{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:33:43Z","timestamp":1791102823706,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>Results: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I\u2013treated 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\u2013treated groups.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1359\/jbmr.060618","type":"journal-article","created":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T04:29:34Z","timestamp":1156912174000},"page":"1359-1366","source":"Crossref","is-referenced-by-count":55,"title":["Effects of Systemic and Local Administration of Recombinant Human IGF-I (rhIGF-I) on De Novo Bone Formation in an Aged Mouse Model"],"prefix":"10.1093","volume":"21","author":[{"given":"John L","family":"Fowlkes","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn 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