Multiple vitamin deficiencies additively increase the risk of incident fractures in Japanese postmenopausal women

  • T. KurodaEmail author
  • K. Uenishi
  • H. Ohta
  • M. Shiraki
Original Article



The associations of multiple vitamin deficiencies on incident fractures were uncertain, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. The number of deficiencies was additively associated with incident fracture after adjustment for possible confounding factors including the treatment of osteoporosis.


To evaluate the associations of multiple vitamin deficiencies on incident fractures, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women.


This analysis used a subset of the ongoing cohort maintained by a primary care institution. Inclusion criteria of the present study were postmenopausal women aged ≥ 50 years, without vitamin supplementation and secondary osteoporosis. Baseline serum concentrations of 25-hydroxyvitamin D (25(OH)D), undercarboxylated osteocalcin (ucOC), and homocysteine (Hcy) were measured to assess vitamin D, vitamin K, and vitamin B, respectively. Since 25(OH) D positively relates to vitamin D, ucOC and Hcy negatively relate to vitamin K and vitamin B nutrients, respectively, the subjects with lower (25(OH)D) or higher (ucOC or Hcy) values than each median value was defined as subjects with the corresponding vitamin deficiency. Subjects were divided into four groups according to the number of deficiency: no deficiency, single deficiency, double deficiencies, and triple deficiencies. Relationships between the vitamin deficiencies and incident fractures were evaluated by Cox regression analysis.


A total of 889 subjects were included in this analysis; their mean and SD age was 68.3 ± 9.5 years, and the follow-up period was 6.3 ± 5.1 years. The numbers of subjects in the four groups were 139 (15.6%), 304 (34.2%), 316 (35.5%), and 130 (14.6%) for the groups with no, single, double, and triple deficiencies, respectively. Incident fractures were observed in 264 subjects (29.7%) during the observation period. The number of deficiencies was significantly associated with incident fracture (hazard ratio 1.25, 95% confidence interval 1.04–1.50, P = 0.018) after adjustment for possible confounding factors including the treatment of osteoporosis.


Accumulation of vitamin deficiencies was related to incident fractures.


Fracture Vitamin B Vitamin D Vitamin K 



This work was partly supported by grants from the Japan Osteoporosis Foundation. We appreciate all the volunteers for contributing the clinical data and samples analyzed in this study.

Compliance with ethical standards

Conflicts of interest

H.O. received lecture fees from Pfizer. M.S. received consulting fees from Asahi Kasei Pharma and Teijin Pharma. T.K. is an employee of Asahi Kasei Corporation. K. U. and M. S. have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Public Health Research FoundationTokyoJapan
  2. 2.Division of Nutritional PhysiologyKagawa Nutrition UniversitySakado CityJapan
  3. 3.Clinical Medical Research Center, Women’s Medical Center, Sanno Medical CenterInternational University of Health and WelfareTokyoJapan
  4. 4.Department of Internal MedicineResearch Institute and Practice for Involutional DiseasesNaganoJapan

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