Experimental hyperhomocysteinemia disturbs bone metabolism in rats

Objective. To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. Methods. Blood and urine samples were collected from rats fed with a methionine-enriched diet (HHCY, n=18) or an isocaloric control diet (control, n=10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N-terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. Results. HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2 mu mol/L; p=0.0006). Bone resorption parameters hydroxyproline (1.60 +/- 0.6 versus 0.85 +/- 0.4; p < 0.05) and N-terminal collagen I telopeptides (150.8 +/- 78 versus 48.1 +/- 26 nmol/L BCE; p < 0.05) increased, whereas bone formation marker osteocalcin (9.01 +/- 3.8 versus 15.07 +/- 4.2 ng/mL; p < 0.05) decreased in HHCY compared to control rats. The relation N-terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14 +/- 3.1 versus 4.14 +/- 1.9). BMD measurement did not reveal any differences between groups. Conclusion. These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk.