Administration of Parathyroid Hormone,Prostaglandin E 2,or 1-alpha,25-Dihydroxyvitamin D 3 Restores the Bone Inductive Activity of rhBMP-2 in Aged Rats

Abstract

Bone morphogenetic protein (BMP) induces bone formation in young rodents, but aging causes a reduction in the bone-forming ability of BMP. Most patients who require bone reconstruction are relatively old. Accordingly, we examined whether anabolic hormones could restore the bone inductive activity of rhBMP-2 in aged rats. rhBMP-2 in a carrier pellet was implanted subcutaneously in both 4- and 50-week-old female Wistar rats. PTH, PGE₂, or 1,25(OH)₂D₃ was injected every day during the period of BMP implantation. The pellets were harvested, and were examined both histologically and biochemically 2 weeks after implantation. Bone-forming ability was measured by alkaline phosphatase (ALP) activity and calcium (Ca) content. Pellets in 50-week-old rats showed a significant reduction in bone formation compared to pellets in 4-week-old rats. However, daily injections of PTH into 50-week-old rats restored both ALP activity (103 ± 4.6%) and Ca content (105 ± 2.6%). 1,25(OH)₂D₃ and PGE₂ also restored Ca content (103 ± 4.5% and 98 ± 3.8%, respectively) and stimulated ALP activity (142 ± 2.3% and 133 ± 3.6%). These results show that the administration of these hormones restores bone-forming ability in aged rats. A combination treatment of these hormones with rhBMP-2 might be applicable to the reconstruction of bone defects in elderly patients.