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Boning Up: Mortality Risk Associated with Fractures
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant to Cephalon and Ventus and serves on the speaker's bureau of Cephalon and Boehringer Ingelheim.
Synopsis: In older women and men, all low-trauma fractures were associated with increased mortality risk for at least 5 years. Subsequent fracture increased that risk.
Source: Bliuc D, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009;301:513-521.
This report comes from the Dubbo Osteoporosis Epidemiology Study, which is a longitudinal population-based study of women and men aged 60 years and older living in Dubbo, Australia.1 The study entire group was 2245 women and 1760 men who were mostly (98.6%) white. Over an 18-year period of follow-up, 952 of the women and 343 of the men had at least one low-trauma bone fracture. Of this group of individuals who had bone fractures, 452 of the women and 162 of the men agreed to participate in detailed, ongoing follow-up. From the time of recruitment, these individuals were studied every other year for an average of about 18 years. Data collected included physical activity, dietary calcium intake, cigarette smoking, alcohol consumption, number of falls in the last year, comorbid illnesses, medications, anthropometric measurements, bone mineral density (BMD), quadriceps strength, and sway.
Fractures were identified from X-ray reports obtained from the radiological services for the entire Dubbo area. Circumstances surrounding the fracture were obtained by personal interviews. The authors excluded from analysis high-trauma fractures, pathological fractures, and fractures of the head, fingers, or toes. Fractures were analyzed in 4 separate groups: hip, vertebral, major, and minor fractures. Major fractures included pelvis, distal femur, proximal tibia, 3 or more simultaneous ribs, and proximal humerus. Minor fractures included all remaining osteoporotic fractures.
Mortality status of all fracture participants was identified from systematic searches, including the Australian Bureau of Statistics for each year of the study.
Fracture and Mortality Rates for the Entire Population. There were 952 fractures in women and 343 in men for the Dubbo population aged 60 years and older during the period of observation. These equated to an average fracture incidence of 32 per 1000 person-years in women and 17 per 1000 person-years in men. During this same period of time, mortality rates were 4.3 per 100 person-years and 5.5 per 100 person-years for women and men, respectively. Among the study participants, 461 deaths were observed in women and 197 in men, yielding substantially higher mortality rates of 7.8 per 100 person-years and 11.3 per 100 person-years in women and men, respectively. Standardized mortality ratios for fracture type for the first 5 years after fracture are shown in the Table (see right).
For each age group, mortality in the fracture participants was consistently higher than that in the general population. Mortality rates were higher for those sustaining hip, vertebral, major, and minor fractures, in that order. Mortality was higher for men than for women at all age groups, most markedly in the older age groups.
Absolute and standardized mortality rates were highest in the first 5 years following fracture, for all fracture types. Of the excess mortality in the first 5 years after a fracture, hip, vertebral, and nonhip, nonvertebral fractures were each associated with approximately one-third of deaths (37%, 35%, and 29%, respectively). For the 5- to 10-year postfracture interval, mortality rates remained elevated only after hip fractures. After 10 years, mortality rates were not different from that of an appropriately age-matched population, even for those who had experienced hip fractures.
Approximately 30% of women and 22% of men experienced another fracture during the study period over a median of 5.1 years. Of these, 49% of the women and 74% of the men died. Subsequent fracture was associated with an increased mortality hazard ratio (HR) of 1.91 in women and 2.99 in men. The 5-year mortality for those with a subsequent fracture was greater than for those who only had one fracture. Mortality risk following a subsequent fracture declined over time, but still remained higher than the general population, even after 5 years.
Overall, the major causes of death were cardiac (27%), respiratory (26%), cerebrovascular (15%), and malignancy (13%). Fracture was mentioned in only 10.5% of death certificates, primarily hip and vertebral fracture. Osteoporosis without a fracture was mentioned in an additional 2.5% of death certificates.
Fracture and Mortality Rates for the Detailed Follow-up Group. For the subset of participants who agreed to detailed follow-up, those who died were older, weighed less, had lower bone mineral density (BMD), and had weaker quadriceps. Women who died also had higher sway. Among those who died, there was more cardiovascular illness in women and more neurological and respiratory illness in men.
After controlling for multiple confounders, age, subsequent fracture, and weaker quadriceps were associated with increased mortality for all participants. In women, lower bone mineral density, smoking, and sway predicted increased risk of death, while in men, decreased physical activity was an independent predictor of mortality.
A subanalysis to assess the relationship between fracture and mortality independent of low bone mineral density was performed for 347 female fracture and 129 male fracture participants with the same numbers of age- and BMD-matched controls. Over about a 5-year period, the mortality rates for women matched by BMD groups were higher than that of the general population, but were similar between those with and without fractures. In men, fracture participants had higher associated mortality rates than their BMD-matched, nonfractured counterparts.
The association between fracture and mortality is not new.2-4 What IS new in this study is the demonstration of increased mortality associated with all major fractures at all ages (older than age 60) and both sexes, and even with minor fractures in older age groups. Mortality was increased for the first 5 years following fractures for all fracture groups except for hip fractures, where mortality rates remained elevated for up to 10 years. In this current study, 30% of all post-hip fracture deaths occurred in the first 6 months and 21% in the next 18 months.
Of the outcomes of fractures, least is known about the relationship between nonhip fractures. This paper is the first report of an increased mortality associated with minor fractures in older people. These findings suggest that we should take nonhip, nonvertebral fractures more seriously. In this study, such fractures accounted for about half of all low-trauma fractures and were associated with more than 40% of all deaths. They are also associated with increased subsequent fracture risk.
Osteoporotic fractures in older people are a huge and growing public health problem, associated with significant cost in dollars, health, and lives.5,6 The current report indicates that the cost of bone fractures is not limited to those of the spine and hip.
So, what to do for our patients, beyond the usual caveats about diet, sleep, exercise, alcohol, and tobacco? A recent randomized study of bisphosphonate treatment of men and women soon after a hip fracture reported significantly decreased mortality,7 and might be worth considering. And we need to recognize that broken bones help identify patients that are at risk.
1. Simons LA, et al. The Dubbo study: An Australian prospective community study of the health of elderly. Aust N Z J Med 1990;20:783-789.
2. Center JR, et al. Mortality after all major types of osteoporotic fracture in men and women: An observational study. Lancet 1999;353:878-882.
3. Cauley JA, et al. Risk of mortality following clinical fractures. Osteoporos Int 2000;11:556-561.
4. Haentjens P, et al; Network on Male Osteoporosis in Europe (NEMO). Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men. J Bone Miner Res 2004;19:1933-1944.
5. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359: 1761-1767.
6. Cooper C. The crippling consequences of fractures and their impact on quality of life. Am J Med 1997;103: 12S-17S.
7. Lyles KW, et al; HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007;357: 1799-1809.