Osteoporosis International

, Volume 24, Issue 1, pp 69–76

Overweight/obesity and underweight are both risk factors for osteoporotic fractures at different sites in Japanese postmenopausal women

Original Article

Abstract

Summary

This cohort study of 1,614 postmenopausal Japanese women followed for 6.7 years showed that overweight/obesity and underweight are both risk factors for fractures at different sites. Fracture risk assessment may be improved if fracture sites are taken into account and BMI is categorized.

Introduction

The effect of body mass index (BMI) on fracture at a given level of bone mineral density (BMD) is controversial, since varying associations between BMI and fracture sites have been reported.

Methods

A total of 1,614 postmenopausal Japanese women were followed for 6.7 years in a hospital-based cohort study. Endpoints included incident vertebral, femoral neck, and long-bone fractures. Rate ratios were estimated by Poisson regression models adjusted for age, diabetes mellitus, BMD, prior fracture, back pain, and treatment by estrogen.

Results

Over a mean follow-up period of 6.7 years, a total of 254 clinical and 335 morphometric vertebral fractures, 48 femoral neck fractures, and 159 long-bone fractures were observed. Incidence rates of vertebral fracture in underweight and normal weight women were significantly lower than overweight or obese women by 0.45 (95 % confidence interval: 0.32 to 0.63) and 0.61 (0.50 to 0.74), respectively, if BMD and other risk factors were adjusted, and by 0.66 (0.48 to 0.90) and 0.70 (0.58 to 0.84) if only BMD was not adjusted. Incidence rates of femoral neck and long-bone fractures in the underweight group were higher than the overweight/obese group by 2.15 (0.73 to 6.34) and 1.51 (0.82 to 2.77) and were similar between normal weight and overweight/obesity.

Conclusions

Overweight/obesity and underweight are both risk factors for fractures at different sites. Fracture risk assessment may be improved if fracture sites are taken into account and BMI is categorized.

Keywords

Body composition Cohort study Epidemiology Obesity Osteoporosis 

Abbreviations

BAP

Bone alkaline phosphatase

BMD

Bone mineral density

BMI

Body mass index

CART

Cocaine and amphetamine-regulated transcript

eGFR

Estimated glomerular filtration rate

DXA

Dual energy x-ray absorptiometry

DM

Diabetes mellitus

FRAX

Fracture risk assessment tool

FRISC

Fracture and immobilization score

NTX

N-terminal telopeptide of type I collagen

SBP

Systolic blood pressure

SD

Standard deviation

SERM

Selective estrogen receptor modulator

ucOC

Undercarboxylated osteocalcin

VD3

Active vitamin D3

25(OH)D

25-Hydroxy-cholecalciferol

VK2

Vitamin K2

YAM

Young adult mean

References

  1. 1.
    Braithwaite RS, Col NF, Wong JB (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51:364–370PubMedCrossRefGoogle Scholar
  2. 2.
    Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk. Osteoporos Int 16:581–589PubMedCrossRefGoogle Scholar
  3. 3.
    Fujiwara S, Nakamura T, Orimo H, Hosoi T, Gorai I, Oden A, Johansson H, Kanis JA (2008) Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX). Osteoporos Int 19:429–435PubMedCrossRefGoogle Scholar
  4. 4.
    Tanaka S, Yoshimura N, Kuroda T, Hosoi T, Saito M, Shiraki M (2010) The Fracture and Immobilization Score (FRISC) for risk assessment of osteoporotic fracture and immobilization in postmenopausal women—A joint analysis of the Nagano, Miyama, and Taiji Cohorts. Bone 47(6):1064–1070PubMedCrossRefGoogle Scholar
  5. 5.
    National Osteoporosis Foundation (2008) Clinician's guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation, Washington, DC. Available at www.nof.org.
  6. 6.
    Compston J, Cooper A, Cooper C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P, Wilkins M, National Osteoporosis Guideline Group (NOGG) (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62(2):105–108PubMedCrossRefGoogle Scholar
  7. 7.
    Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182(17):1864–1873PubMedCrossRefGoogle Scholar
  8. 8.
    U.S. Preventive Services Task Force (2011) Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med 154(5):356–364Google Scholar
  9. 9.
    De Laet C, Kanis JA, Odén A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ 3rd, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16(11):1330–1338PubMedCrossRefGoogle Scholar
  10. 10.
    Armstrong ME, Spencer EA, Cairns BJ, Banks E, Pirie K, Green J, Wright FL, Reeves GK, Beral V, Million Women Study Collaborators (2011) Body mass index and physical activity in relation to the incidence of hip fracture in postmenopausal women. J Bone Miner Res 26(6):1330–1338PubMedCrossRefGoogle Scholar
  11. 11.
    Beck TJ, Petit MA, Wu G, LeBoff MS, Cauley JA, Chen Z (2009) Does obesity really make the femur stronger? BMD, geometry, and fracture incidence in the women's health initiative-observational study. J Bone Miner Res 24(8):1369–1379PubMedCrossRefGoogle Scholar
  12. 12.
    Compston JE, Watts NB, Chapurlat R, Cooper C, Boonen S, Greenspan S, Pfeilschifter J, Silverman S, Díez-Pérez A, Lindsay R, Saag KG, Netelenbos JC, Gehlbach S, Hooven FH, Flahive J, Adachi JD, Rossini M, Lacroix AZ, Roux C, Sambrook PN, Siris ES, Glow Investigators (2011) Obesity is not protective against fracture in postmenopausal women. GLOW Am J Med 124(11):1043–1050CrossRefGoogle Scholar
  13. 13.
    Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166(5):495–505PubMedCrossRefGoogle Scholar
  14. 14.
    Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24(4):702–709PubMedCrossRefGoogle Scholar
  15. 15.
    Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21(2):195–214PubMedCrossRefGoogle Scholar
  16. 16.
    von Muhlen D, Safii S, Jassal SK, Svartberg J, Barrett-Connor E (2007) Associations between the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study. Osteoporos Int 18(10):1337–1344CrossRefGoogle Scholar
  17. 17.
    Collins TC, Ewing SK, Diem SJ, Taylor BC, Orwoll ES, Cummings SR, Strotmeyer ES, Ensrud KE (2009) Peripheral arterial disease is associated with higher rates of hip bone loss and increased fracture risk in older Men. Circulation 119:2305–2312PubMedCrossRefGoogle Scholar
  18. 18.
    van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350(20):2033–2041PubMedCrossRefGoogle Scholar
  19. 19.
    Shiraki M, Kuroda T, Tanaka S, Saito M, Fukunaga M, Nakamura T (2008) Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures. J Bone Miner Metab 26(1):93–100PubMedCrossRefGoogle Scholar
  20. 20.
    Tanaka S, Kuroda T, Saito M, Shiraki M (2011) Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women. J Bone Miner Res. 2011 Jul 19, published online.Google Scholar
  21. 21.
    Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR, Resnick HE, Tylavsky FA, Black DM, Cummings SR, Harris TB, Bauer DC (2009) Health, aging, and body composition study. Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94(7):2380–2386PubMedCrossRefGoogle Scholar
  22. 22.
    Gineyts E, Munoz F, Bertholon C, Sornay-Rendu E, Chapurlat R (2010) Urinary levels of pentosidine and the risk of fracture in postmenopausal women: the OFELY study. Osteoporos Int 21(2):243–250PubMedCrossRefGoogle Scholar
  23. 23.
    Zhao LJ, Jiang H, Papasian CJ, Maulik D, Drees B, Hamilton J, Deng HW (2008) Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 23(1):17–29PubMedCrossRefGoogle Scholar
  24. 24.
    Kuroda T, Shiraki M, Tanaka S, Ohta H (2009) Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Bone 44(1):168–172PubMedCrossRefGoogle Scholar
  25. 25.
    Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H, Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19(6):331–337PubMedCrossRefGoogle Scholar
  26. 26.
    Shiraki M, Shiraki Y, Aoki C, Hosoi T, Inoue S, Kaneki M, Ouchi Y (1997) Association of bone mineral density with apolipoprotein E phenotype. J Bone Miner Res 12:1438–1445PubMedCrossRefGoogle Scholar
  27. 27.
    Kuroda T, Shiraki M, Tanaka S, Shiraki Y, Narusawa K, Nakamura T (2009) The relationship between back pain and future vertebral fracture in postmenopausal women. Spine 34:1984–1989PubMedCrossRefGoogle Scholar
  28. 28.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedCrossRefGoogle Scholar
  29. 29.
    Fukunaga M, Nakamura T, Shiraki M, Kuroda T, Ohta H, Hosoi T, Orimo H (2004) Absolute height reduction and percent height ratio of the vertebral body in incident fracture in Japanese women. J Bone Miner Metab 22:104–110PubMedCrossRefGoogle Scholar
  30. 30.
    Nielson CM, Marshall LM, Adams AL, LeBlanc ES, Cawthon PM, Ensrud K, Stefanick ML, Barrett-Connor E, Orwoll ES, Osteoporotic Fractures in Men Study Research Group (2011) BMI and fracture risk in older men: the osteoporotic fractures in men study (MrOS). J Bone Miner Res 26(3):496–502PubMedCrossRefGoogle Scholar
  31. 31.
    Prieto-Alhambra D, Premaor MO, Fina Avilés F, Hermosilla E, Martinez-Laguna D, Carbonell-Abella C, Nogués X, Compston JE, Díez-Pérez A (2011) The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res, published online.Google Scholar
  32. 32.
    Gnudi S, Sitta E, Lisi L (2009) Relationship of body mass index with main limb fragility fractures in postmenopausal women. J Bone Miner Metab 27(4):479–484PubMedCrossRefGoogle Scholar
  33. 33.
    Nevitt MC, Cummings SR, Stone KL, Palermo L, Black DM, Bauer DC, Genant HK, Hochberg MC, Ensrud KE, Hillier TA, Cauley JA (2005) Risk factors for a first-incident radiographic vertebral fracture in women > or = 65 years of age: the study of osteoporotic fractures. J Bone Miner Res 20(1):131–140PubMedCrossRefGoogle Scholar
  34. 34.
    Laslett LL, Just Nee Foley SJ, Quinn SJ, Winzenberg TM, Jones G (2012) Excess body fat is associated with higher risk of vertebral deformities in older women but not in men: a cross-sectional study. Osteoporos Int 23(1):67–74PubMedCrossRefGoogle Scholar
  35. 35.
    Pirro M, Fabbriciani G, Leli C, Callarelli L, Manfredelli MR, Fioroni C, Mannarino MR, Scarponi AM, Mannarino E (2010) High weight or body mass index increase the risk of vertebral fractures in postmenopausal osteoporotic women. J Bone Miner Metab 28(1):88–93PubMedCrossRefGoogle Scholar
  36. 36.
    Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int 17(7):1065–1077PubMedCrossRefGoogle Scholar
  37. 37.
    Ministry of Health, Labour and Welfare (2012) The National Health and Nutrition Survey in 2010. Available at http://www.mhlw.go.jp/bunya/kenkou/eiyou/h22-houkoku.html. Accessed on June 20, 2012.
  38. 38.
    Bow CH, Cheung E, Cheung CL, Xiao SM, Loong C, Soong C, Tan KC, Luckey MM, Cauley JA, Fujiwara S, Kung AW (2011) Ethnic difference of clinical vertebral fracture risk. Osteoporosis Int, published online.Google Scholar
  39. 39.
    Schett G, Kiechl S, Weger S, Pederiva A, Mayr A, Petrangeli M, Oberhollenzer F, Lorenzini R, Redlich K, Axmann R, Zwerina J, Willeit J (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166(22):2495–2501PubMedCrossRefGoogle Scholar
  40. 40.
    Siiteri PK (1987) Adipose tissue as a source of hormones. Am J Clin Nutr 45(1 Suppl):277–282PubMedGoogle Scholar
  41. 41.
    Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31(3):266–300PubMedCrossRefGoogle Scholar
  42. 42.
    Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD (2009) Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94(9):3387–3393PubMedCrossRefGoogle Scholar
  43. 43.
    Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M (2010) Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab 95(3):1247–1255PubMedCrossRefGoogle Scholar
  44. 44.
    Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K (2010) Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol (Oxf) 73(5):573–580CrossRefGoogle Scholar
  45. 45.
    Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, Barrett-Connor E, Shikany JM, Dam T, Cauley JA, Osteoporotic Fractures in Men (MrOS) Study Group (2009) Vitamin D deficiency in older men. J Clin Endocrinol Metab 94(4):1214–1222PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  1. 1.Division of Clinical Trial Design and Management, Translational Research CenterKyoto UniversityKyotoJapan
  2. 2.Public Health Research FoundationTokyoJapan
  3. 3.Department of Orthopaedic SurgeryJikei University School of MedicineTokyoJapan
  4. 4.Research Institute and Practice for Involutional DiseasesNaganoJapan

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