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Several previous studies have reported regional differences in the incidence of hip fractures. A population-based study was performed in the city of Malmo (urban population) and in the municipality of Sjobo (rural population), 60 km apart. A total of 961 men and women, randomly selected and of Scandinavian ethnic background, participated in the study. Bone mineral content (BMC) of the forearm was measured with single-photon absorptiometry (SPA). Women and men in the city had significantly lower BMC compared with the rural population. The differences were even more pronounced when comparing a true urban population (lived their entire life in a city) with a true rural population (never lived in a city). The differences in BMC between Malmo and Sjobo were more obvious in men. These data suggest that differences in bone mass between an urban and a rural population could to some extent explain differences in fracture incidence.

The aims of this study were to determine common international risk factors for hip fracture in women aged 50 years or more. We studied women aged 50 years or more who sustained a hip fracture in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey over a 1-year period. Women aged 50 years or more selected from the neighborhood or population registers served as controls. Cases and controls were interviewed using a structured questionnaire on work, physical activity, exposure to sunlight, reproductive, history and gynecologic status, height, weight, mental score, and consumption of tobacco, alcohol, calcium, coffee, and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), short fertile period, low physical activity. lack of sunlight exposure, low milk consumption, no consumption of tea, and a poor mental score. No significant adverse effects of coffee or smoking were observed. Moderate intake of spirits was a protective factor in young adulthood, but otherwise no significant effect of alcohol intake was observed. For some risks, a threshold effect was observed. A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Thus, about half of the hip fractures could be explained on the basis of the potentially reversible risk factors sought. In contrast, the use of risk factors to "predict" hip fractures had moderate sensitivity and specificity. We conclude that variations in lifestyle factors are associated with significant differences in the risk of hip fracture, account for a large component of the total risk, and may be of some value in selecting individuals at high risk.

Altogether 733 postmenopausal women were interviewed with regard to their age at menopause. Subsequent fragility fractures over an 11 year period were recorded. Fragility fractures had occurred in 212 women. These women had an earlier menopause, but the deviation from the nonfracture group was significant only in those who were less than 70 years at the beginning of the fracture catchment period. Women 50-69 years of age, in the lowest quartile of menopausal age, sustained 50% more fragility fractures than those in the highest quartile. In older women menopausal age does not predict fragility fractures. Women less than 70 with an early menopause had a significantly lower initial bone mass.

We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40-80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 +/- 3.6 microgram/l vs 8.2 +/- 4.2 microgram/l (p = 0.006)), after adjusting for age and BMC difference. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70-80 years with a fracture sustained during the previous 6 years, PICP was lower (128 +/- 32 microgram/l vs 144 +/- 34 microgram/l, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = -0.31, ICTP-age r = 0.44, ICTP-BMC r = -0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70-80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (P = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).

Summary A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. Introduction The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. Methods Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. Results Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m2) ranged from 0.2% at the age of 50 years for women without CRF’s to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. Conclusion The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.

Few economic or quality-of-life studies have investigated the long-term consequences of fragility fractures. This prospective observational data collection study assessed the cost and quality of life related to hip, vertebral, and wrist fracture 13-18 months after the fracture, based on 684 patients surviving 18 months after fracture.Data regarding resource use and quality of life related to fractures was collected using questionnaires at 7 research centers in Sweden. Information was collected using patient records, register sources, and by asking the patient. Quality of life was estimated using the EQ-5D questionnaire. Direct and indirect costs were estimated from a societal standpoint.The mean fracture-related cost 13-18 months after a hip, vertebral, or wrist fracture were estimated to be euro2,422, euro3,628, and euro316, respectively. Between 12 and 18 months after hip, vertebral, and wrist fracture, utility increased by 0.03, 0.05, and 0.02, respectively. Compared to prefracture levels, the mean loss in quality of life between 13 and 18 months after fracture was estimated to be 0.05, 0.11, and 0.005 for hip, vertebral, and wrist fracture.The sample of vertebral fracture patients was fairly small and included a high proportion of fractures leading to hospitalization, but the results indicate higher long-term costs and greater loss in quality of life related to vertebral fracture than previously believed.

Context: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Objective: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)n microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. Design and Study Subjects: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n ≅ 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5α-androstane-3α,17β-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. Results: In both cohorts, (TAAAA)n and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5α-androstane-3α,17β-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Conclusions: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.

The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. Introduction: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim Of this Study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly trien. Materials and Methods: In the Swedish part of the MrOS study (n = 2908, average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. Results:FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01.) and X-ray-verified vertebral fractures (OR, 2.00; 95% Cl, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. Conclusions: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required. (Less)

INTRODUCTION: It has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T-score should be taken for the purpose of diagnosing osteoporosis. PURPOSE: The aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination for fracture prediction. METHODS: We studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately. Results of the different studies were merged using weighted beta-coefficients. RESULTS: The gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined, the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI)=1.42-1.61] per standard deviation (SD) decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI=1.38-1.56). Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45-1.64). Higher gradients of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10-2.87), with lumbar BMD was 1.57 (95% CI=1.36-1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95% CI=1.81-2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of specificity. Thus, the same effect could be achieved by using a less stringent T-score for the diagnosis of osteoporosis. CONCLUSIONS: Since taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis of osteoporosis is low.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures. © International Osteoporosis Foundation and National Osteoporosis Foundation 2005.

The treatment of displaced femoral neck fractures has long been debated. 14 randomized controlled studies (RCTs) comparing internal fixation with primary arthroplasty may give material for evidence-based decision making.Computerized databases were searched for RCTs published between 1966 and 2004. 14 RCTs containing 2,289 patients were included in a metaanalysis regarding complications, reoperations and mortality. The analysis was performed with software from the Cochrane collaboration.Primary arthroplasty leads to significantly fewer major method-related hip complications and reoperations, compared to internal fixation. There was no significant difference in mortality between the two groups at 30 days and 1 year. Most of the studies found better function and less pain after primary arthroplasty.Primary arthroplasty should be used in most patients with displaced femoral neck fracture. The healthy, lucid individual, 70-80 years old, should be given a total hip arthroplasty. The older, impaired or institutionalized patient would benefit from a hemiarthroplasty.

The International Society for Clinical Densitometry (ISCD) has published position statements on topics relating to the use and interpretation of measurements of bone mineral density (BMD). The most recent appeared in the Journal of Clinical Densitometry (1) and was republished in the Journal of Endocrinology and Metabolism and in Osteoporosis International (2,3). The topics included the indications for testing with BMD, the use of central dual energy X-ray absorptiometry (DXA) for the diagnosis of osteoporosis, the use of the Z-score and some recommendations for the spelling of the T-score and Z-score. Although these topics were chosen in an attempt to produce international consistency and consensus, most of the position statements lack a scientific basis. (Less)

The objectives of the present study were to estimate 10-year probabilities of clinical vertebral fractures in women, according to age and bone mineral assessment using phalangeal quantitative ultrasound (QUS). Risks were computed from UK derived data on the incidence of a first symptomatic vertebral fracture and mortality rates for each year of age using Poisson models. The 10-year probability of vertebral fracture was determined as the proportion of individuals fracture-free at that site from the age of 45 years. We assumed that the risk of fracture increased with decreasing QUS as assessed by an independent re-analysis of a previously published, multicenter cross-sectional study. For amplitude-dependent speed of sound (AD-SoS) information was available from 8,502 women, and vertebral fracture risk increased 1.7-fold for each SD decrease in measurement. For fast wave amplitude (FWA), available in 6,573 women, the risk gradient was 2.4/SD. In a subset of the population ( n =1,572) in whom bone mineral density was measured at the lumbar spine, the gradient of risk was 2.3/SD, with similar gradients of risk noted for AD-SoS (1.8/SD) and FWA (2.6/SD). Ten-year probabilities increased with age and decreasing Z -score. The use of absolute risk permits information from different types of bone mineral measurements to be applied for the assessment of patients, either alone or in combination with other independent risk factors.

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.

A review article concerning orthopaedic treatment and rehabilitation of displaced femoral neck fractures, focusing on evidence-based knowledge.Properly performed randomized controlled studies comparing internal fixation and primary arthroplasty provides the best basis to decide which method should be used. During the last decade, several such studies have been published, in addition to a few earlier works. After internal fixation with pins, screws or sliding hip screw and plate, the failure rate was 21 - 57% and re-operations were performed in 14 - 53% of all the cases. In the studies using THA, the failure rate was 4 - 11% and the re-operation rate 2 - 8%. The corresponding numbers for hemi-arthroplasty were 3 - 23% and 0 - 24%. A primary arthroplasty tends to result in better function and less pain during the rehabilitation period.With support in evidence-based literature, an elderly patient with displaced femoral neck fracture should be treated with a primary arthroplasty. If the individual is healthy, active and mentally intact, a total hip arthroplasty should be performed, otherwise a hemi-arthroplasty. This rationale ensures fewer failures and re-operations, as well as better function and less pain during the rehabilitation.

Background Low back pain (LBP) is a common cause of lost work days and disability. In 2001, expenditure for back pain represented 11% of the total costs for short-term sick leave in Sweden, and about 13% of all early retirement pensions were granted for back problems, of which LBP is the most important symptom. The magnitude of LBP as a health problem justifies a closer look at its burden of illness to society.Materials and methods We assessed the costs of LBP to society in Sweden in 2001. The study was conducted in a cost-of-illness framework, measuring both the direct costs of providing health care to LBP patients, and the indirect costs as the value of the production that is lost because people are too ill to work. The costs were estimated by a prevalence and top-down approach.Results The total cost of LBP was 1 860 million EUR in Sweden in 2001. The indirect costs due to lost productivity accounted for 84% of the total cost.Interpretation The cost of illness due to low back pain was substantial, but d...

A low intake of calcium is widely considered to be a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the effect of age, gender and bone mineral density (BMD) on this risk. We studied 39,563 men and women (69% female) from six prospectively studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000 person-years. The effect of calcium intake as judged by the intake of milk on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture. There was no difference in risk ratio between men and women. When both sexes were combined there was a small but non-significant increase in the risk of osteoporotic and of hip fracture. There was also a small increase in the risk of an osteoporotic fracture with age which was significant at the age of 80 years (RR = 1.15; 95% CI = 1.02-1.30) and above. The association was no longer significant after adjustment for BMD. No significant relationship was observed by age for low milk intake and hip fracture risk. We conclude that a self-reported low intake of milk is not associated with any marked increase in fracture risk and that the use of this risk indicator is of little or no value in case-finding strategies.

The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.

The aim of this study was to find out whether a single bone mineral density (BMD) measurement performed at middle age in early postmenopausal women could predict future fragility fractures. The Malmo Preventive Project, a population-based cardiovascular prevention study, included a subgroup of 1294 women, mean age 53, on which forearm BMD measurements were made using single-photon absorptiometry (SPA). Risk ratios (RRs) were calculated for an age-adjusted decrease in BMD of one standard deviation. During the 9-yr follow-up, 65 women sustained 86 fractures. The data were analyzed with Cox's proportional hazard analysis. The relative risk for sustaining any fragility fracture were 2.02 (95% confidence interval [CI] = 1.56–2.61) and 1.62 (CI = 1.26–2.08) at the distal and proximal forearm BMD measurement, respectively. The risk increase was significant for forearm fracture at the distal BMD level (RR = 1.94; range=1.40–2.68) and at the proximal BMD level (RR = 1.77; range=1.29–2.42). Our study is one of the first to show that a BMD measurement in a population at age 50 can predict fracture over almost 10 yr, indicating that early identification of women with increased fracture risk is possible, and the cost-effectiveness of such an approach needs to be further evaluated.

Several osteoporotic fractures such as hip fractures have a very high morbidity and mortality, and there are similar new findings for vertebral fractures. There have been several definitions of an osteoporotic fracture, and recently updated definitions have specified fractures occurring at a site associated with low BMD and which increase in incidence after the age of 50 years. Other definitions are based on clinical diagnosis. Lifetime risk of any osteoporotic fracture is very high and lies within the range of 40-50% in women and 13-22% for men. Measuring the true burden of osteoporotic fractures involves multiplying the morbidity of hip fractures according to age group: for women aged 50-54 years, the disability caused by osteoporotic fractures is 6.07 times that accounted for by hip fracture alone, and for women aged 80-84 years, the incidence of hip fractures should be multiplied by 1.55; for men aged 50-54 years, the incidence of hip fractures should be multiplied by 4.48, and for those aged 80-84 years by 1.50.

Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

The aim of this study was to examine the effects of risedronate (5 mg/daily) in patients identified solely on the basis of a prior fragility fracture, without BMD as an inclusion criterion. A total of 1,802 patients were examined from the VERT-NA and VERT-MN clinical trials. Lateral radiographs (T4 to L4) were obtained at baseline and annually; incident fractures were evaluated using quantitative and semiquantitative methods at the central facility. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Secondary analyses evaluated vertebral fracture efficacy in patient subgroups categorized according to the presence of risk factors for osteoporosis at baseline (age, femoral neck BMD, lumbar spine BMD, more severe BMD, height, weight, body mass index, prevalent nonvertebral fracture status, smoking, and bone turnover marker levels). Over 3 years, risedronate reduced the risk of new vertebral fractures by 44% (95% CI, 28% to 56%) compared with placebo. In patients subgrouped according to the presence or absence of putative risk factors, the efficacy of risedronate was comparable across all groups (all treatment-by-non BMD subgroup interactions por =0.210). Adjustment for age, baseline BMD, and prevalent vertebral fractures on fracture risk gave results similar to the unadjusted analysis. In patients taking placebo, the incidence of new vertebral fracture was higher in several of the high-risk categories (elderly, T-scoreor = -2.5 SD). In conclusion, the findings of this study suggest that risedronate is effective in patients identified solely on the basis of a prior fragility fracture and that the efficacy of risedronate in the reduction of vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fracture.

The value of bone mineral density (BMD) measurements to stratify fracture probability can be enhanced in a case-finding strategy that combines BMD measurement with independent clinical risk indicators. Putative risk indicators include age and gender, BMI or weight, prior fracture, the use of corticosteroids, and possibly others. The aim of the present study was to develop a mathematical framework to quantify the impact of using combinations of risk indicators with BMD in case finding. Fracture probability can be expressed as a risk gradient, i.e. a relative risk (RR) of fracture per standard deviation (SD) change in BMD. With the addition of other continuous or categorical risk indicators a continuous distribution of risk indicators is obtained that approaches a normal distribution. It is then possible to calculate the risk of individuals compared with the average risk in the population, stratified by age and gender. A risk indicator with a gradient of fracture risk of 2 per SD identified 36% of the population as having a higher than average fracture risk. In individuals so selected, the risk was on average 1.7 times that of the general population. Where, through the combination of several risk indicators, the gradient of risk of the test increased to 4 per SD, a smaller proportion (24%) was identified as having a higher than average risk, but the average risk in this group was 3.1 times that of the population, which is a much better performance. At higher thresholds of risk, similar phenomena were found. We conclude that, whereas the change of the proportion of the population detected to be at high risk is small, the performance of a test is improved when the RR per SD is higher, indicated by the higher average risk in those identified to be at risk. Case-finding strategies that combine clinical risk indicators with BMD have increased efficiency, while having a modest impact on the number of individuals requiring treatment. Therefore, the cost-effectiveness is enhanced.

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Randomized, double-blind, controlled studies have shown that treatment with risedronate reduces the risk of vertebral fracture in postmenopausal women with established vertebral osteoporosis. They also show that the drug decreases the risk of non-vertebral fractures in women with osteoporosis. The aim of this study was to investigate the cost-effectiveness of risedronate in postmenopausal women with osteoporosis. A Markov model was applied to a UK setting. Treatment effects were computed by meta-analysis of randomized, controlled trials and given over 5 years to subjects aged between 60 and 80 years. Quality-adjusted life years (QALYs) and life years gained were used as outcome measures. Intervention with risedronate was cost-effective in women aged 60 years and older. Cost savings were also found for postmenopausal women aged 70 years and older with established vertebral osteoporosis (a prior spine fracture and BMD T-scoreor =-2.5 SD). This treatment was cost-effective for women aged 65 years and older who had a prior vertebral fracture and a BMD T-score at the threshold of osteoporosis ( T-score=-2.5 SD), and in women with a T-scoreor =-2.5 SD, but without a prior vertebral fracture. In women aged 60-80 years and at the threshold of osteoporosis ( T-score=-2.5 SD) but without a prior vertebral fracture, treatment exceeded the threshold for cost-effectiveness. However, if an additional, independent risk factor was assumed (e.g., corticosteroid use) treatment became cost-effective.

Background : One third of all the hip fractures occur in men. The risk for mortality following hip fracture is higher for men compared to women. The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures and increases bone mineral density (BMD) in osteoporotic women. Similar effects of alendronate were observed in men in some other trials. There are also results demonstrating alendronate to be cost-effective in the treatment of osteoporosis in women. Objective : To investigate the cost effectiveness of alendronate for male osteoporosis in Sweden by assuming the same relative risk reduction of fractures in men as for women, based on the FIT trial. Design : A Markov model earlier used to analyze cost effectiveness of alendronate in treatment of postmenopausal osteoporosis in Sweden was adapted to fit a cohort of Swedish men. Cost effectiveness of alendronate vs. no treatment was assessed by transitioning men in the model over time between different health states. Time horizon : The patients were followed from start of intervention until 100 years of age or death. In the base-case alendronate was assumed to have a fracture-risk-reducing effect for 10 years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. Results : Taking a societal perspective treating a 71-year-old man (mean age in the FIT) with low BMD and prior vertebral fracture (VFA) with alendronate was found to be associated with a cost of €14,843 per quality adjusted life year (QALY) gained. Conclusions : The results in this study indicate that treating osteoporotic men with alendronate was projected to be cost-effective, under the assumption of the same fracture-risk-reducing effect of alendronate for men as for women.

INTRODUCTION: The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy. We studied 2113 women > or = 75 years of age randomly selected from Sheffield, UK, and adjacent regions. Baseline assessment included hip BMD and clinical risk factors. Outcomes included death and fracture in women followed for 6723 person-years. MATERIALS AND METHODS: Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities. Women were categorized by fracture probability with and without a BMD assessment. A 10-year fracture probability threshold of 35% was taken as an intervention threshold. Discordance in categorization of risk (i.e., above or below the threshold probability) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification. Age, prior fracture, use of corticosteroids, and low body mass index were identified as significant clinical risk factors. RESULTS: A total of 16.8% of women were classified as high risk based on these clinical risk factors. The average BMD in these patients was approximately 1 SD lower than in low-risk women; 21.5% of women were designated to be at high risk with the addition of BMD. Fifteen percent of all women were reclassified after adding BMD to clinical risk factors, most of whom lay near the intervention threshold. When a high probability of reclassification was accepted (without a BMD test) for high risk to low risk (p1< or = 0.8) and a low probability accepted for low to high risk (P2 < or = 0.2), BMD tests would be required in only 21% of the population. CONCLUSION: We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD. BMD testing is required, however, in a minority of women--a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen. These findings need to be validated in other cohorts at different ages and from different regions of the world.

Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR] = 1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR = 1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR = 3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR = 1.2; 95% CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR = 1.6; 95% CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.

Global aging superimposed on existing infectious diseases and trauma will aggravate competition for health care resources to diagnose and treat osteoporosis. Efforts to implement public health measures are needed, but the targeted approach to assessment and treatment of high-risk individuals must also be refined. Increases in the elderly population worldwide will cause a dramatic rise in osteoporotic fractures, but other age-related diseases will increase as well. Changes will be superimposed on existing public health problems (e.g., malaria, alcoholism), and these acute health care needs will take priority in some areas. Societies in most parts of the world may have to limit osteoporosis control to broad public health measures, and such efforts (e.g., calcium and vitamin D supplementation) should be supported. In these regions, clinical decision-making will generally be limited to treating patients with fractures (who presumably have already failed any public health measures in place), or in a few wealthy countries, to patients with low bone density identified by case-finding. Case-finding approaches will vary with the resources available, although unselective (mass) screening by bone densitometry is largely ineffective and unaffordable anywhere. The key to clinical decision-making on behalf of individuals will be an assessment of absolute fracture risk, and the tools needed to predict the risk of an osteoporotic fracture over the next 10 years are now being developed. These include bone density measures, but also incorporate other risk factors (e.g., fracture history, corticosteroid use), which may allow extension of fracture risk prediction to nonwhite populations and to men. Even with a universal risk prediction tool, cost-effective treatment thresholds will vary by country based on the level of fracture risk in the region and on the resources available for health care. To better compete for these resources, efforts should be made to lower the cost of osteoporosis interventions. Additionally, evidence is needed that these interventions are really effective in reducing fractures in the community.

BACKGROUND. in this retrospective data base study, the authors sought to estimate direct costs for bone fractures in women age 65 years with early-stage breast carcinoma and to compare those costs with treatment costs for bone fractures in older women without early-stage breast carcinoma. METHODS. Direct costs for bone fractures in patients with early-stage breast carcinoma, which consist of excess treatment costs for bone fracture and excess costs of long-term care for bone fracture, were evaluated by using the 1997-1998 Standard Analytical File. The statistical significance of the difference in inpatient costs, medical treatment costs, and long-term care admission rates were determined with the t test and the Fisher chi-square test, respectively. RESULTS. For older women with early-stage breast carcinoma, the direct costs for bone fracture were estimated at $45,579, and 57% of those costs came from treating the bone fracture (32% came from inpatient hospital costs, and 25% came from noninpatient hospital costs), 25% came from other excess treatment costs, and 18% came from excess long-term care costs. The women who had early-stage breast carcinoma and sustained bone fracture did not differ significantly from the women without early-stage breast carcinoma who sustained a bone fracture. CONCLUSIONS. Bone fracture was associated with high direct costs in older women with early-stage breast carcinoma. Additional research should include appropriate, incidence-based studies to investigate the potential benefit of an intervention for preventing bone fracture in this increasingly large patient population. (Less)

An excess mortality is well described after vertebral fracture. Deaths are in part related to co-morbidity, but could also be due to the fracture event itself, either directly or indirectly. The aim of this study was to examine the quantum and pattern of mortality following vertebral fracture. We identified 16,051 men and women aged 50 years or more with a vertebral fracture that required hospitalization in 28.8 million person years from the patient register of Sweden. Mortality after vertebral fracture was examined using Poisson models applied to fracture patients and compared to that of the general population. At all ages, the risk of death was markedly increased immediately after the event. After a short period of declining risk, the risk increased with age at a rate that was higher than that of the general population and comparable to that 1 year after hip fracture. The latter function was assumed to be due to deaths related to co-morbidity and the residuum assumed to be due to the vertebral fracture. Causally related deaths comprised 28% of all deaths associated with vertebral fracture (depending on age). We conclude that a minority of deaths following hospitalization for vertebral fracture are attributable to the fracture itself under the assumptions we used.

The aim of this study was to examine the pattern of fracture risk following a prior fracture at the spine, shoulder or hip. We studied 1918 patients with fractures at these sites identified from the Department of Radiology in Malmo who were followed for 5 years. Poisson regression was used to compute fracture rates immediately after the initial fracture and at 5 years thereafter in men and women aged 60 or 80 years. Immediate fracture risk was higher than that of the general population, more markedly so at the age of 60 than at 80 years. At the age of 60 years, the risk of hip, forearm and spine fractures were significantly increased following a prior spine, hip or shoulder fracture in men. A similar pattern was seen in women, except that the increase in risk of forearm fracture following a spine or hip fracture was not statistically significant. The incidence of further fractures at the shoulder, spine or hip fell with time after the first fracture, a fall that was significant for all fractures after a shoulder fracture, hip fracture after a spine fracture, and hip and spine fractures after a hip fracture. We conclude that the risk of a subsequent fracture immediately after an osteoporotic fracture is highest immediately after the event. This provides a rationale for very early intervention immediately after fractures to avoid recurrent fractures.

We studied the appearance and frequency of the medial epiarticular osteophyte in human femoral heads. Specimens were sampled from 24 men and 31 women who underwent total hip arthroplasty. On radiography, medial epiarticular osteophytes were present in two thirds of the cases. However, histological examination revealed endochondral ossification in all. Presumably, the bone formation was preceded by the formation of canals and cavities containing vessels. Due to the ossification around these canals and cavities, the histological picture frequently featured two layers of cartilage with bone in the middle. Also in the marginal osteophytes, bone was formed by endochondral ossification. However, this bone appeared more irregular. The new bone formation most likely indicates a reactivated growth as an attempt to repair the osteoarthritic lesions rather than a process of degradation.

Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.

The quality of the subchondral bone in total knee arthroplasty (TKA) may be important for the outcome. We correlated a histomorphologic analysis of the prosthetic bone bed to micromotion as analyzed by roentgen stereophotogrammetric analysis (RSA). Twenty-three knees, both osteo- and rheumatoid arthritic were studied. The mean migration after 1 year was 1 mm (0.21–2.68), with no correlation to the bone variables or diagnosis. One patient underwent revision after 3 years because of pain. One patient underwent revision after 15 years because of aseptic loosening. This patient appeared stable according to changes in maximum total point motion (MTPM), but the prosthesis migrated continuously according to segment motion. Prosthetic migration increased after 10 years, zones started to evolve, and the patient became symptomatic after 13 years. A biopsy of the bone bed was taken in all patients. A larger percentage of trabecular bone and a larger relative area of unmineralized osteoid surface were found in patients with rheumatoid arthritis compared with those with osteoarthritis. The latter finding is probably a result of increased bone turnover. In conclusion, no support currently exists for the idea that preoperative bone quality, evaluated as bone histomorphometry, has any impact on prosthetic micromotion in knee prostheses.

A high excess mortality is well described after hip fracture. Deaths are in part related to comorbidity and in part due directly or indirectly to the hip fracture event itself (causally related deaths). The aim of this study was to examine the quantum and pattern of mortality following hip fracture. We studied 160,000 hip fractures in men and women aged 50 years or more, in 28.8 million person-years from the patient register of Sweden, using Poisson models applied to hip fracture patients and the general population. At all ages the risk of death was markedly increased compared with population values immediately after the event. Mortality subsequently decreased over a period of 6 months, but thereafter remained higher than that of the general population. The latter function was assumed to account for deaths related to comorbidity and the residuum assumed to be due to the hip fracture. Causally related deaths comprised 17-32% of all deaths associated with hip fracture (depending on age) and accounted for more than 1.5% of all deaths in the population aged 50 years or more. Hip fracture was a more common cause for mortality than pancreatic or stomach cancer. Thus, interventions that decreased hip fracture rate by, say, 50% would avoid 0.75% or more of all deaths.

The prevalence of vertebral deformity, estimated in lateral spine radiographs (Th4-L4) using quantitative morphometry, in 64 men and 132 women with hip fractures was compared with the prevalence of vertebral deformity in individuals in two population-based studies. A vertebral deformity of a specific vertebra was defined as a 3, 4, or 5 SD reduction from the normal mean of any of three ratios describing that specific vertebra. The age-adjusted prevalence of individuals with vertebral deformities was higher among the hip fracture patients than among the reference subjects in both genders, with an odds ratio of 3.6 [95% confidence interval (CI) 1.9-6.6] in men and 2.6 (95% CI 1.7-4.1) in women using deformity criterion -3 SD. Also, the number of vertebrae with deformities (-3 SD) in individuals with one deformity or more was greater among the hip fracture patients than among the reference subjects (in men mean 2.3 versus 1.8, P = 0.007; in women mean 3.3 versus 2.0, P0.001). Adjusted for age there were more vertebrae with deformities (-3 SD) among female than among male hip fracture patients (mean 3.3 versus 2.3, P = 0.01). We found no differences in the vertebral deformity rates when comparing patients with a per- or subtrochanteric hip fracture with patients with a cervical hip fracture. In conclusion, there is a relationship between vertebral deformities and hip fractures suggesting that a prevalent vertebral deformity could predict an increased hip fracture risk.

The Fracture Intervention Trial (FIT) demonstrated that the bisphosphonate alendronate reduces the risk of hip, spine and wrist fracture in osteoporotic women by approximately one half.To use data from FIT to conduct a cost-effectiveness analysis of alendronate.A Markov model was developed for a cohort of Swedish women, comparable in relative fracture risk to the women enrolled in the FIT vertebral fracture arm (i.e. age 71 years with low bone mass plus at least one prior spine fracture). The women in the model (with low bone mass and a previous spine fracture) were exposed to alendronate therapy and transitioned over time from a 'well' health state to health states of 'hip fracture', 'spine fracture', 'wrist fracture' or 'death'. All costs were calculated in 2000 Swedish kronors (SEK).In the Markov model our base-case treatment duration was 5 years followed by a 5-year period where the benefit declined linearly to 0.We found that treating 71-year-old osteoporotic women with a prior spine fracture with alendronate resulted in a cost per quality-adjusted life-year (QALY) gained of SEK76000, which is well below the threshold for cost effectiveness of SEK300000. For women aged 65 years, the cost-effectiveness ratio increased to SEK173000 and for women aged 77 years, the cost-effectiveness ratio decreased to SEK52000.Treating older osteoporotic women with alendronate was more cost effective than treating younger women with osteoporosis, and treating osteoporotic women with prior spine fracture was more cost effective than treating osteoporotic women without prior spine fracture. However, the costs per QALY gained for all populations studied were below generally accepted thresholds for cost effectiveness.

We included in a prospective, randomized study 68 patients aged 70 years or older, with displaced cervical hip fractures. The patients were randomized to internal fixation with hook-pins (36) or primary arthroplasty (32) (total or hemiarthroplasty due to their prefracture status) and followed for 2 years. Patients with rheumatoid arthritis, mental confusion and/or residence in an institution were excluded. The postop- erative stay in hospital, rehabilitation wards or nursing homes were recorded as well as complications and the costs of surgery. The aim of this study was to compare the accumulated costs of each method, during the first 2 years after the fracture. In the internal fixation group, 15/36 were considered failures, as compared to 1/32 in the arthroplasty group. As regards primary treatment of the fracture, the dura- tions of surgery and hospital stay were shorter after internal fixation, but the total need for hospitalization/ institutionalizaion was somewhat longer in these patients. The mean 2-year cost for a patient with inter- nal fixation was USD 21,000 and of one with primary arthroplasty USD 15,000. We conclude that primary arthroplasty is a cost- efficient treatment. Considering the very much higher failure rate after internal fixation—leading to increased suffering for these patients—primary arthroplasty stands out as the best method for displaced fractures of the femoral neck. 

This study evaluates the effect on the skeleton of physical activity from age 9 to 16. In 42 girls and 44 boys, bone mass and bone size were evaluated longitudinally by dual-energy X-ray absorptiometry (DXA) from ages 13 to 16. Physical activity from ages 9 to 13 was cross-sectionally evaluated at baseline (age 13). Girls with high physical activity from ages 9 to 13 at baseline had higher femoral neck bone mineral content (FN BMC; g) (P = 0.07), higher FN areal bone mineral density (FN aBMD; g/cm2), and higher FN volumetric BMD (FN vBMD; g/cm3) (both P < 0.05) compared with girls of low activity. FN width (cm) and head aBMD (an unloaded region) showed no differences when comparing the two groups. Three years of further high and low activity (from ages 13 to 16) did not yield any increased differences between the two groups. Boys with high physical activity from ages 9 to 13, had at baseline higher FN BMC, FN aBMD, and FN width (all P < 0.05) compared with boys with low activity. FN vBMD and head aBMD showed no differences when comparing the two groups. Three years of further high and low activity did not yield any increased differences between the two groups. We conclude that exercise may yield skeletal benefits before age 13, and that 3 years of continued high or low level activity up to age 16 did not yield any increased differences in bone size or bone mass in either girls or boys.

The aim of this study was to determine the threshold of fracture probability at which interventions become cost-effective. We modeled the effects of a treatment costing $500/year, given for 5 years, that decreased the risk of all osteoporotic fractures by 35%, followed by a waning of effect for 5 years. Sensitivity analyses included a range of effectiveness (10%-50%) and a range of intervention costs (200-500 dollars/year). Data on costs and risks were from Sweden. Costs included direct costs and costs in added years of life, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of 60,000 dollars per quality-adjusted life-year (QALY) gained was used. Costs of added years were excluded in a sensitivity analysis for which a threshold value of 30,000 dollars per QALY was used. In the base case, intervention was cost-effective when treatment was targeted to women at average risk at age of >or=65 years. Irrespective of the efficacy modeled (10%-50%) or of cost of intervention (200-500 dollars/year) segments of the population at average risk could be targeted cost-effectively: The lower the intervention cost and the higher the effectiveness, the lower the age at which intervention was cost-effective. With the base case (500 dollars/year; 35% efficacy) treatment in women was cost-effective with a 10 year hip fracture probability that ranged from 1.4% at the age of 50 years to 4.4% at the age of 65 years. The exclusion of osteoporotic fractures other than hip fracture would increase the threshold to a 9%-11% 10 year probability because of the substantial morbidity from fractures other than hip fracture, 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 cost-effectively targeted to individuals at moderately increased risk.

There is a need for studying the effects of long-term inhaled corticosteroid therapy on bone mineral density (BMD) and vertebral fracture rates in patients with mild chronic obstructive pulmonary disease (COPD).Patients (n=912, mean age 52 yrs) with mild COPD (mean forced expiratory volume in one second (FEV1) 77% of predicted; mean FEV1/slow vital capacity ratio 62%) were randomized to receive budesonide 400 mug, or placebo twice daily via Turbuhaler R. BMD was measured at the L2-L4 vertebrae and the femoral neck, trochanter and Ward's triangle by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24 and 36 months (n=161). Radiographs of the thoracic and lumbar spine were obtained at the beginning and end of treatment (n=653).Previous fractures were present at baseline in 43 budesonide-treated patients (13.4%) and 38 placebo-treated patients (11.5%). New fractures occurred in five budesonide-treated patients, compared with three in the placebo group (p=0.50). There were no significant changes in BMD at any site in budesonide-treated patients. compared with the placebo group, during the course of the study. Budesonide treatment was associated with a slight but statistically significant decrease in the area under the concentration-time curve for serum osteocalcin.In the present study, involving a large group of patients with chronic obstructive pulmonary disease, long-term treatment with budesonide 800 mug.day(-1) via Turbuhaler R had no clinically significant effects on bone mineral density or fracture rates.

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate since proven treatments are available. In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves.

Background: Surgical removal of the stomach (gastrectomy, Gx) induces osteopenia. In this study we compared the osteopenic effect of Gx with that induced by calcium (Ca) deficiency. Methods: Young male rats were subjected to Gx and/or low Ca diet (-Ca). A group of Gx rats received standard diet + oral Ca supplementation (+ Ca). The rats were killed at various times after the operation/start of treatment (longest time 12 weeks). After 8 weeks on low Ca diet, the blood Ca 2 concentration was lowered slightly in both Sham-operated and Gx rats. The calvariac were subjected to transillumination analysis and quantitative histomorphometry. Also the tibiae were subjected to histomorphometry. Results: Transillumination of the calvariae revealed extensive bone loss in the rats that had been subjected to Gx and/or low Ca diet, Gx + Ca induced the same bone loss as Gx alone. These observations were later confirmed in quantitative terms by histomorphometry (Sham-Ca 56%, Gx 35%, Gx + Ca 32%, Gx - Ca 58% less bone area than in Sham). The osteopenia induced by Gx+ low Ca diet seemed more rapid in onset than that induced by Gx or low Ca diet alone. Tibiae from Gx rats and rats given a low Ca diet displayed a reduced trabecular bone volume (Sham-Ca 27%, remaining, Gx 36%, Gx + Ca 44%, Gx - Ca 1711) and reduced trabecular number (Sham-Ca 44% remaining, Gx 41%, Gx + Ca 56%, Gx - Ca 33%). The trabecular thickness was reduced in the Gx rats and Gx - Ca rats (Gx 78% remaining, Gx-Ca 63%) but not in Sham-operated rats receiving a low Ca-dict (95% remaining). Conclusion: Although the pattern of osteopenia was qualitatively quite similar in Gx rats and Ca-deficient rats, in quantitative terms the low Ca diet was more detrimental to bone than Gx. Ca deficiency induced a similar degree of osteopenia in both Sham and Gx rats. Ca supplementation failed to prevent the Gx-induced osteopenia. (Less)

Interpretation of data in epidemiological cohort studies may be confounded if differences exist between non-participants and participants. In the Malmo part of the European Vertebral Osteoporosis Study (EVOS), which was designed to evaluate the prevalence of vertebral deformity in 50-80-year-old persons, we compared 74 men and 95 women who had been invited, but declined to participate with age- and gender-matched participants as regards alcohol abuse, previous fractures and subsequent mortality, factors known to affect the prevalence of vertebral deformity. We found more men with alcohol abuse, more men with a previous fragility fracture and a tendency to more men with a previous clinical vertebral fracture among the non-participants than in the male partici- pants. In contrast, there were fewer female non-partici- pants than female participants with a previous clinical vertebral fracture. The mortality rate during the decade after the baseline examination was higher among both male and female non-participants. The "true" prevalence of vertebral deformity in the whole male population at risk in Malmo seems to be underestimated in the EVOS study. In women, it is more dife cult to estimate the combined result of the confounding factors. Conclusions based on the EVOS participants may not be applicable to the whole popula- tion at risk. n

By combining data from the Discharge registers and the census bureaus in The Netherlands and Sweden, we calculated the age-specific incidences of primary total hip replacement (THR), studied the demographic profile of the population receiving THR and predicted demands. In the period 1986-1997, the number of THRs increased by 20% in Sweden to 10,000 operations (113/100,000 inhabitants) and by 68% to 17,400 operations (112/100,000 inhabitants) in The Netherlands. Of this increase 3% and 15% could be explained by changes in the age-profile and size of the population, respectively. Although the overall incidence of THR was similar in both countries in 1997, we found that, after correction for differences in population structure, the incidence of THR was 20% higher in The Netherlands. In Sweden, relatively more men were operated on than in The Netherlands. We also found that in Sweden, but not in the Netherlands, relatively more older people were operated on in 1997 than in 1987. Assuming no further change in the age- and sex-specific arthroplasty rates, the predicted annual number of total hip replacements by the year 2020 will increase by at least one fourth in Sweden and almost one half in The Netherlands.

Incident vertebral deformities are commonly defined by observed changes in height between measurements on two consecutive radiographs. However, conventional radiographs are subject to magnification, and this magnification may differ between films, leading to artifactual changes in height. In order to minimize this effect, it is common practice to record the spine-film and film-focus distances, and from this to calculate a magnification factor for each film. We present a simple statistical method for correcting for differences in magnification between two films if the spine-film and film-focus distances are unknown. This method is shown to reduce the variance of the magnification differences in vertebral heights by 14%, considerably more than is possible using the spine-film distance. Using the statistical method, the number of vertebrae that showed not only a reduction in one or more height of 15%, but were also judged clinically to be free from any incident deformity by an expert radiologist, was reduced from 100 to 46. The number showing a reduction of 20% that were judged fracture-free was reduced from 15 to 9. In the subset of subjects for whom the spine-film distance was known, the reduction in false positives was similar, whichever method was used to correct for magnification. There was no difference in the number of confirmed incident fractures detected when magnification correction by either method was employed. It is concluded that correcting for magnification differences using the statistical method outlined here reduces the number of false positive deformities very substantially and by a similar extent as correcting the magnification using reliable, measured spine-film and film-focus distances. A further advantage of this method is that it can be used retrospectively.

This review examines the hypothesis that there are gender differences in the relationship between bone mineral density (BMD) and fracture risk. Prospective studies of spine and hip fracture risk drawn from population samples suggest that the fracture risk increases as BMD decreases in men in the same way as that described in women. Moreover, for any given BMD at the spine, heel, or proximal femur the risk in men is similar to that in women. Although data are limited, prior fragility fractures increase subsequent fracture risks in both men and women. These studies suggest that the same BMD criteria used to diagnose osteoporosis in women can be applied to men.

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.