Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study.

CONTEXT The association between retinol and bone mineral density (BMD) in males after puberty has not been fully investigated previously. OBJECTIVE To investigate the association between retinol, retinol-binding protein-4 (RBP-4), BMD (g/cm(2)), abdominal fat mass, and markers of bone metabolism in young men. DESIGN Longitudinal study. PARTICIPANTS Seventy-eight healthy males with a mean age of 22.6+/-0.7 years at baseline. A follow-up was conducted in 73 of the participants 2.0+/-0.4 years later. MAIN OUTCOME MEASURES Associations between serum concentrations of retinol and RBP-4, and BMD of the total body, lumbar spine, and hip, serum concentrations of osteocalcin, and carboxy terminal telopeptide of type 1 collagen (CTX), were investigated. RESULTS Both retinol and RBP-4 showed an inverse relationship with that of osteocalcin (r=-0.23 to -0.25, P<0.05). Levels of RBP-4 (r=0.26, P=0.02) and osteocalcin (r=-0.23, P=0.04) were also related to abdominal fat mass, and the relationship between RBP-4, retinol, and osteocalcin disappeared after adjusting for this influence of abdominal fat mass. Neither retinol nor RBP-4 concentrations were associated with BMD at any site, CTX as baseline, or changes in BMD during the 2-year follow-up period. Levels of RBP-4 showed a strong association with levels of retinol (r=0.61, P<0.001). CONCLUSION We found a negative association between the bone formation marker osteocalcin with retinol and RBP-4. The association disappeared when adjusting for the influence of abdominal fat mass. Neither retinol nor RBP-4 were associated with peak BMD in young men.

[1]  R. Eastell,et al.  Measurement of Osteocalcin , 2000, Annals of clinical biochemistry.

[2]  A. Parfitt The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis. , 1982, Metabolic bone disease & related research.

[3]  H. DeLuca,et al.  Vitamin A antagonizes the action of vitamin D in rats. , 1999, The Journal of nutrition.

[4]  M. V. van’t Hof,et al.  Reference values for plasma concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted for seasonal influences. , 1997, Clinical chemistry.

[5]  H. Melhus,et al.  Vitamin A Antagonizes Calcium Response to Vitamin D in Man , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  P. Delmas,et al.  Biochemical Measurements of Bone Turnover in Children and Adolescents , 2000, Osteoporosis International.

[7]  P. Galan,et al.  Vitamin status of a healthy French population: dietary intakes and biochemical markers. , 1994, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[8]  M. Seshadri,et al.  Hypervitaminosis A and calcium-regulating hormones in the rat. , 1986, The Journal of nutrition.

[9]  C. Slemenda,et al.  The contribution of bone loss to postmenopausal osteoporosis , 1990, Osteoporosis International.

[10]  S. Kelder,et al.  Longitudinal tracking of adolescent smoking, physical activity, and food choice behaviors. , 1994, American journal of public health.

[11]  L. Holmberg,et al.  Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture , 1998, Annals of Internal Medicine.

[12]  H. Hassan,et al.  Retinoic acid suppresses interleukin 6 production in normal human osteoblasts. , 2000, Cytokine.

[13]  M. Wahlqvist,et al.  Dietary carotenoid intake as a predictor of bone mineral density. , 2003, Asia Pacific journal of clinical nutrition.

[14]  K. Michaëlsson,et al.  Serum retinol levels and the risk of fracture. , 2003, The New England journal of medicine.

[15]  N. Lien,et al.  Stability in consumption of fruit, vegetables, and sugary foods in a cohort from age 14 to age 21. , 2001, Preventive medicine.

[16]  E. Barrett-Connor,et al.  Retinol Intake and Bone Mineral Density in the Elderly: The Rancho Bernardo Study , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  J. Bilezikian,et al.  Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study. , 2004, The American journal of medicine.

[18]  C. Johnson,et al.  Serum retinol levels of persons aged 4-74 years from three Hispanic groups. , 1988, The American journal of clinical nutrition.

[19]  D. C. Bauer,et al.  Clinical Use of Biochemical Markers of Bone Remodeling: Current Status and Future Directions , 2000, Osteoporosis International.

[20]  M. Sowers,et al.  Retinol, supplemental vitamin A and bone status. , 1990, Journal of clinical epidemiology.

[21]  John J. B. Anderson Oversupplementation of Vitamin A and Osteoporotic Fractures in the Elderly: To Supplement or Not to Supplement With Vitamin A , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  S. Teitelbaum,et al.  Effects of hypervitaminosis A on the bone and mineral metabolism of the rat. , 1988, Endocrinology.

[23]  D. Reid,et al.  Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. , 2004, The American journal of clinical nutrition.

[24]  D. Galuska,et al.  High Serum Retinyl Esters Are Not Associated with Reduced Bone Mineral Density in the Third National Health and Nutrition Examination Survey, 1988–1994 , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  N. Binkley,et al.  Hypervitaminosis A and bone. , 2009, Nutrition reviews.

[26]  M. Barker,et al.  Serum Retinoids and β‐Carotene as Predictors of Hip and Other Fractures in Elderly Women , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  B. Bowman,et al.  Serum retinol distributions in residents of the United States: third National Health and Nutrition Examination Survey, 1988-1994. , 2001, The American journal of clinical nutrition.

[28]  M. Seibel,et al.  Molecular Markers of Bone Turnover: Biochemical, Technical and Analytical Aspects , 2000, Osteoporosis International.

[29]  M. Polidori,et al.  Low levels of carotenoids and retinol in involutional osteoporosis. , 2006, Bone.

[30]  P. Fottrell,et al.  Osteocalcin: diagnostic methods and clinical applications. , 1991, Critical reviews in clinical laboratory sciences.

[31]  A. Nordström,et al.  Relationship between Vitamin D Metabolites and Bone Mineral Density in Young Males: A Cross-Sectional and Longitudinal Study , 2006, Calcified Tissue International.

[32]  U. Smith,et al.  Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. , 2006, The New England journal of medicine.

[33]  F. Granado,et al.  Reference values for retinol, tocopherol, and main carotenoids in serum of control and insulin-dependent diabetic Spanish subjects. , 1997, Clinical chemistry.

[34]  M. Neovius,et al.  Early and rapid bone mineral density loss of the proximal femur in men. , 2007, The Journal of clinical endocrinology and metabolism.

[35]  R. Rizzoli,et al.  Peak bone mass , 2005, Osteoporosis International.

[36]  W. Willett,et al.  Vitamin A intake and hip fractures among postmenopausal women. , 2002, JAMA.

[37]  M. McKee,et al.  Endocrine Regulation of Energy Metabolism by the Skeleton , 2007, Cell.