title: Enhanced bone morphogenetic protein-2-induced ectopic and orthotopic bone formation by intermittent parathyroid hormone (1-34) administration.
abstract: Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1-34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n = 9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1-34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1-34) resulted in significantly (p < 0.05) enhanced BMD and bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1-34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites.
authors.affiliation: Tissue Engineering and Biomaterials Laboratory, Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Diederik H R
authors.initials: DH
authors.lastname: Kempen
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hefferan
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.forename: Andras
authors.initials: A
authors.lastname: Heijink
authors.forename: Avudaiappan
authors.initials: A
authors.lastname: Maran
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D005269:Femur / Q000601:surgery; D005650:Fumarates / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011126:Polypropylenes / Q000737:chemistry; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D005650:Fumarates; D010281:Parathyroid Hormone; D011126:Polypropylenes; C097850:poly(propylene fumarate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin