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Menstrual and reproductive factors and risk of vertebral fractures in Japanese women: the Japan Public Health Center-based prospective (JPHC) study

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Abstract

Summary

This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism.

Introduction

This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women.

Methods

Participants were 43,652 women aged 40–69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors.

Results

During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24–3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01–2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92–0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51–3.73) in all women, 2.25 (1.35–3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499).

Conclusions

Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.

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Acknowledgements

We wish to thank all staff members in each study area and in the central offices for their cooperation and technical assistance. We are particularly grateful for the helpful statistical advice of Dr. Hadrien Charvat. Members of the Japan Public Health Center-based prospective study (JPHC Study, principal investigator: S. Tsugane) group are listed at the following site (as of April 2017): http://epi.ncc.go.jp/en/jphc/781/7951.html.

Funding

This study was supported by a National Cancer Center Research and Development Fund (since 2011), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010), and a Grant-in-Aid for AMED-Wise, a project for whole implementation to support and ensure the female life, from Japan Agency for Medical Research and Development, AMED.

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Authors and Affiliations

  1. Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Y. Shimizu, N. Sawada, M. Iwasaki & S. Tsugane

  2. Department of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    K. Nakamura, Y. Watanabe & K. Kitamura

Authors
  1. Y. Shimizu
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  2. N. Sawada
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  3. K. Nakamura
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  4. Y. Watanabe
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  5. K. Kitamura
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  6. M. Iwasaki
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  7. S. Tsugane
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For the JPHC Study group

Corresponding author

Correspondence to N. Sawada.

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Human and animal rights and informed consent

The study was conducted in accordance with the declaration of Helsinki, informed consent was obtained from all individual participants, and the study protocol was approved by the Institutional Review Board of the National Cancer Center, Tokyo, Japan.

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Shimizu, Y., Sawada, N., Nakamura, K. et al. Menstrual and reproductive factors and risk of vertebral fractures in Japanese women: the Japan Public Health Center-based prospective (JPHC) study. Osteoporos Int 29, 2791–2801 (2018). https://doi.org/10.1007/s00198-018-4665-8

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