment. These findings led us to hypothesize that metabolic control of diabetes might be a critical determinant when diabetic patients are undergoing anabolic therapy to enhance osseointegration.