Why Do Only Some Women Develop Post Menopausal Osteoporosis
Abstract
The impact of osteoporosis on individual patients and their families, health care systems, and national economies is enormous. At the onset of menopause, lack of estrogen and other sex steroids results in increased bone turnover and net bone loss. Fortunately, only 25-30% of post-menopausal women will develop vertebral fractures the hallmark of post-menopausal osteoporosis because of differences in the amount of bone lost. This proposal presents a novel theory to explain why only some women get osteoporotic fractures and proposes a first experiment to test this theory. The theory suggests a critical link between the estrogen loss, the advanced glycation endproduct (AGE) content of the bone, and signaling via the receptor for advanced glycation endproducts (RAGE) and that the combination of these three components determines the extent of bone loss post menopause. The broadly accepted ovariectomized female rat was used to model post-menopausal osteoporosis. Some of these rats were fed a special diet to induce advanced glycation endproduct formation. Their blood serum was analyzed to confirm AGE formation, bone turnover and RAGE expression. Bone morphometry was measured with microCB and histomorphometric techniques. Oseteclast expression of RAGE and co-localization with AGEs in the bone matrix was tested with immunohistochemistry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2016
- Accession Number
- AD1013336
Entities
People
- Julia Pasquale
- Marc Grynpas
- Thomas Willett
Organizations
- Mount Sinai Hospital, Toronto