title: Trabecular bone microstructure and local gene expression in iliac crest biopsies of men with idiopathic osteoporosis.
abstract: Male idiopathic osteoporosis (MIO) is a metabolic bone disease that is characterized by low bone mass, microstructural alterations, and increased fracture risk in otherwise healthy men. Although the detailed pathophysiology of MIO has yet to be clarified, evidence increasingly suggests an osteoblastic defect as the underlying cause. In this study we tested the hypothesis that the expression profile of certain osteoblastic or osteoblast-related genes (ie, WNT10B, RUNX2, Osterix, Osteocalcin, SOST, RANKL, and OPG) is different in iliac crest biopsies of MIO patients when compared with healthy controls. Furthermore, we investigated the relation of local gene expression characteristics with histomorphometric, microstructural, and clinical features. Following written informed consent and diligent clinical patient characterization, iliac crest biopsies were performed in nine men. While RNA extraction, reverse-transcription, and real-time polymerase chain reactions (PCRs) were performed on one biopsy, a second biopsy of each patient was submitted for histomorphometry and micro-computed tomography (µCT). Age-matched bone samples from forensic autopsies served as controls. MIO patients displayed significantly reduced WNT10B, RUNX2, RANKL, and SOST expression. Performing µCT for the first time in MIO biopsies, we found significant decreases in trabecular number and connectivity density. Trabecular separation was increased significantly, but trabecular thickness was similar in both groups. Histomorphometry revealed decreased BV/TV and osteoid volume and fewer osteoclasts in MIO. By providing evidence for reduced local WNT10B, RUNX2, and RANKL gene expression and histomorphometric low turnover, our data support the osteoblast dysfunction model discussed for MIO. Further, MIO seems to lead to a different microstructural pathology than age-related bone loss.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Immunology and Infectiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Patsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Kohler
authors.forename: Andrea
authors.initials: A
authors.lastname: Berzlanovich
authors.forename: Christian
authors.initials: C
authors.lastname: Muschitz
authors.forename: Christian
authors.initials: C
authors.lastname: Bieglmayr
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Heinrich
authors.initials: H
authors.lastname: Resch
authors.forename: Peter
authors.initials: P
authors.lastname: Pietschmann
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003720:Densitometry; D005786:Gene Expression Regulation; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D011859:Radiography
chemical_list: D015415:Biomarkers