Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: The Rotterdam Study Nahid Yazdanpanah a,b,c , M. Carola Zillikens a , Fernando Rivadeneira a,c , Robert de Jong b , Jan Lindemans b , André G. Uitterlinden a,b,c , Huibert A.P. Pols a,c , Joyce B.J. van Meurs a, ⁎ a Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands b Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands c Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands Received 16 May 2007; revised 26 July 2007; accepted 4 August 2007 Available online 17 August 2007 Abstract A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians. We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine (β = 0.09, p =1×10 - 8 ) and riboflavin intake (β = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy- adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65–0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40–0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results. We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures. © 2007 Elsevier Inc. All rights reserved. Keywords: Osteoporosis; Bone mineral density; Fracture; Pyridoxine; Dietary B vitamins Introduction Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an in- creased risk of fracture. Several risk factors have been identified for osteoporotic fracture, such as age, low body mass index (BMI) and low bone mineral density (BMD). More recently, mildly elevated homocysteine (Hcy) concentrations were iden- tified as a novel and potentially modifiable risk factor for age- related osteoporotic fractures [1,2]. Hcy is a sulfur-containing amino acid formed from the es- sential amino acid methionine. Defects in intracellular Hcy metabolism lead to an elevation of plasma Hcy concentrations. These metabolic defects can have a genetic cause, i.e., polymorphisms in genes involved in the Hcy metabolism. On the other hand, defects in the Hcy metabolism can also have a nutritional cause, such as inadequate intake of folate (vitamin B 11 ), riboflavin (vitamin B 2 ), pyridoxine (vitamin B 6 ) or cobalamin (vitamin B 12 ) which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism [3,4]. It is well Bone 41 (2007) 987 – 994 www.elsevier.com/locate/bone ⁎ Corresponding author. Room Ee 571, Genetic Laboratory, Department of Internal Medicine, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Fax: +31 10 4635430. E-mail address: j.vanmeurs@erasmusmc.nl (J.B.J. van Meurs). 8756-3282/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.bone.2007.08.021