title: Influence of factors regulating bone formation and remodeling on bone quality in osteonecrosis of the femoral head.
abstract: Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.
authors.affiliation: Department of Orthopedic Surgery, University of Regensburg, Kaiser-Karl V-Allee 3, 93077 Bad Abbach, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tingart
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckmann
authors.forename: Alfred
authors.initials: A
authors.lastname: Opolka
authors.forename: Maiko
authors.initials: M
authors.lastname: Matsuura
authors.forename: Oliver
authors.initials: O
authors.lastname: Wiech
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
mesh_terms: D000328:Adult; D000368:Aged; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D016022:Case-Control Studies; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005260:Female; D005270:Femur Head / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D010020:Osteonecrosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D015675:Osteocalcin