Long-Term Risk of Osteoporotic Fracture in Malmö

The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in Malmo¨, Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20–30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated. Received: 9 November 1999 / Accepted: 2 February 2000     

An Assessment Tool for Predicting Fracture Risk in Postmenopausal Women

Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women. Received: 7 November 2000 / Accepted: 23 May 2001     

Family History of Appendicular Fracture and Risk of Osteoporosis: A Population-Based Study

Family and twin studies demonstrate a strong genetic component to osteoporosis, suggesting that a positive family history for this disease may be an important clinical risk factor. We have therefore explored the extent to which a history of wrist fracture in a female first-degree relative was associated with an increased risk of prevalent fracture at both appendicular and vertebral sites in a cross-sectional study design. One thousand and three Caucasian women (age range 45–64 years) were studied from a UK population cohort. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Appendicular fractures (wrist and hip) were recorded by questionnaire and validated from radiographs and hospital records. Vertebral fractures were assessed using radiologic survey of the thoracolumbar spine and semi-automated morphometric analysis. A positive family history of osteoporotic fracture (hip and/or wrist) in either a mother and/or sister was reported in 138 of the 1003 women. When compared with those with a negative family history of fracture, BMD was significantly reduced in those with a positive history at both the spine (p = 0.02) and the hip (p = 0.02). In total, there were 63 validated fragility fractures found in the 1003 women (16 wrist, 6 hip and 41 vertebral). Family history of osteoporotic fracture was associated with an increased total risk for osteoporotic fracture, with an odds ratio (95% confidence interval) of 2.02 (1.02, 3.78). Site-specific analysis showed that a positive family history of wrist fracture was associated with a considerably elevated risk of wrist fracture, with an odds ratio of 4.24 (1.44, 12.67). These increases in risk remained after adjustment for BMD, suggesting that other genetic factors account for the familial risk of osteoporosis and fracture. Received: 20 August 1998 / Accepted: 25 January 1999     

Lifetime and Five-Year Age-Specific Risks of First and Subsequent Osteoporotic Fractures in Postmenopausal Women

We examined the incidence of fragility fractures in Australian women 50 years of age and over using a Markov process with Monte Carlo simulations. The lifetime risks and the risks of sustaining first and subsequent clinically diagnosed fractures at osteoporotic sites were estimated according to age, nursing home entry and mortality rates. Hip and spine fractures were evaluated individually and fractures of humerus, forearm, wrist, ribs, pelvis, upper leg (excluding proximal femur) and tibia/fibula were considered in combination. The model predicted that 42.1% of women aged 50 years will sustain at least one fracture in their remaining lifetime, of whom half are expected to sustain multiple fractures. The lifetime risks of sustaining hip, clinical spine and other fractures were 17.0%, 9.6% and 30.4%, with the risks of multiple fractures at these sites estimated at 19.5%, 39.7% and 35.7% respectively. The proportion of women expected to sustain their first fracture increased from 1.9% of the population under 55 years of age up to 49.1% of women over 89 years of age. The 5-year age-specific risks of sustaining any subsequent fractures increased from 2.8% of women under the age of 55 years to 61.6% for women age 89 years and over. The increased risks of new fractures following a first fracture lead to a considerable burden of multiple fractures. Received: 2 February 2000 / Accepted: 5 June 2000     

Ten Year Probabilities of Osteoporotic Fractures According to BMD and Diagnostic Thresholds

The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in Malmo¨, Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes. Received: 14 December 2000 / Accepted: 2 July 2001     

Fractures Before Menopause: A Red Flag for Physicians

There is substantial interest in the early identification of women at risk for osteoporotic fractures, so that preventive measures may be instituted early. We examined whether women with a history of fractures before menopause were at an increased risk of fractures after menopause. We obtained information about any lifetime fractures of the hip, arm, spine, wrist, leg, ankle, foot and finger from 9086 ambulatory white women ages 65 years and older participating in the Study of Osteoporotic Fractures. We also measured bone mineral density and recorded history of falls, maternal fracture history, drug use, diet, functional status, and other characteristics commonly associated with osteoporotic fractures. We used proportional hazards models to estimate the effects of fractures that occurred before menopause on the risk of fractures after menopause, in particular those that occurred during the 12 years of study follow-up. The risk of fractures of all types during the study period was greater among women with a premenopausal fracture of any type compared with women without a premenopausal fracture (hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.14–1.56; p<0.001). Adjustment for possible confounders, including bone mineral density, had only a modest effect (HR, 1.25; 95% CI, 1.03–1.50; p<0.02). An increased risk of fracture among women with a premenopausal fracture was also seen after stratification by estrogen use, propensity to fall and maternal fracture history. Premenopausal fractures are therefore a risk factor for subsequent fractures independent of other risk factors for osteoporotic fractures, such as bone mineral density. A fracture history, including fractures before menopause, should be obtained when making decisions about preventive treatments. Received: 17 April 2000 / Accepted: 14 June 2000     

A Population-Based Study of Fracture Incidence in Southern Tasmania: Lifetime Fracture Risk and Evidence for Geographic Variations within the Same Country

Symptomatic fractures are a significant problem in terms of both morbidity and financial cost. Marked variation in both total and site-specific fracture incidence has been documented internationally but there is limited within-country data. This prospective population-based study documented the incidence of all symptomatic fractures occurring from July 1, 1997 to June 30, 1999 in adults ≥50 years of age resident in Southern Tasmania (total population ≥50 years: 64 688). Fractures were ascertained by reviewing reports from all the radiology providers within the area. There were 701 fractures in men and 1309 fractures in women. The corresponding fracture incidence in men and women was 1248 and 1916 per 100 000 person-years, respectively. Residual lifetime fracture risk in a person aged 50 years was 27% for men and 44% for women with fractures other than hip fractures constituting the majority of symptomatic fracture events. These fracture risk estimates remained remarkably constant with increasing age. In comparison to Geelong, there were significantly lower hip fracture rates (males: RR 0.59, 95% CI 0.45–0.76; females: RR 0.61, 95% CI 0.53–0.71) but significantly higher distal forearm fractures (males: RR 1.87, 95% CI 1.10–3.78; females: RR 1.31, 95% CI 1.11–1.55) and total fractures in men (RR 1.31, 95% CI 1.17–1.46) but not women (RR 1.05, 95% CI 0.98–1.13). In contrast, Southern Tasmania had lower age-standardized rates of all fractures compared with Dubbo (RR 0.28–0.79). In conclusion, this study provides compelling evidence that fracture incidence varies between different geographic sites within the same country, which has important implications for health planning. In addition, the combination of high residual fracture risk and short life expectancy in elderly subjects suggests fracture prevention will be most cost-effective in later life. Received: 27 April 2000 / Accepted: 16 August 2000     

Differences in Risk Factor Patterns Between Cervical and Trochanteric Hip Fractures

The two types of hip fracture – cervical and trochanteric femoral fractures – are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case–control study in Swedish women, 50–81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15–1.32) compared with an OR of 1.06 (95% CI 0.97–1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0.91–0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12–1.95) for trochanteric fractures and 1.22 (95% CI 0.98–1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0.55 (95% CI 0.33–0.92) compared with 1.00 (95% CI 0.71–1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions. Received: 22 March 1999 / Accepted: 28 May 1999     

DXA of the Hip and Heel Ultrasound but not Densitometry of the Fingers Can Discriminate Female Hip Fracture Patients from Controls: A Comparison Between Four Different Methods

Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent years quantitative ultrasound (QUS) of the heel are the most established methods for assessing hip fracture risk. Measurement of the fingers offers a new approach. We performed DXA of the proximal femur, QUS of the heel and fingers, and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized women, 65–85 years of age, with a first hip fracture and compared them with 195 randomly selected age-matched controls. Bone mineral density (BMD) of the femoral neck and heel Stiffness Index were significantly lower among cases than among controls (by 15% and 17%, respectively; p<0.0001), whereas no significant differences were found for finger measurements. When applying the WHO criterion of osteoporosis, 62–98% of the patients were classified as osteoporotic, compared with 19–85% of the controls, depending on method and site. The risks of hip fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD, heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4–5.5), 3.4 (95% CI 2.2–5.0), 1.0 (95% CI 0.7–1.3) and 1.2 (95% CI 0.8–1.6), respectively. Compared with women with normal BMD of the femoral neck, those classified as osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those classified as osteoporotic had an odds ratio of 63 (95% CI 8–501). We conclude that hip DXA and heel QUS have similar capacities to discriminate the risk of a first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques for differentiating female hip fracture patients from controls. Received: 10 March 2000 / Accepted: 21 September 2000     

Impact of Hip and Vertebral Fractures on Quality-Adjusted Life Years

The objective of the study was to estimate the impact of hip and vertebral fractures on quality of life in postmenopausal women using a preference-based health measure that is appropriate for economic evaluations and to investigate correlates of health outcome. Interviews to assess health-related quality of life, which also documented other health conditions and characteristics, were undertaken in women age 50 years and older without osteoporotic fractures compared with women with hip and/or vertebral fracture(s). Health status was characterized by self-reported physical limitations and the mental and physical component summary scores of the SF-36. Quality-adjusted life years (QALYs), which reflect each individual’s assessment of her overall health utility, were estimated with time tradeoff values. Regression methods were used to examine QALY correlates (e.g. time since fracture) for each fracture group and to estimate differences in QALYs between fracture and non-fracture subjects after accounting for other patient characteristics. Among 382 women ages 50–96 years, fracture subjects were significantly older, less likely to use hormone replacement therapy and more likely to report physical limitations than non-fracture subjects. On the QALY scale, where 1 represents perfect health and 0 represents death, mean QALY values were 0.82 (95% CI: 0.76, 0.87) among 114 women with one or more vertebral fractures and 0.63 (95% CI: 0.52, 0.74) among 67 with hip fracture compared with 0.91 (95% CI: 0.88, 0.94) among 201 women without fracture. No significant correlates of QALYs were identified among women with vertebral fracture alone. Among hip fracture subjects, time since hip fracture and presence of a vertebral fracture were significant correlates of QALYs. In multiple regression analyses, estimated QALY differences (fracture minus non-fracture subjects) ranged from –0.05 to –0.55 and were equivalent to losses of 20–58 days, 23–65 days and 115–202 days per year for vertebral fracture (p= 0.001), hip fracture (p= 0.009) and hip plus vertebral fracture (p<0.001) subjects, respectively, depending on age. Thus to adequately assess the cost-effectiveness of osteoporosis treatment, the negative impact of vertebral fractures on QALYs, even among women who have survived a hip fracture, must be considered. Received: 2 February 2001 / Accepted: 23 July 2001