Effect and Offset of Effect of Treatments for Hip Fracture on Health Outcomes

We investigated the cost-effectiveness of treatments that reduce the risk of hip fracture using a computer simulation model. Cost-effectiveness was measured as cost per quality-adjusted life-year (QALY) gained using a threshold value for cost-effectiveness of $30.000/QALY gained. The baseline simulations assumed a 5-year intervention that reduced the risk of hip fracture by 50% during the intervention period, and an effect which reversed to the pretreatment risk during the next 5 years. Sensitivity analyses inlcuded the effects of age, different fracture risks, and different treatment costs and duration of therapeutic effect once treatment was stopped. Cost-effectiveness was critically dependent upon absolute risk determined by the age and the relative risk of hip fracture at any given age. Reasonable cost-effectiveness was shown even with relatively high intervention costs for women with a risk about twice the average at the age of 70 or more years. Cost-effectiveness was critically dependent upon the assumptions made concerning offset of effect of intervention after the end of treatment. Where no residual effect was assumed, it was difficult to show cost-effectiveness from any intervention except for the most effective and least expensive. Conversely, cost-effectiveness improved considerably where effectiveness persisted for a longer time. These studies support the view that intervention in the elderly with agents affecting skeletal metabolism alone may be preferred to such interventions at the time of the menopause, and that offset time, hitherto poorly characterized, is a critical component of cost-effectiveness, particularly in younger women. Received: 26 May 1998 / Accepted: 8 February 1999     

Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden

The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in men and women, based on data from Sweden. We modeled the effects of a treatment costing $500 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect for a further 5 years. Sensitivity analyses included a range of effectiveness (10-50%) and a range of intervention costs ($200–500/year). Data on costs and risks were from Sweden. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of approximately $45,000/QALY gained was used. Cost of added years was included in a sensitivity analysis. With the base case ($500 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.2% at the age of 50 years to 7.4% at the age of 80 years. Similar results were observed in men except that the threshold for cost-effectiveness was higher at younger ages than in women (2.0 vs 1.2%, respectively, at the age of 50 years). Intervention thresholds were sensitive to the assumed effectiveness and intervention cost. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age, and that available treatments can be targeted cost-effectively to individuals at moderately increased fracture risk.     

Cost-effective osteoporosis treatment thresholds: the United States perspective

Summary A United States-specific cost-effectiveness analysis, which incorporated the cost and health consequences of clinical fractures of the hip, spine, forearm, shoulder, rib, pelvis and lower leg, was undertaken to identify the 10-year hip fracture probability required for osteoporosis treatment to be cost-effective for cohorts defined by age, sex, and race/ethnicity. A 3% 10-year risk of hip fracture was generally required for osteoporosis treatment to cost less than $60,000 per QALY gained. Introduction Rapid growth of the elderly United States population will result in so many at risk of osteoporosis that economically efficient approaches to osteoporosis care warrant consideration. Methods A Markov-cohort model of annual United States age-specific incidence of clinical hip, spine, forearm, shoulder, rib, pelvis and lower leg fractures, costs (2005 US dollars), and quality-adjusted life years (QALYs) was used to assess the cost-effectiveness of osteoporosis treatment ($600/yr drug cost for 5 years with 35% fracture reduction) by gender and race/ethnicity groups. To determine the 10-year hip fracture probability at which treatment became cost-effective, average annual age-specific probabilities for all fractures were multiplied by a relative risk (RR) that was systematically varied from 0 to 10 until a cost of $60,000 per QALY gained was observed for treatment relative to no intervention. Results Osteoporosis treatment was cost-effective when the 10-year hip fracture probability reached approximately 3%. Although the RR at which treatment became cost-effective varied markedly between genders and by race/ethnicity, the absolute 10-year hip fracture probability at which intervention became cost-effective was similar across race/ethnicity groups, but tended to be slightly higher for men than for women. Conclusions Application of the WHO risk prediction algorithm to identify individuals with a 3% 10-year hip fracture probability may facilitate efficient osteoporosis treatment. The authors comprise the National Osteoporosis Foundation Guide Committee.     

Direct Medical Costs Attributable to Osteoporotic Fractures

Osteoporotic fractures are a major cause of morbidity in the elderly, the most rapidly growing segment of our population. We characterized the incremental direct medical costs following such fractures in a population-based cohort of men and women in Olmsted County, Minnesota. Cases included all County residents 50 years of age and older with an incident fracture due to minimal or moderate trauma between January 1, 1989 and January 1, 1992. For each case, a control of the same age (± 1 year) and sex who was attended in the local medical system in the same year was identified. Total incremental costs (cases – controls) in the year after fracture were estimated. Unit costs for each health service/procedure were obtained through the Mayo Cost Data Warehouse, which provides a standardized, inflation-adjusted estimate reflecting the national average cost of providing the service. Regression analysis was used to identify factors associated with incremental costs. There were 1263 case/control pairs; their average age was 73.8 years and 78% were female. Median total direct medical costs were $761 and $625, respectively, for cases and nonfracture controls in the year prior to fracture, and $3884 and $712, respectively, in the year following fracture. The highest median incremental costs were for distal femur ($11 756) and hip fractures ($11 241), whereas the lowest were for rib fractures ($213). Although hip fractures resulted in more incremental cost than any other fracture type, this amounted to only 37% of the total incremental cost of all moderate-trauma fractures combined. Regression analyses revealed that age, prior year costs and type of fracture were significant predictors of incremental costs (p<0.03 for all comparisons). The incremental costs of osteoporotic fractures are therefore substantial. Whereas hip fractures contributed disproportionately, they accounted for only one-third of the total incremental cost of fractures in our cohort. The use of incremental costs in economic analyses will provide a more accurate reflection of the true cost-effectiveness of osteoporosis prevention. Received: 13 November 2001 / Accepted: 6 March 2001     

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     

Intervention thresholds for osteoporosis in the UK

The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in women based on data from the UK. We modelled the effects of an intervention costing pound 350 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect (offset time) for a further 5 years. Sensitivity analyses included a range of treatment duration (3-10 years), intervention costs (pound 300-400/year) and offset times (0-15 years). Data on costs and risks were from the UK. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of pound 30,000/QALY gained was used. With the base case ( pound 350 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.1% at the age of 50 years to 9.0% at the age of 85 years. Intervention thresholds were sensitive to the assumed costs and offset time. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. Cost-effective scenarios were found for women at the threshold for osteoporosis from the age of 60 years. Treatment of established osteoporosis was cost-effective irrespective of age. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age and that available treatments can be targeted cost-effectively to individuals from the UK at moderately increased fracture risk.     

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     

The Burden of Osteoporotic Fractures: A Method for Setting Intervention Thresholds

The aim of this study was to assess the relationship between morbidity from hip fracture and that from other osteoporotic fractures by age and sex based on the population of Sweden. Osteoporotic fractures were designated as those associated with low bone mineral density (BMD) and those that increased in incidence with age after the age of 50 years. Severity of fractures was weighted according to their morbidity using utility values based on those derived by the National Osteoporosis Foundation. Morbidity from fractures other than hip fracture was converted to hip fracture equivalents according to their disutility weights. Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e. the morbidity associated with osteoporotic fractures was 3–5 times that accounted for by hip fracture. Excess moribidity decreased with age to approximately 1.25 between the ages of 85 and 89 years. On the assumption that the age- and sex-specific pattern of fractures due to osteoporosis is similar in different communities, the computation of excess morbidity can be utilized to determine the total morbidity from osteoporotic fractures from knowledge of hip fracture rates alone. Such data can be used to weight probabilities of hip fracture in different countries in order to take into account the morbidity from fractures other than hip fracture, and to modify intervention thresholds based on hip fracture risk alone. If, for example, a 10-year probability of hip fracture of 10% was considered an intervention threshold, this would be exceeded in women with osteoporosis aged 65 years and more, but when weighted for other osteoporotic fractures would be exceeded in all women (and men) with osteoporosis. Received: 1 May 2000 / Accepted: 1 December 2000     

Cost-effectiveness of fracture prevention in established osteoporosis

This study presents the results of a computer simulation model for calculating the cost-effectiveness and cost-utility of treating patients with established osteoporosis in order to reduce the risk of fractures. The results are based on Swedish data for risk of fracture and costs. The treatment intervention modelled is based on treatment of a 62-year-old woman with established osteoporosis. The cost per hip fracture avoided is 350000 SEK, assuming a 50% reduction in the risk of fracture due to 5 years of treatment. A sensitivity analysis for changes in the cost and effectiveness of treatment, the risk of fracture and the discount rate is performed. The cost per life-year gained and the cost per quality-adjusted life-year (QALY) gained is presented to enable comparison of the cost-effectiveness of treating osteoporosis with that of other health care interventions. A comparison between treating the same woman for osteoporosis and mild hypertension shows a cost per life-year gained of 220000 SEK and 128000 SEK respectively. Cost per QALY gained is very similar for the two interventions: 105 000 SEK and 103 000 SEK respectively. This model provides a tool to enable clinicians, administrators and health policy makers to analyze and understand the economic aspects of a major health policy issue.     

Economic Implications of Hip Fracture: Health Service Use, Institutional Care and Cost in Canada

As the burden of illness associated with hip fracture extends beyond the initial hospitalization, a longitudinal 1 year cohort study was used to analyze levels of health service use, institutional care and their associated costs, and to examine patient and residency factors contributing to overall 1 year cost. Patients in the study were aged 50 year and over, and had been admitted to an acute care facility for hip fracture in the Hamilton–Wentworth region of Canada from 1 April 1995 to 31 March 1996. Health care resources assessed included initial hospitalization, rehospitalization, rehabilitation, chronic care, home care, long-term care (LTC) and informal care. Regression analysis was used to determine the effects of age, gender, residence, survival and days of follow-up on 1 year cost. The mean 1 year cost of hip fracture for the 504 study patients was 26.527 Canadian dollars (95% Cl: $24.564–$28.490). One year costs were significantly different for patients who returned to the community ($21.385), versus those who were transferred to ($44.156), or readmitted to LTC facilities ($33.729) (p<0.001). Initial hospitalization represented 58% of 1 year cost for community-dwelling patients, compared with 27% for LTC residents. Only 59.4% of community-dwelling patients resided in the community 1 year following hip fracture, and 5.6% of patients who survived their first fracture experienced a subsequent hip fracture. Linear regression indicated place of residence, age and survival were all important contributors to 1 year cost (p<0.001). While the average 1 year cost of care was $26.527, the overall cost varied depending on a patient”s place of residence, age, and survival to 1 year. Annual economic implications of hip fracture in Canada are $650 million and are expected to rise to $2.4 billion by 2041. Received: 4 May 2000 / Accepted: 27 October 2000     

The Decision to Accept Treatment for Osteoporosis Following Hip Fracture: Exploring the Woman’s Perspective Using a Stage-of-Change Model

Despite the availability of medications that reduce fracture risk, most women who sustain a hip fracture are not evaluated or treated for osteoporosis. While a number of studies have attributed this to a lack of physician awareness, no studies have evaluated this problem from the patient’s perspective. To explore the process a woman negotiates when deciding to accept pharmacologic treatment for osteoporosis after hip fracture, we used a stage-of-change model to characterize a consecutive series of 70 postmenopausal women (mean age 85 years) admitted to a tertiary care hospital with an acute low-impact hip fracture between May 2000 and August 2000. We measured stage-of-change using a modified form of the Weinstein Precaution Adoption Process Model (PAPM). The majority of patients (65%) were ineligible because of dementia or delirium; only 29 were eligible and 21 were enrolled. Most women (62%) were in stages 1 or 2 of the PAPM, indicating that they were unaware of osteoporosis or had never considered pharmacologic treatment for it. The only factors associated with a more advanced PAPM stage (indicating active consideration or currently taking treatment) were a previous bone mineral density (BMD) evaluation (p= 0.007) and a diagnosis of osteoporosis (p= 0.001). Although 48% of women had a previous fragility fracture and osteoporosis knowledge was poor overall (mean score 52% correct), neither was associated with a more advanced PAPM stage in this sample. In conclusion, women evaluated after hip fracture were not ready to accept pharmacologic treatment for osteoporosis; they were unaware that they had osteoporosis or had never considered treatment for it. For a woman to advance through the behavior change process, she must first be made aware of the problem that requires a change in behavior. Physicians play a crucial role in promoting awareness of the diagnosis of osteoporosis after fracture, which in turn is associated with patient advancement through the behavior change process and the decision to accept pharmacologic intervention. The large number of cognitively impaired patients in this population, however, will certainly make efforts to improve osteoporosis awareness, diagnosis and intervention more challenging. Received: 20 August 2001 / Accepted: 12 December 2001     

Incremental Cost of Medical Care after Hip Fracture and First Vertebral Fracture: The Rotterdam Study

The aim of this study was to estimate the additional cost of medical care (the incremental cost) caused by incident hip and vertebral fractures, using a matched case cohort design within a longitudinal follow-up study. Incident hip fractures were recorded using the regular follow-up system of the Rotterdam Study. Incident vertebral fractures were recorded by morphometric comparison of spinal radiographs taken at intervals of 2.2 years on average. The matched control group was randomly selected from other participants of the Rotterdam Study in whom no fracture occurred during follow-up, but who were otherwise comparable at baseline. Cases were matched for age, gender, self-perceived health, ability to perform activities of daily life, living situation and general practitioner. Medical expenditure was assessed by retrieval of the general practice medical records and by recording all hospital and nursing home admissions, and all general practice and outpatient visits. Pharmaceutical consumption was recorded through the computerized records of the central pharmacy. Valid results were obtained for 44 pairs (91%) in the hip fracture and for 42 pairs (93%) in the vertebral fracture group. Cost of medical consumption in the year before the hip fracture was similar in patients and control subjects, but the incremental cost in the first year after the hip fracture was almost US$10 000. In the second year after hip fracture the incremental cost was still about $1000. Accounting for the excess mortality in hip fracture patients had little effect on cost in the first year, but cost in the second year was doubled to almost $2000. For vertebral fractures, we did not detect important acute care costs, but these fractures were associated with a yearly recurrent incremental cost of over $1000. However, almost half this difference was already present before the occurrence of the fracture, and was attributable to hospital admissions. The remainder of the incremental cost was mainly due to pharmaceutical consumption and to a lesser extent to admissions to orthopedic surgery wards. We conclude that hip fractures cause excess mortality and an important incremental cost especially during the first year, and that these could probably be avoided by prevention of hip fractures. For vertebral fractures we found no evidence of important acute care costs but we observed a yearly returning incremental cost. Part of this incremental cost, however, was pre-existing and might therefore by caused by co-morbidity. Received: 29 July 1998 / Accepted: 11 December 1998     

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     

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     

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     

Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women

Parathyroid hormone (PTH) is a new treatment for osteoporosis and has been shown to reduce the risks of vertebral and non-vertebral fractures in postmenopausal women in clinical trials. The objective of this study was to estimate the cost-effectiveness of teriparatide in addition to calcium and vitamin D, using a simulation model. The base case analysis was conducted for a cohort of 69-year-old women in Sweden who had at least one previous vertebral fracture and low bone mineral density. The model simulated the course of events in 6-month cycles in individual patients until death or 100 years of age. During each cycle the patients were at risk of experiencing clinical vertebral, hip or wrist fractures, or death. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Swedish data on fracture costs, utility reductions after fracture, fracture risks and mortality rates were used. The model incorporated new epidemiological evidence that indicates fracture risks and mortality rates are higher in the subsequent years post-fracture. The results showed that the cost-effectiveness of the treatment is highly dependant on the risk profile of the treated patients and the timing of starting treatment relative to previous fractures. The cost per QALY gained for treatment of a population of 69-year-olds with a T-score at the femoral neck of –3 was in the base case estimated to be between EUR (€) 20,000 and 64,000 for patients with a recent or historic vertebral fracture respectively. The study provides further evidence of the benefit and cost-effectiveness of starting osteoporotic treatments early in patients with a new fracture, and also that teriparatide may provide valuable clinical benefits for these patients and may be considered a cost-effective intervention when targeted to the appropriate patients.     

Improving Risk Assessment: Hip Geometry, Bone Mineral Distribution and Bone Strength in Hip Fracture Cases and Controls. The EPOS Study

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX ‘beta’ versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)²) and age were considered alongside femoral neck BMD (FN-BMD, g/cm²) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong’s test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more pro-active approach to identifying women at high risk of hip fracture in the community. Received: 16 March 2001 / Accepted: 3 August 2001     

The Effect of Alendronate on Fracture-Related Healthcare Utilization and Costs: The Fracture Intervention Trial

The Vertebral Fracture Arm (VFA) of the Fracture Intervention Trial (FIT) study demonstrated that alendronate reduced the incidence of spine, forearm and hip fractures in women with low bone mass and existing vertebral fractures by about 50%. The objective of the present study was to determine the effects of alendronate therapy versus placebo on fracture-related healthcare utilization and costs. Participants were randomly assigned to double-masked treatment with alendronate (5 mg/day for 2 years and then 10 mg/day for 1 year) or placebo for 3 years. For each patient experiencing a clinical fracture, we determined whether treatment in an emergency room, hospital, nursing home and/or rehabilitation hospital was a consequence of the fracture. The VFA of the FIT Study enrolled 2027 women aged 55–81 years with low bone mass and pre-existing vertebral fractures from population-based listings in 11 metropolitan areas of the United States. We measured (1) the proportion of patients who had any fracture-related healthcare event and (2) the estimated cost of fracture-related healthcare services. Alendronate significantly reduced the proportion of patients utilizing fracture-related healthcare (emergency room, hospital, rehabilitation hospital or nursing home) by 25% (p= 0.038). Alendronate significantly reduced the costs associated with hip-fracture-related care by 58%, or $181 per patient randomized (p= 0.036). The reduction in fracture-related total costs was 35% ($190 per patient randomized) in the alendronate group relative to the placebo group (p= 0.114). Alendronate thus not only reduces the incidence of clinical fractures and associated morbidity, but reduces the proportion of patients utilizing the associated healthcare resources. Received: 30 October 2000 / Accepted: 8 February 2001     

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     

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