Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

• Published in: Journal of bone and mineral research 2007-01, Vol.22 (1), p.127-134
• Main Authors: Gerdhem, Paul, Ivaska, Kaisa K, Isaksson, Anders, Pettersson, Kim, Väänänen, H Kalervo, Obrant, Karl J, Åkesson, Kristina
• Format: Article
• Language: English
• Subjects: Aged; aging; Biological and medical sciences; Biomarkers - blood; BMD; bone; Bone and Bones - metabolism; Bone Density; bone metabolic markers; bone ultrasound; Clinical Medicine; Female; folate; Follow-Up Studies; fracture; Fractures, Bone - epidemiology; Fundamental and applied biological sciences. Psychology; homocysteine; Homocysteine - blood; Humans; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; mortality; Orthopedics; Ortopedi; population studies; Risk Factors; Skeleton and joints; Surveys and Questionnaires; Survival Analysis; ultrasound; Vertebrates: osteoarticular system, musculoskeletal system; vitamin B-12 folate; vitamin B12
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1359/jbmr.061003

Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7‐year follow‐up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed. Introduction: Recently, the association between high serum homocysteine (Hcy) levels and an increased risk of fracture has been described. Materials and Methods: Hcy levels were measured at baseline in 996 women, all 75 years old. Vitamin B12, folate, serum cross‐linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin, urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound (QUS), and physical performance were assessed at baseline. Fractures and mortality were recorded during a mean follow‐up of 7.0 years. Results: Bone marker levels were higher in women with Hcy in the highest quartile compared with all other women (p < 0.05). The most evident correlation between Hcy and a bone marker was seen with CTX (r = 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest quartile compared with the other women (p < 0.05). During the follow‐up, 267 women sustained at least one low‐energy fracture (including 69 hip fractures). When women in the highest Hcy quartile were compared with all other women, the hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89–1.36) and for hip fracture was 1.50 (95% CI, 0.91–1.94). For the same group of women, the mortality risk was 2.16 (95% CI, 1.58–2.55). Adjustments for confounders did not substantially change these associations. Adjustment for PTH increased the HR for hip fracture to 1.67 (95% CI, 1.01–2.17). Low vitamin B12 or folate was not associated with increased fracture risk or mortality. Conclusions: High Hcy levels were associated with higher bone turnover, poor physical performance, and lower BMD. There was no clear association to fracture risk. The increased mortality among women with high Hcy levels indicates that a high Hcy level may be a marker of frailty.