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  • Review Article
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Insights from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

Nature Reviews Endocrinology volume 10, pages 412–422 (2014)Cite this article

Subjects

Key Points

  • Among the fractures defined as major in FRAX® (hip, upper arm, forearm and clinical vertebral), the percentage of hip fractures is consistent across regions, but that of nonhip fractures varies substantially

  • Economic analyses most often assess spine and hip fractures, but nonvertebral, nonhip fractures are common, lead to twofold increased resource use compared with hip and spine fractures combined, and greatly affect quality of life

  • Obesity is protective against hip fractures but is associated with an increased risk of fractures of the ankle and lower leg

  • The predictive value of specific risk factors differs by skeletal sites and by risk profile for first and subsequent fractures

  • Rates of treatment with antiosteoporotic drugs fall short of guideline recommendations in women at high risk but are perhaps too frequent in women at low risk

Abstract

GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX® (upper arm, forearm, hip and clinical vertebral fractures) account for >40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.

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Figure 1: Occurrence of fractures by season.
Figure 2: Scores for health-related quality of life by fracture status and comorbid conditions at baseline.
Figure 3: Changes in scores for health-related quality of life from baseline to year 1, by type of incident fracture.
Figure 4: Total numbers of person-days spent in hospital, rehabilitation centre and nursing home for patients with spine, hip and NVNH fractures.
Figure 5: Percentages of patients with incident hip fractures in different models of predicted risk.
Figure 6: Adjusted risk of fracture by fracture site and characteristic at 3 years.
Figure 7: Predictors of use of antiosteoporosis medication in women who had incident fractures at 1 year.
Figure 8: Independent predictors of treatment failure in women with two or more incident fractures at 3 years.

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References

  1. Watts, N. B. et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis: executive summary of recommendations. Endocr. Pract. 16, 1016–1019 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Watts, N. B. Osteoporosis in men. Endocr. Pract. 19, 834–838 (2013).

    Article  PubMed  Google Scholar 

  3. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis [online], (2013).

  4. Panneman, M. J., Lips, P., Sen, S. S. & Herings, R. M. Undertreatment with anti-osteoporotic drugs after hospitalization for fracture. Osteoporos. Int. 15, 120–124 (2004).

    Article  PubMed  Google Scholar 

  5. Hooven, F., Gehlbach, S. H., Pekow, P., Bertone, E. & Benjamin, E. Follow-up treatment for osteoporosis after fracture. Osteoporos. Int. 16, 296–301 (2005).

    Article  PubMed  Google Scholar 

  6. Teng, G. G., Curtis, J. R. & Saag, K. G. Quality health care gaps in osteoporosis: how can patients, providers, and the health system do a better job? Curr. Osteoporos. Rep. 7, 27–34 (2009).

    Article  PubMed  Google Scholar 

  7. Hooven, F. H. et al. The Global Longitudinal Study of Osteoporosis in Women (GLOW): rationale and study design. Osteoporos. Int. 20, 1107–1116 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Centers for Disease Control and Prevention (CDC) & National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey 2005–2006 (US Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, MD, 2008).

  9. Brazier, J. E., Walters, S. J., Nicholl, J. P. & Kohler, B. Using the SF-36 and Euroqol on an elderly population. Qual. Life Res. 5, 195–204 (1996).

    Article  CAS  PubMed  Google Scholar 

  10. Brazier, J. E. et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ 305, 160–164 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pfeilschifter, J. et al. Regional and age-related variations in the proportions of hip fractures and major fractures among postmenopausal women: the Global Longitudinal Study of Osteoporosis in Women. Osteoporos. Int. 23, 2179–2188 (2012).

    Article  CAS  PubMed  Google Scholar 

  12. Kanis, J. A. on behalf of the WHO Scientific Group. Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre for Metabolic Bone Diseases (University of Sheffield, 2007).

  13. Scholes, S. et al. Epidemiology of lifetime fracture prevalence in England: a population study of adults aged 55 years and over. Age Ageing 43, 234–240 (2014).

    Article  PubMed  Google Scholar 

  14. Amin, S., Achenbach, S. J., Atkinson, E. J., Khosla, S. & Melton, L. J. 3rd. Trends in fracture incidence: a population-based study over 20 years. J. Bone Miner. Res. 29, 581–589 (2014).

    Article  PubMed  Google Scholar 

  15. Crisp, A. et al. Declining incidence of osteoporotic hip fracture in Australia. Arch. Osteoporos. 7, 179–185 (2012).

    Article  PubMed  Google Scholar 

  16. Lam, A. et al. Major osteoporotic to hip fracture ratios in Canadian men and women with Swedish comparisons: a population based analysis. J. Bone Miner. Res. http://dx.doi.org/10.1002/jbmr.2146.

  17. Ettinger, B., Black, D. M., Dawson-Hughes, B., Pressman, A. R. & Melton, L. J. 3rd. Updated fracture incidence rates for the US version of FRAX. Osteoporos Int. 21, 25–33 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Kanis, J. A. et al. Long-term risk of osteoporotic fracture in Malmö. Osteoporos. Int. 11, 669–674 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Leslie, W. D. et al. Secular decreases in fracture rates 1986–2006 for Manitoba, Canada: a population-based analysis. Osteoporos. Int. 22, 2137–2143 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Gronskag, A. B., Forsmo, S., Romundstad, P., Langhammer, A. & Schei, B. Incidence and seasonal variation in hip fracture incidence among elderly women in Norway. The HUNT Study. Bone 46, 1294–1298 (2010).

    Article  PubMed  Google Scholar 

  21. Emaus, N. et al. Hip fractures in a city in Northern Norway over 15 years: time trends, seasonal variation and mortality: the Harstad Injury Prevention Study. Osteoporos. Int. 22, 2603–2610 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lofthus, C. M. et al. Epidemiology of hip fractures in Oslo, Norway. Bone 29, 413–418 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Rogmark, C., Sernbo, I., Johnell, O. & Nilsson, J. A. Incidence of hip fractures in Malmo, Sweden, 1992–1995. A trend-break. Acta Orthop. Scand. 70, 19–22 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Jacobsen, S. J. et al. Seasonal variation in the incidence of hip fracture among white persons aged 65 years and older in the United States, 1984–1987. Am. J. Epidemiol. 133, 996–1004 (1991).

    Article  CAS  PubMed  Google Scholar 

  25. Bischoff-Ferrari, H. A., Orav, J. E., Barrett, J. A. & Baron, J. A. Effect of seasonality and weather on fracture risk in individuals 65 years and older. Osteoporos. Int. 18, 1225–1233 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Levy, A. R., Bensimon, D. R., Mayo, N. E. & Leighton, H. G. Inclement weather and the risk of hip fracture. Epidemiology 9, 172–177 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Giladi, A. M. et al. Variation in the incidence of distal radius fractures in the US elderly as related to slippery weather conditions. Plast. Reconstr. Surg. 133, 321–332 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Modarres, R., Ouarda, T. B., Vanasse, A., Orzanco, M. G. & Gosselin, P. Modeling seasonal variation of hip fracture in Montreal, Canada. Bone 50, 909–916 (2012).

    Article  PubMed  Google Scholar 

  29. Øyen, J., Rhode, G. E., Hochberg, M., Johnsen, V. & Haugeberg, G. Low-energy distal radius fractures in middle-aged and elderly women—seasonal variations, prevalence of osteoporosis, and associates with fractures. Osteoporos. Int. 21, 1247–1255 (2010).

    Article  PubMed  Google Scholar 

  30. Iolascon, G., Gravina, P., Luciano, F., Palladino, C. & Gimigliano, F. Characteristics and circumstances of falls in hip fractures. Aging Clin. Exp. Res. 25 (Suppl. 1), S133–S135 (2013).

    Article  PubMed  Google Scholar 

  31. Costa, E. et al. When, where and how osteoporosis-associated fractures occur: an analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW). PLoS ONE 8, e83306 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Arakaki, H. et al. Epidemiology of hip fractures in Okinawa, Japan. J. Bone Miner. Metab. 29, 309–314 (2011).

    Article  PubMed  Google Scholar 

  33. Karantana, A. et al. Epidemiology and outcome of fracture of the hip in women aged 65 years and under: a cohort study. J. Bone Joint Surg. Br. 93, 658–664 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Bischoff-Ferrari, H. A. The role of falls in fracture prediction. Curr. Osteoporos. Rep. 9, 116–121 (2011).

    Article  PubMed  Google Scholar 

  35. Nevitt, M. C., Cummings, S. R. & The Study of Osteoporotic Fractures Research Group. Type of fall and risk of hip and wrist fractures: the study of osteoporotic fractures. J. Am. Geriatr. Soc. 41, 1226–1234 (1993).

    Article  CAS  PubMed  Google Scholar 

  36. Morrison, A., Fan, T., Sen, S. S. & Weisenfluh, L. Epidemiology of falls and osteoporotic fractures: a systematic review. Clinicoecon. Outcomes Res. 5, 9–18 (2013).

    PubMed  Google Scholar 

  37. Adachi, J. D. et al. Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. Mayo Clin. Proc. 85, 806–813 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Roux, C. et al. Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW). Osteoporos. Int. 23, 2863–2871 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ioannidis, G. et al. Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW). Osteoporos. Int. 24, 59–67 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Compston, J. E. et al. Obesity, health-care utilization, and health-related quality of life after fracture in postmenopausal women: Global Longitudinal Study of Osteoporosis in Women (GLOW). Calc. Tissue Int. 94, 223–231 (2014).

    Article  CAS  Google Scholar 

  41. Díez-Pérez, A. et al. Regional differences in treatment for osteoporosis. The Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone 49, 493–498 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Guggina, P. et al. Characteristics associated with anti-osteoporosis medication use: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) USA cohort. Bone 51, 975–980 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Siris, E. S. et al. Failure to perceive increased risk of fracture in women 55 years and older: the Global Longitudinal Study of Osteoporosis in Women (GLOW). Osteoporos. Int. 22, 27–35 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Tom, S. E. et al. Frailty and fracture, disability, and falls: a multiple country study from the global longitudinal study of osteoporosis in women. J. Am. Geriatr Soc. 61, 327–334 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Greenspan, S. L. et al. Predictors of treatment with osteoporosis medications after recent fragility fractures in a multinational cohort of postmenopausal women. J. Am. Geriatr Soc. 60, 455–461 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Compston, J. E. et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am. J. Med. 124, 1043–1050 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sambrook, P. N. et al. Predicting fractures in an international cohort using risk factor algorithms without BMD. J. Bone Miner. Res. 26, 2770–2777 (2011).

    Article  PubMed  Google Scholar 

  48. Compston, J. E. et al. Relationship of weight, height, and body mass index with fracture risk at different sites in postmenopausal women: The global longitudinal study of osteoporosis in women (GLOW). J. Bone Miner. Res. 29, 487–493 (2014).

    Article  PubMed  Google Scholar 

  49. Díez-Pérez, A. et al. Risk factors for treatment failure with antiosteoporosis medication: The global longitudinal study of osteoporosis in women (GLOW). J. Bone Miner. Res. 29, 260–267 (2014).

    Article  PubMed  Google Scholar 

  50. FitzGerald, G. et al. Differing risk profiles for individual fracture sites: evidence from the Global Longitudinal Study of Osteoporosis in Women (GLOW). J. Bone Miner. Res. 27, 1907–1915 (2012).

    Article  PubMed  Google Scholar 

  51. Gregson, C. L. et al. Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study. Osteoporos. Int. 25, 85–95 (2014).

    Article  CAS  PubMed  Google Scholar 

  52. Adachi, J. D. et al. Fracture patterns with use of selective serotonin receptor inhibitors, proton pump inhibitors and glucocorticoids in a large international observational study. Presented at the ASBMR 2013 Annual Meeting [abstract 1049].

  53. Warriner, A. et al. Osteoporosis medication adherence: reasons for stopping and not starting. Presented at ACR/ARHP Annual Meeting 13 [abstract 1243].

  54. Gehlbach, S. et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J. Bone Miner. Res. 27, 645–653 (2012).

    Article  PubMed  Google Scholar 

  55. Stone, K. L. et al. BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J. Bone Miner. Res. 18, 1947–1954 (2003).

    Article  PubMed  Google Scholar 

  56. van Staa, T. P., Leufkens, H. G. & Cooper, C. Does a fracture at one site predict later fractures at other sites? A British cohort study. Osteoporos. Int. 13, 624–629 (2002).

    Article  CAS  PubMed  Google Scholar 

  57. Dennison, E. M. et al. Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone 50, 1288–1293 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Prieto-Alhambra, D. et al. An increased rate of falling leads to a rise in fracture risk in postmenopausal women with self-reported osteoarthritis: a prospective multinational cohort study (GLOW). Ann. Rheum. Dis. 72, 911–917 (2013).

    Article  PubMed  Google Scholar 

  59. Fried, L. P. et al. Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146–M156 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Tang, X. et al. Obesity and risk of hip fracture in adults: a meta-analysis of prospective cohort studies. PLoS ONE 12, e55077 (2013).

    Article  Google Scholar 

  61. Nielson, C. M., Srikanth, P. & Orwoll, E. S. Obesity and fracture in men and women: an epidemiologic perspective. J. Bone Miner. Res. 27, 1–10 (2012).

    Article  PubMed  Google Scholar 

  62. Beck, T. J. et al. 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, 1369–1379 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Garvan Institute. Fracture risk calculator [online].

  64. Ohman, E. M., Granger, C. B., Harrington, R. A. & Lee, K. L. Risk stratification and therapeutic decision making in acute coronary syndromes. JAMA 284, 876–878 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Harrell, F. E. Jr, Califf, R. M., Pryor, D. B., Lee, K. L. & Rosati, R. A. Evaluating the yield of medical tests. JAMA 247, 2543–2546 (1982).

    Article  PubMed  Google Scholar 

  66. Chen, J. S., Hogan, C., Lyubomirsky, G. & Sambrook, P. N. Women with cardiovascular disease have increased risk of osteoporotic fracture. Calcif. Tissue Int. 88, 9–15 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Drake, M. T. et al. Clinical review. Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 97, 1861–1870 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Janghorbani, M., Van Dam, R. M., Willett, W. C. & Hu, F. B. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am. J. Epidemiol. 166, 495–505 (2007).

    Article  PubMed  Google Scholar 

  69. Vestergaard, P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos. Int. 18, 427–444 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Loke, Y. K., Cavallazzi, R. & Singh, S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax 66, 699–708 (2011).

    Article  PubMed  Google Scholar 

  71. David, C. et al. Severity of osteoporosis: what is the impact of co-morbidities? Joint Bone Spine 77 (Suppl. 2), S103–S106 (2010).

    Article  PubMed  Google Scholar 

  72. Bazelier, M. T. et al. Risk of fractures in patients with multiple sclerosis: a population-based cohort study. Neurology 78, 1967–1973 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The GLOW study was supported by the Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis), the Warner Chilcott Company and Sanofi-Aventis. We thank S. Rushton-Smith for coordinating revisions and providing editorial assistance, including editing, checking content and language, formatting and referencing, A. Wyman for checking the statistical findings and editing the tables, figures and results, and G. FitzGerald, E. Siris and J. Compston for reviewing manuscript sections.

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  1. Mercy Health Osteoporosis and Bone Health Services, 4760 E. Galbraith Road, Suite 212, Cincinnati, 45236, OH, USA

    Nelson B. Watts

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Correspondence to Nelson B. Watts.

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Competing interests

N.B.W. is co-founder, stockholder and director of OsteoDynamics; has received honoraria for lectures from Amgen and Merck in the past year; has received consulting fees from AbbVie, Amarin, Amgen, Bristol–Myers Squibb, Corcept, Endo, Imagepace, Janssen, Lilly, Merck, Novartis, Noven, Pfizer/Wyeth, Radius and Sanofi-Aventis in the past year; and, through his Health System, has received research support from Merck and NPS Pharmaceuticals.

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Watts, N. Insights from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Nat Rev Endocrinol 10, 412–422 (2014). https://doi.org/10.1038/nrendo.2014.55

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