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Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture

Hakan Melhus, MD; Karl Michaelsson, MD; Andreas Kindmark, MD; Reinhold Bergstrom, PhD; Lars Holmberg, MD; Hans Mallmin, MD; Alicja Wolk, PhD; and Sverker Ljunghall, MD
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From University Hospital, Uppsala, Sweden; and Karolinska Institute, Stockholm, Sweden. Acknowledgments: The authors thank the study group of the Multiple Risk Survey on Swedish Women for Eating Assessment (MRS SWEA): Drs. H.-O. Adami, L. Bergkvist, A. Bruce, J. Leppert, G. Nilsson, I. Ringqvist, and B. Vessby. They also thank A. Bruce and J. Baron for valuable comments on the manuscript and B. Lundkvist, I. Nystrom, and S. Lucas for expert assistance. Requests for Reprints: Hakan Melhus, MD, Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden; e-mail, Hakan.Melhus@medicin.uu.se. Current Author Addresses: Drs. Melhus, Kindmark, and Ljunghall: Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;129(10):770-778. doi:10.7326/0003-4819-129-10-199811150-00003
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Background: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture.

Objective: To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture.

Design: A cross-sectional study and a nested case–control study.

Setting: Two counties in central Sweden.

Participants: For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case–control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66 651 women 40 to 76 years of age.

Measurements: Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review.

Results: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]).

Conclusion: High dietary intake of retinol seems to be associated with osteoporosis.





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