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Trabecular bone microstructure and local gene expression in iliac crest biopsies of men with idiopathic osteoporosis
- Source :
- Journal of Bone and Mineral Research. 26:1584-1592
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
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.
- Subjects :
- Adult
Male
musculoskeletal diseases
Pathology
medicine.medical_specialty
Biopsy
Endocrinology, Diabetes and Metabolism
Osteoporosis
Iliac crest
Metabolic bone disease
Ilium
Image Processing, Computer-Assisted
medicine
Humans
Orthopedics and Sports Medicine
Aged
biology
medicine.diagnostic_test
business.industry
Osteoid
Osteoblast
Middle Aged
medicine.disease
Radiography
medicine.anatomical_structure
Gene Expression Regulation
RANKL
Osteocalcin
biology.protein
business
Biomarkers
Densitometry
Subjects
Details
- ISSN :
- 08840431
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Journal of Bone and Mineral Research
- Accession number :
- edsair.doi.dedup.....a50add742a6e9d56152d3598f0c9b29a