Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people

Hyperhomocysteinemia may contribute to the development of osteoporosis. The relationship of Hey and vitamin B-12 with bone turnover markers, BUA, and fracture incidence was studied in 1267 subjects of the Longitudinal Aging Study Amsterdam. High Hey and low vitamin B-12 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 B-12 is closely correlated to homocysteine (Hey). The main objective of our study was to examine the association of Hey and vitamin B-12 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 Hey was measured with IMx, serum vitamin B-12 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 1.995, 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 13,2 concentration, normal versus low (< 200 pM) or lowest quartile (Q1) versus normal quartiles (Q2-Q4), and Hey concentration, normal versus high (> 15 mu M) 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 Hey and vitamin B-12 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 Hey and vitamin 13,2 were separately studied in their relationship with fracture incidence. Results: Fourteen percent of the men and 9% of the women had high Hey (> 15 mu M) and low vitamin B-12 (< 200 pM) concentrations. Women with vitamin B-12 levels < 200 pM and Hey concentrations >15 mu M had lower BUA, higher DPD/Cr, and higher OC concentrations than their counterparts. In men, no differences were found between the different Hey and vitamin B-12 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 Hey and/or low vitamin B-12 concentrations was 3.8 (1.2-11.6) compared with men with normal Hey and vitamin B-12 concentrations. Women with high Hey and/or low vitamin B-12 concentrations had an adjusted RR for fractures of 2.8 (1.3-5.7). Conclusions: High Hey and low vitamin B-12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.