Homocysteine and Vitamin B12 Status Relate to Bone Turnover Markers, Broadband Ultrasound Attenuation, and Fractures in Healthy Elderly People

Abstract

Hyperhomocysteinemia may contribute to the development of osteoporosis. The relationship of Hcy and vitamin B₁₂ with bone turnover markers, BUA, and fracture incidence was studied in 1267 subjects of the Longitudinal Aging Study Amsterdam. High Hcy and low vitamin B₁₂ concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk. Introduction: Hyperhomocysteinemia may contribute to the development of osteoporosis. Vitamin B₁₂ is closely correlated to homocysteine (Hcy). The main objective of our study was to examine the association of Hcy and vitamin B₁₂ status and the combined effect of these two with broadband ultrasound attenuation (BUA), bone turnover markers, and fracture. Materials and Methods: Subjects were 615 men and 652 women with a mean age of 76 ± 6.6 (SD) years of the Longitudinal Aging Study Amsterdam (LASA). At baseline (1995/1996), blood samples were taken after an overnight fast for dairy products. Plasma Hcy was measured with IMx, serum vitamin B₁₂ with competitive immunoassay (IA) luminescence, serum osteocalcin (OC) with immunoradiometric assay (IRMA), and urinary excretion of deoxypyridinoline (DPD) with competitive IA and corrected for creatinine (Cr) concentration. CVs were 4%, 5%, 8%, and 5%, respectively. BUA was assessed in the heel bone twice in both the right and left calcaneus. Mean BUA value was calculated from these four measurements. CV was 3.4%. After baseline measurements in 1995, a 3‐year prospective follow‐up of fractures was carried out until 1998/1999. Subjects were grouped by using two different approaches on the basis of their vitamin B₁₂ concentration, normal versus low (15 μM) or highest quartile (Q4) versus normal quartiles (Q1‐Q3). Analysis of covariance was performed to calculate mean values of BUA, OC, and DPD/Cr_urine based on the specified categories of Hcy and vitamin B₁₂ and adjusted for several confounders (potential confounders were age, sex, body weight, body height, current smoking [yes/no], mobility, cognition). The relative risk (RR) of any fracture was assessed with Cox regression analysis. Quartiles were used when Hcy and vitamin B₁₂ were separately studied in their relationship with fracture incidence. Results: Fourteen percent of the men and 9% of the women had high Hcy (>15 μM) and low vitamin B₁₂ (12 levels 15 μM had lower BUA, higher DPD/Cr, and higher OC concentrations than their counterparts. In men, no differences were found between the different Hcy and vitamin B₁₂ categories in adjusted means of BUA, OC, or DPD/Cr_urine. Twenty‐eight men and 43 women sustained a fracture during the 3‐year follow‐up period. The adjusted RR for fractures (95% CI) for men with high Hcy and/or low vitamin B₁₂ concentrations was 3.8 (1.2‐11.6) compared with men with normal Hcy and vitamin B₁₂ concentrations. Women with high Hcy and/or low vitamin B₁₂ concentrations had an adjusted RR for fractures of 2.8 (1.3‐5.7). Conclusions: High Hcy and low vitamin B₁₂ concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.