title: BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats.
abstract: Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats.
authors.affiliation: Department of Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands. T.J.Blokhuis@umcutrecht.nl
authors.forename: T J
authors.initials: TJ
authors.lastname: Blokhuis
authors.forename: P
authors.initials: P
authors.lastname: Buma
authors.forename: N
authors.initials: N
authors.lastname: Verdonschot
authors.forename: M
authors.initials: M
authors.lastname: Gotthardt
authors.forename: T
authors.initials: T
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology* / Q000627:therapeutic use; D002146:Bony Callus / Q000473:pathology; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar
chemical_list: D050071:Bone Density Conservation Agents; D055419:Bone Morphogenetic Protein 7; D004164:Diphosphonates; D004967:Estrogens