Impact of Hip Fracture on Mortality: A Cohort Study in Hip Fracture Discordant Identical Twins

Several studies have shown a long‐lasting higher mortality after hip fracture, but the reasons for the excess risk are not well understood. We aimed to determine whether a higher mortality after hip fracture exists when controlling for genetic constitution, shared environment, comorbidity, and lifestyle by use of a nationwide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972 to 2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable‐adjusted hazard ratios (HRs) for death. During follow‐up, 143 twins with a hip fracture died (50%) compared with 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased fourfold in women (HR = 3.71; 95% confidence interval [CI] 1.32–10.40) and sevenfold in men (HR = 6.67; 95% CI 1.47–30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year = 0.99; 95% CI 0.66–1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02–6.62). The higher risk in men after the hip fracture event was successively attenuated during follow‐up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29–4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06–1.7) and 2.7 years in men (95% CI 1.7–3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31–61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity, and lifestyle. © 2014 American Society for Bone and Mineral Research.

[1]  K. Michaëlsson,et al.  Genetic influence on bone phenotypes and body composition: a Swedish twin study , 2013, Journal of Bone and Mineral Metabolism.

[2]  P. Lichtenstein,et al.  Twinship influence on morbidity and mortality across the lifespan. , 2012, International journal of epidemiology.

[3]  P. Tang,et al.  Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. , 2012, Injury.

[4]  R. Krueger,et al.  Genes, environments, personality, and successful aging: toward a comprehensive developmental model in later life. , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  J. Vaupel,et al.  Skewed X inactivation and survival: a 13-year follow-up study of elderly twins and singletons , 2011, European Journal of Human Genetics.

[6]  D. Richardson,et al.  Sex differences in telomeres and lifespan , 2011, Aging cell.

[7]  Consuelo Borras,et al.  Females live longer than males: role of oxidative stress. , 2011, Current pharmaceutical design.

[8]  Howard A Fink,et al.  Hip fracture and increased short-term but not long-term mortality in healthy older women. , 2011, Archives of internal medicine.

[9]  Paul C. Lambert,et al.  Flexible Parametric Survival Analysis Using Stata: Beyond the Cox Model , 2011 .

[10]  R. Sterling Gender and Race/Ethnicity Differences in Hip Fracture Incidence, Morbidity, Mortality, and Function , 2011, Clinical orthopaedics and related research.

[11]  J. Ludvigsson,et al.  External review and validation of the Swedish national inpatient register , 2011, BMC public health.

[12]  M. Shammas Telomeres, lifestyle, cancer, and aging , 2011, Current opinion in clinical nutrition and metabolic care.

[13]  Kaare Christensen,et al.  Causal Inference and Observational Research , 2010, Perspectives on psychological science : a journal of the Association for Psychological Science.

[14]  S. Manolagas From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. , 2010, Endocrine reviews.

[15]  A. Parfitt,et al.  What old means to bone , 2010, Trends in Endocrinology & Metabolism.

[16]  Cathleen S. Colón-Emeric,et al.  Meta-analysis: Excess Mortality After Hip Fracture Among Older Women and Men , 2010, Annals of Internal Medicine.

[17]  I. Reid,et al.  Effect of osteoporosis treatment on mortality: a meta-analysis. , 2010, The Journal of clinical endocrinology and metabolism.

[18]  K. Michaëlsson,et al.  Cardiovascular diseases and risk of hip fracture. , 2009, JAMA.

[19]  Marcelo Coca-Perraillon,et al.  Incidence and mortality of hip fractures in the United States. , 2009, JAMA.

[20]  A. Wolk,et al.  Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort , 2009, BMJ : British Medical Journal.

[21]  C. Cooper,et al.  Excess mortality following hip fracture: a systematic epidemiological review , 2009, Osteoporosis International.

[22]  J. Eisman,et al.  Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. , 2009, JAMA.

[23]  K. Michaëlsson,et al.  Simply ask them about their balance--future fracture risk in a nationwide cohort study of twins. , 2008, American journal of epidemiology.

[24]  Ari Heinonen,et al.  Shifting the focus in fracture prevention from osteoporosis to falls , 2008, BMJ : British Medical Journal.

[25]  Martha Timmer,et al.  Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis , 2007, Annals of Internal Medicine.

[26]  G. Mcclearn,et al.  Telomere length predicts survival independent of genetic influences , 2007, Aging cell.

[27]  E. Fisher,et al.  Excess mortality following hip fracture: the role of underlying health status , 2007, Osteoporosis International.

[28]  R. May Gender, immunity and the regulation of longevity. , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  K. Michaëlsson,et al.  Leisure Physical Activity and the Risk of Fracture in Men , 2007, PLoS medicine.

[30]  Juni Palmgren,et al.  The Swedish Twin Registry in the Third Millennium: An Update , 2006, Twin Research and Human Genetics.

[31]  John Tower,et al.  Sex-specific regulation of aging and apoptosis , 2006, Mechanisms of Ageing and Development.

[32]  K. Michaëlsson,et al.  Genetic effects on physical activity: results from the Swedish Twin Registry. , 2006, Medicine and science in sports and exercise.

[33]  Claude Bouchard,et al.  Genetics of food intake and eating behavior phenotypes in humans. , 2006, Annual review of nutrition.

[34]  J. Sastre,et al.  Role of mitochondrial oxidative stress to explain the different longevity between genders. Protective effect of estrogens , 2006, Free radical research.

[35]  C. Moran,et al.  Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study , 2005, BMJ : British Medical Journal.

[36]  H. Quan,et al.  Coding Algorithms for Defining Comorbidities in ICD-9-CM and ICD-10 Administrative Data , 2005, Medical care.

[37]  K. Michaëlsson,et al.  Genetic liability to fractures in the elderly. , 2005, Archives of internal medicine.

[38]  A. Aviv,et al.  The longevity gender gap: are telomeres the explanation? , 2005, Science of aging knowledge environment : SAGE KE.

[39]  E. Glader,et al.  Cost of stroke in Sweden: An incidence estimate , 2004, International Journal of Technology Assessment in Health Care.

[40]  A. Case,et al.  Sex differences in morbidity and mortality , 2004, Demography.

[41]  N. Martin,et al.  The epidemiology and genetics of smoking initiation and persistence: crosscultural comparisons of twin study results. , 2004, Twin research : the official journal of the International Society for Twin Studies.

[42]  C. Cooper,et al.  Association of birth weight with osteoporosis and osteoarthritis in adult twins. , 2003, Rheumatology.

[43]  E. Glader,et al.  Cost of stroke in Sweden: an incidence estimate. , 2003, International journal of technology assessment in health care.

[44]  O. Johnell,et al.  The components of excess mortality after hip fracture. , 2003, Bone.

[45]  P. Lichtenstein,et al.  The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies , 2002, Journal of internal medicine.

[46]  P. Royston,et al.  Flexible parametric proportional‐hazards and proportional‐odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects , 2002, Statistics in medicine.

[47]  K. Michaëlsson,et al.  Association between oxidative stress and bone mineral density. , 2001, Biochemical and biophysical research communications.

[48]  C. Cooper,et al.  Epidemiology of osteoporosis. , 2001, Rheumatic diseases clinics of North America.

[49]  Olof Johnell,et al.  Hormone replacement therapy and risk of hip fracture: population based case-control study , 1998, BMJ.

[50]  O Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. , 1996, BMJ.

[51]  Johan Calltorp,et al.  Health care with equity and cost containment , 1996, The Lancet.

[52]  C. Cooper,et al.  Epidemiology of osteoporosis. , 2002, Best practice & research. Clinical rheumatology.

[53]  J. Wark,et al.  The prevention and treatment of osteoporosis. , 1993, The New England journal of medicine.

[54]  J. Woo,et al.  Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture , 1992, Calcified Tissue International.

[55]  C. Cooper,et al.  Hip fractures in the elderly: A world-wide projection , 1992, Osteoporosis International.

[56]  D. Rubin,et al.  The central role of the propensity score in observational studies for causal effects , 1983 .

[57]  Pär Stattin,et al.  Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. , 2013, European urology.

[58]  Sarah E Lamb,et al.  Interventions for preventing falls in older people living in the community. , 2009, The Cochrane database of systematic reviews.

[59]  J. Iwamoto,et al.  Efficacy of risedronate against hip fracture in patients with neurological diseases: a meta-analysis of randomized controlled trials. , 2008, Current Medical Research and Opinion.

[60]  Susan A. Murphy,et al.  Monographs on statistics and applied probability , 1990 .

[61]  Nancy L Pedersen,et al.  The Swedish Twin Registry in the Third Millennium , 2002, Twin Research.

[62]  O. Johnell,et al.  Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish Hip Fracture Study Group. , 1998, BMJ.

[63]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[64]  L. Verbrugge,et al.  Sex differentials in health and mortality. , 1987, Health matrix.

[65]  K. Park [[Sex differences in mortality]]. , 1987, In'gu pogon nonjip = Journal of population and health studies.

[66]  K. Choi [Hip fracture]. , 1963, [Chapchi] Journal. Taehan Oekwa Hakhoe.