Is hyperhomocysteinemia a risk factor for osteoporosis?

Abstract

Hyperhomocysteinemia (HHCY) has been accepted as a risk factor not only for cardiovascular diseases (CVDs) but also for osteoporosis. Furthermore, clinical data suggest that HHCY also increases fracture risk, but have no or only minor effects on bone mineral density (BMD). Measurement of biochemical bone turnover markers indicates a shift of bone metabolism toward bone resorption. Animal studies confirm these observations showing a reduced bone quality and stimulation of bone resorption in hyperhomocysteinemic animals. In addition, homocysteine (HCY) has been found to accumulate in bone tissue by collagen binding. These results indicate a causal involvement of HHCY in osteoporosis. The first experimental studies revealed that several pathomechanisms might be involved. Cell culture studies demonstrate that high HCY and low vitamin B levels stimulate osteoclasts but not osteoblasts, indicating again a shift of bone metabolism toward bone resorption. In addition, HHCY seems to have adverse affects on extracellular bone matrix by disturbing collagen crosslinking. Well-performed large cell culture studies confirm the results obtained with exogenous HCY administration. In conclusion, existing data suggest that HHCY (and possibly vitamin B deficiencies) adversely affects bone quality by a stimulation of bone resorption and disturbance of collagen crosslinking.