Administration of parathyroid hormone, prostaglandin E2, or 1-alpha,25-dihydroxyvitamin D3 restores the bone inductive activity of rhBMP-2 in aged rats.
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.
Kabasawa
Yuhji
Y
Oral Surgery, Department of Oral Restitution, Division of Oral Health Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Asahina
Izumi
I
Gunji
Akemi
A
Omura
Ken
K
D000375:Aging; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D019485:Bone Morphogenetic Proteins; D004343:Drug Implants; D006133:Growth Substances; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D000469:Alkaline Phosphatase; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium