title: Fracture healing in osteoporotic bone.
abstract: As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models.
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China. Electronic address: louis@ort.cuhk.edu.hk.
authors.forename: Wing Hoi
authors.initials: WH
authors.lastname: Cheung
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, Orthopaedic Trauma Institute, University of California, San Francisco/San Francisco General Hospital, San Francisco, CA94110, United States.
authors.forename: Theodore
authors.initials: T
authors.lastname: Miclau
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
authors.forename: Simon Kwoon-Ho
authors.initials: SK
authors.lastname: Chow
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, Orthopaedic Trauma Institute, University of California, San Francisco/San Francisco General Hospital, San Francisco, CA94110, United States.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Yang
authors.affiliation: Department of Trauma Surgery, Giessen University Hospital, Giessen-Marburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000473:pathology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology; D017102:Fracture Healing / Q000187:drug effects; D050723:Fractures, Bone / Q000473:pathology*; D006801:Humans; D010012:Osteogenesis; D058866:Osteoporotic Fractures / Q000473:pathology*; D010027:Osteotomy; D010052:Ovariectomy
chemical_list: D004967:Estrogens
keywords: Aging; Estrogen receptor; Fracture healing; Metaphyseal fracture; Osteoporotic bone