UNLABELLED: DO was used in an aged mouse model to determine if systemically and/or locally administered rhIGF-I improved osteoblastogenesis and new bone formation. Local and systemic rhIGF-I treatment increased new bone formation. However, only systemic delivery produced measurable concentrations of rhIGF-I in the circulation. INTRODUCTION: Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model. MATERIALS AND METHODS: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouse IGF-I, human IGF-I, and osteocalcin were determined at the end of the study. RESULTS: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of human IGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhIGF-I-treated groups. CONCLUSIONS: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.
UNLABELLED: DO was used in an aged mouse model to determine if systemically and/or locally administered rhIGF-I improved osteoblastogenesis and new bone formation. Local and systemic rhIGF-I treatment increased new bone formation. However, only systemic delivery produced measurable concentrations of rhIGF-I in the circulation. INTRODUCTION:Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model. MATERIALS AND METHODS: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouseIGF-I, humanIGF-I, and osteocalcin were determined at the end of the study. RESULTS: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of humanIGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhIGF-I-treated groups. CONCLUSIONS: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.
Authors: G Zhao; M C Monier-Faugere; M C Langub; Z Geng; T Nakayama; J W Pike; S D Chernausek; C J Rosen; L R Donahue; H H Malluche; J A Fagin; T L Clemens Journal: Endocrinology Date: 2000-07 Impact factor: 4.736
Authors: Mary L Bouxsein; Clifford J Rosen; Charles H Turner; Cheryl L Ackert; Kathryn L Shultz; Leah Rae Donahue; Gary Churchill; Martin L Adamo; David R Powell; Russell T Turner; Ralph Muller; Wesley G Beamer Journal: J Bone Miner Res Date: 2002-04 Impact factor: 6.741
Authors: G Schmidmaier; B Wildemann; H Bail; M Lucke; T Fuchs; A Stemberger; A Flyvbjerg; N P Haas; M Raschke Journal: Bone Date: 2001-04 Impact factor: 4.398
Authors: Steven Boonen; Clifford Rosen; Roger Bouillon; Andreas Sommer; Malcolm McKay; David Rosen; Steven Adams; Paul Broos; Jan Lenaerts; Jef Raus; Dirk Vanderschueren; Piet Geusens Journal: J Clin Endocrinol Metab Date: 2002-04 Impact factor: 5.958
Authors: D Bikle; S Majumdar; A Laib; L Powell-Braxton; C Rosen; W Beamer; E Nauman; C Leary; B Halloran Journal: J Bone Miner Res Date: 2001-12 Impact factor: 6.741
Authors: Daniel S Perrien; Elizabeth C Brown; James Aronson; Robert A Skinner; Donna C Montague; Thomas M Badger; Charles K Lumpkin Journal: J Histochem Cytochem Date: 2002-04 Impact factor: 2.479