Aspects of bone quality in osteoporosis and osteoarthritis : collagen post-translational modification and mechanical factors
Osteoporosis and osteoarthritis represent major public health problems in the developed world. In both disorders there is accumulating evidence to suggest that alterations in the organic component of bone matrix may play a role in the progression of these diseases. A comparative analysis of aspects of the organic bone matrix was undertaken in order to determine if bone quality was altered in either of these diseases. The early posttranslational modifications and subsequent covalent cross-linking profile of type I collagen of bone were measured, along with the matrix content of transforming growth factor beta, TGF, a locally produced factor known to enhance bone formation in vivo. No association was found between levels of collagen lysyl-hydroxylation, glycosylation of hydroxylated lysines, and the levels of both the reduced divalent crosslinks dihydroxylysinonorleucine and hydroxylysinonorleucine, and the mature trivalent pyridinium crosslinks in any of the study groups. Changes in the organic bone matrix were found to be more profound in females compared with males regardless of disease state. Female osteoporotic subjects had significantly higher levels of both forms of the divalent crosslinks, and significantly lower levels of lysyl-hydroxylation compared with their sex-matched counterparts in the normal reference group. Females from both the osteoporotic and osteoarthritic study groups had significantly higher TGF content compared with the normal reference group. These data point towards the possibility that post-menopausal oestrogen withdrawal may result in altered bone quality in the aged female skeleton. In order to investigate the possible effects of mechanical loading on the composition of bone matrix produced, a novel in vitro loading system was designed and constructed. The new system allows the controlled application of defined, cyclic, physiological strains to primary osteoblast cell cultures, facilitating investigation into mechanical loading and control of bone matrix composition.