Does a Fracture at One Site Predict Later Fractures at Other Sites? A British Cohort Study

The extent to which a fracture at one skeletal site predicts further fractures at other sites remains uncertain. We addressed this issue using information from the UK General Practice Research Database, which contains the medical records of general practitioners; our study population consisted of all patients aged 20 years or older with an incident fracture during 1988 to 1998. We identified 222 369 subjects (119 317 women, 103 052 men) who had sustained at least one fracture during follow-up. There was a 2- to 3-fold increase in the risk of subsequent fractures at different skeletal sites. A patient with a radius/ulna fracture had a standardized incidence ratio (SIR) of 3.0 (95% confidence interval 2.9–3.1) for fractures at a different skeletal site; for initial vertebral fracture, this ratio was 2.9 (2.8–3.1) and for initial femur/hip fracture it was 2.6 (2.5–2.7). The SIRs were generally higher among men than women. Men aged 65–74 years with a radius/ulna fracture or vertebral fracture had substantially higher rates of subsequent femur/hip fractures than expected; SIRs were 6.0 (3.4–9.9) and 13.4 (7.3–22.5). Corresponding SIRs among women of similar age were 3.3 (2.8–3.9) and 5.8 (4.1–8.1), respectively. Men and women aged 65 years or older with a vertebral fracture had a 5-year risk of femur/hip fracture of 6.7% and 13.3%, respectively. Our results indicate that fractures at any site are strong risk factors for subsequent fractures, among both elderly men and women. Received: 19 November 2001 / Accepted: 13 February 2002     

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     

Costs Induced by Hip Fractures: A Prospective Controlled Study in Belgium

The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown. We assessed the direct medical costs induced by hip fractures during and after hospitalization. Hospital costs of 170 consecutive Belgian women with hip fracture were gathered. During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay. A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture. The mean cost of the acute hospital stay was C8667, and the mean 1-year hip-fracture-related extra costs after hospitalization was C6636. During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p<0.001). Although health care costs increased with age, hip-fracture-related extra costs after hospitalization seemed similar in those below or above 81 years old. These extra costs amounted to C7710 in women not living in nursing homes at the time of fracture, and to C3479 in women who lived in nursing homes. Health or mental status before hip fracture seemed not to affect extra costs. Taking into account the higher mortality of women with hip fracture, the extra costs during the acute hospital stay and during the 1-year follow-up amounted to a mean C 15151. In conclusion, both acute hospital stays and subsequent medical care contribute significantly to medical costs induced by hip fractures. Received: 12 April 1999 / Accepted: 9 November 1999     

Age- and Gender-Specific Rate of Fractures in Australia: A Population-Based Study

There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35 – 55 years, the fracture rate (persons per 10 000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles’) (18 and 4) and humerus (11 and 3), and were 3–4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10 000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men. Received: 6 October 1998 / Accepted: 16 February 1999     

Vertebral Fractures Predict Subsequent Fractures

This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During 4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2–5.3) than women (SIR, 2.7; 95% CI, 2.4–3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11–14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8–2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01–2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip. Received: 2 September 1998 / Accepted: 9 February 1999     

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     

Forearm Fractures as Predictors of Subsequent Osteoporotic Fractures

To assess the ability of distal forearm fractures to predict future fractures, we conducted a population-based retrospective cohort study among the 1288 residents (243 men, 1045 women) of Rochester, Minnesota age 35 years or older who experienced their first distal forearm fracture in 1975–94. During 9664 person-years of follow-up, 548 patients experienced 1109 subsequent fractures, excluding 195 that occurred on the same day as the index forearm fracture. The cumulative incidence of any subsequent fracture was 55% by 10 years and 80% by 20 years following the initial distal forearm fracture. Compared to expected fracture rates in the community, the risk of a hip fracture following the index forearm fracture was increased 1.4-fold in women (95% CI, 1.1–1.8) and 2.7-fold in men (95% CI, 0.98–5.8). In women, the risk of hip fracture differed by age, as we had found in a previous study. Women over age 70 had a 1.6-fold increase (95% CI, 1.2–2.0) in subsequent hip fracture risk whereas women who sustained their first forearm fracture before age 70 years did not have significantly increased risk. By contrast, vertebral fractures were significantly increased at all ages, with a 5.2-fold increase (95% CI, 4.5–5.9) in risk among women and a 10.7-fold increase (95% CI, 6.7–16.3) among men following a first distal forearm fracture. The increased risk in men suggests that a sentinel forearm fracture should not be ignored. Among the women, we also found a missed opportunity for intervention as hormone replacement therapy was underutilized. Received: 8 May 1998 / Accepted: 16 October 1998     

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     

Prevalent Vertebral Deformity Predicts Incident Hip though not distal Forearm Fracture: Results from the European Prospective Osteoporosis Study

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40 348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1–9.4) and a weak predictor of ‘other’ limb fractures (RR = 1.6; 95% CI 1.1–2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6–1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0–17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and ‘other’ limb fractures; however, they do not predict distal forearm fractures. Received: 23 February 2000 / Accepted: 11 August 2000     

Recognition of Vertebral Fracture in a Clinical Setting

Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists’ readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist’s summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition. Received: 15 November 1999 / Accepted: 23 December 1999     

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     

Mortality Associated with Vertebral Deformity in Men and Women: Results from the European Prospective Osteoporosis Study (EPOS)

Clinically apparent vertebral deformities are associated with reduced survival. The majority of subjects with radiographic vertebral deformity do not, however, come to medical attention. The aim of this study was to determine the association between radiographic vertebral deformity and subsequent mortality. The subjects who took part in the analysis were recruited for participation in a multicentre population-based survey of vertebral osteoporosis in Europe. Men and women aged 50 years and over were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Radiographs were evaluated morphometrically and vertebral deformity defined according to established criteria. The participants have been followed by annual postal questionnaire – the European Prospective Osteoporosis Study (EPOS). Information concerning the vital status of participants was available from 6480 subjects, aged 50–79 years, from 14 of the participating centres. One hundred and eighty-nine deaths (56 women and 133 men) occurred during a total of 14 380 person-years of follow-up (median 2.3 years). In women, after age adjustment, there was a modest excess mortality in those with, compared with those without, vertebral deformity: rate ratio (RR) = 1.9 (95% confidence interval (CI) 1.0,3.4). In men, the excess risk was smaller and non-significant RR = 1.3 (95% CI 0.9,2.0). After further adjusting for smoking, alcohol consumption, previous hip fracture, general health, body mass index and steroid use, the excess risk was reduced and non-significant in both sexes: women, RR = 1.6 (95% CI 0.9,3.0); men RR = 1.2 (95% CI 0.7,1.8). Radiographic vertebral deformity is associated with a modest excess mortality, particularly in women. Part of this excess can be explained by an association with other adverse health and lifestyle factors linked to mortality. Received: 12 June 1997 / Accepted: 6 November 1997     

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     

Digital X-ray Radiogrammetry Predicts Hip,Wrist and Vertebral Fracture Risk in Elderly Women: A Prospective Analysis from the Study of Osteoporotic Fractures

Digital X-ray radiogrammetry (DXR) is a technique that uses automated image analysis of standard hand radiographs to estimate bone mineral density (DXR-BMD). Previous studies have shown that DXR-BMD measurements have high precision, are strongly correlated with forearm BMD and are lower in individuals with prevalent fractures. To determine whether DXR-BMD measurements predict wrist, hip and vertebral fracture risk we conducted a case–cohort study within a prospective study of 9704 community-dwelling elderly women (the Study of Osteoporotic Fractures). We compared DXR-BMD, and BMD of the radius (proximal and distal), calcaneus, femoral neck and posteroanterior lumbar spine in women who subsequently suffered a wrist (n= 192), hip (n= 195), or vertebral fracture (n= 193) with randomly selected controls from the same cohort (n= 392–398). DXR-BMD was estimated from hand radiographs acquired at the baseline visit. The radiographs were digitized and the Pronosco X-posure System was used to compute DXR-BMD from the second through fourth metacarpals. Wrist fractures were confirmed by radiographic reports and hip fractures were confirmed by radiographs. Vertebral fractures were defined using morphometric analysis of lateral spine radiographs acquired at baseline and an average of 3.7 years later. Age-adjusted odds ratio (OR, vertebral fracture) or relative hazard (RH, wrist and hip fracture) for a 1 SD decrease in BMD were computed. All BMD measurements were similar for prediction of wrist (RH = 1.5–2.1) and vertebral fracture (OR = 1.8–2.5). Femoral neck BMD best predicted hip fracture (RH = 3.0), while the relative hazards for all other BMD measurements were similar (RH = 1.5–1.9). These prospective data indicate that DXR-BMD performs as well as other peripheral BMD measurements for prediction of wrist, hip and vertebral fractures. Therefore, DXR-BMD may be useful for prediction of fracture risk in clinical settings where hip BMD is not available. Received: 27 April 2001 / Accepted: 10 October 2001     

Bone Mineral Density and Vertebral Fractures in Men

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia. Received: 27 October 1998 / Accepted: 22 February 1999     

Can Historical and Functional Risk Factors be Used to Predict Fractures in Community-Dwelling Older Adults? Development and Validation of a Clinical Tool

The objectives of the study were: (1) to evaluate the contribution of impaired functional status, cognition and medication to fracture risk; (2) to determine whether risk factor profiles differ between regionally and socially diverse populations; and (3) to develop and validate a simple fracture prediction instrument for use in older adults using easily obtainable clinical information. A prospective population-based cohort study with 6–10 years of follow-up was carried out: the Duke and Iowa Established Populations for the Epidemiologic Study of the Elderly (EPESE), with in-person interviews in North Carolina and Iowa. The participants were community-dwelling men and women aged 65 years or over without a history of previous fracture at the baseline interview (n = 7654). The measurements were potential risk factors for osteoporosis and falls including: demographic factors, co-morbidities, medications, functional status measures, and physical measures. These were examined for association with self-reported subsequent hip fractures and fractures at any site using survival analysis. The resulting multivariable model was simplified and validated in a separate cohort. Test operating characteristics at 3 years were estimated using logistic regression. There were a total of 842 fractures in both cohorts including 382 hip fractures. Significant risk factors for all subsequent fractures and/or hip fracture in the developmental cohort included female sex (relative hazard 1.9–2.3), lowest quartile of body mass index (1.3), Caucasian race (2.1–2.8), one or more Rosow–Breslau physical function impairments (1.8–2.1), age over 75 years (2.1), history of stroke (1.9), cognitive impairment (2.2), one or more impairments in the activities of daily living (1.5) and anti-seizure medication use (2.0). Three predicitive models were highly significantly correlated with subsequent fractures with c-statistics in the developmental cohort at 3 and 6 years of 0.640–0.789. A simple count of risk factors had similar discriminative ability to the full model with a linear 35–65% increase in hazard of all fractures and hip fracture for each additional risk factor. In the validation cohort, the above variables were less potent predictors of fracture with only sex, body mass index and Rosow–Breslau impairment achieving significance. The predictive models including risk factor count remained significant in the validation set although the discriminative ability of the model was poor, with c-statistics of 0.574–0.749. Although there is no cut-point where fracture risk dramatically increases, patients can be counselled that there is a linear 77% increase in risk of hip fracture, and 29% increase in any fracture risk, with each additional risk factor they possess. Functional status impairment is an important predictor of fracture in older community-dwelling adults. The contribution of risk factors to fracture risk may differ between distinct populations. Received: 28 January 2002 / Accepted: 8 July 2002     

Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n= 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p= 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p= 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease. Received: 29 September 1999 / Accepted: 10 November 1999     

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     

Femoral Neck and Intertrochanteric Fractures Have Different Risk Factors: A Prospective Study

The aim of this study was to determine whether both types of hip fracture, femoral neck and intertrochanteric, have similar risk factors. A prospective cohort study was carried out on community-dwelling elderly women in four areas of the United States: Baltimore, MD; Pittsburgh, PA; Minneapolis, MN and Portland, OR. The participants were 9704 Caucasian women, 65 years and older, of whom 279 had fractured their femoral neck and 222 had fractured their trochanteric region of the proximal femur. The predictors used were the bone mass of the calcaneus and proximal femur, anthropometry, history of fracture (family and personal), medication use, functional status, physical activity and visual function. The main outcome measures were femoral neck and intertrochanteric fractures occurring during an average of 8 years of follow-up. In multivariate proportional hazards models, several risk factors increased the risk of both types of hip fracture; including femoral neck bone density and increased functional difficulty. In hazard regression models that directly compared risk factors for the two types of hip fracture, calcaneal bone mineral density (BMD) predicted femoral neck fractures more strongly than intertrochanteric fractures (OR = 1.16; 95% CI = 1.02–1.31). Steroid use and impaired functional status also predicted femoral neck fractures instead of intertrochanteric fractures. Poor health status (OR = 0.74; 95% CI = 0.55–1.00) predicted intertrochanteric fractures more strongly than femoral neck fractures. We conclude that femoral neck fractures are largely predicted by BMD and poor functional ability while aging and poor health status predispose to intertrochanteric fractures. Received: 8 February 2000 / Accepted: 10 June 2000     

Survival after Hip Fracture: Short- and Long-Term Excess Mortality According to Age and Gender

The purpose of this study was to analyze the excess mortality after hip fracture and to reveal whether, and eventually when, the excess mortality vanished in different groups of age and gender. A population-based, prospective, matched-pair, cohort study among persons 50 years of age and older was conducted involving 1338 female and 487 male hip fracture patients with 11 086 and 8141 controls respectively. Occurrence of hip fracture and mortality were recorded from 1986 until 1995. We studied the excess mortality of the hip fracture patients versus controls by using Kaplan–Meier curves and extended Cox regression with hip fracture (yes/no) as time-dependent covariate. The male hip fracture patients had higher mortality than the women the first year after the injury, irrespective of age, both in absolute terms (31% and 17% respectively) and relative to their age-matched controls. The relative risk (RR) of dying within 1 year for hip fracture patients versus controls was 3.3 (95% confidence interval (CI) 2.1–5.2) for women and 4.2 (95% CI 2.8–6.4) for men below 75 years of age. The corresponding figures for persons 85 years and older were 1.6 (95% CI 1.2–2.0) for women and 3.1 (95% CI 2.2–4.2) for men. All groups of age and gender, except women 85 years and older, had a large and significant excess mortality lasting for many years after the hip fracture – at least 5–6 years for women below 75 years of age (RR = 3.2, 95% CI 1.9–5.6). The excess mortality after hip fracture for women 85 years and older had vanished after 3 months (RR = 1.0, 95% CI 0.8–1.1). When referring to the excess mortality after hip fracture it is therefore necessary to specify sex, age and time since injury. Received: 15 September 1998 / Accepted: 23 December 1998