Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden.

BACKGROUND AND PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

Primary arthroplasty is better than internal fixation of displaced femoral neck fractures: a meta-analysis of 14 randomized studies with 2,289 patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

No association between inhaled corticosteroids and whole body DXA in postmenopausal women.

PURPOSE: Postmenopausal women treated with corticosteroids are regarded as a high-risk group due to the effect of both natural bone loss and possible adverse effects of treatment with inhaled corticosteroids (IC). OBJECTIVE: To compare bone mineral density (BMD) in postmenopausal women exposed only to IC (IC group, n = 106) with that of BMD in women not exposed to corticosteroids (n = 124) and women exposed to oral and/or intra-articular injections in addition to inhaled corticosteroids (OC group, n = 31). The women were recruited from a population-based prospective cohort study. METHODS: Dual X-ray absorptiometry (DXA) technique was used to measure BMD in whole body, spine, pelvis and lower extremities. A health questionnaire and an interview about past and present medication use were used. RESULTS: The mean duration and dose of IC were 9.5 +/- 4.5 years and 615 microg daily. Whole body BMD did not significantly differ between the IC group (1.103 g/cm(2)) and the unexposed group (1.087 g/cm(2)). Within the IC group, BMD stratified for cumulative dose of IC, duration or current dose above or below 800 microg did not differ. Z-score BMD for tertiles did not differ when comparing the IC and OC groups. CONCLUSION: No difference in BMD was noted between postmenopausal women exposed to inhaled corticosteroids and unexposed controls nor was there any dose response relationship between inhaled corticosteroid therapy and BMD.

Какие фактические данные существуют в отношении профилактики остеопороза и скрининга с целью выявления этого заболевания?

Вашему вниманию предлагается синтезированный доклад Сети фактических данных по вопросам здоровья (СФДЗ), цель которого состоит в определении эффективности профилактики остеопороза и скрининга с целью выявления этого заболевания. Предлагаемый обзор фактических данных показывает, что эффективны несколько мер, такие, как умеренная физическая активность, прием в правильных дозах кальция и витамина D, прекращение курения и лекарственное воздействие в группах повышенного риска с целью профилактики остеопороза. В обзоре не выявлено каких-либо прямых доказательств того, что скрининг с целью выявления остеопороза способствует снижению числа случаев переломов, но показано, что имеются достаточно убедительные косвенные доказательства эффективности скрининга в выявлении женщин в постменопаузе, у которых низка минеральная плотность костной ткани, и возможности уменьшить риск переломов (запястья и позвоночника) в этой категории населения путем лечения остеопороза. Сеть фактических данных по вопросам здоровья (СФДЗ), работа которой была инициирована и координируется Eвропейским региональным бюро ВОЗ, представляет собой информационную службу для лиц, принимающих решения в области общественного здравоохранения и медицинской помощи, в Европейском регионе ВОЗ. СФДЗ может также быть полезна и другим заинтересованным сторонам.

What evidence is there for the prevention and screening of osteoporosis?

This is a Health Evidence Network (HEN) synthesis report seeking to determine the effectiveness of the prevention and screening of osteoporosis. The review of evidence shows that several measures, such as moderate physical activity, an appropriate intake of calcium and vitamin D, cessation of smoking and pharmaceutical intervention in high-risk groups for preventing osteoporosis are effective. The review found no direct evidence that screening for osteoporosis reduces fractures, but it shows that there is good indirect evidence that screening is effective in identifying postmenopausal women with low bone mineral density and that treating osteoporosis can reduce the risk of fractures (wrist and spine) in this population. HEN, initiated and coordinated by the WHO Regional Office for Europe, is an information service for public health and health care decision-makers in the WHO European Region. Other interested parties might also benefit from HEN.

Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.

UNLABELLED: 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 men. 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% CI, 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.

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

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.

Costs and quality of life associated with osteoporosis-related fractures in Sweden.

This prospective observational data collection study assessed the cost and quality of life related to hip, vertebral and wrist fracture 1 year after the fracture, based on a patient sample consisting of 635 male and female patients surviving a year after fracture. Data regarding resource use and quality of life related to fractures was collected by questionnaires at baseline, 4 months and 12 months. Information was collected by the use of patients' records, register sources and by asking the patient. Quality of life was estimated with the EQ-5D questionnaire. Costs were estimated from a societal perspective, including direct and indirect costs. The mean fracture-related cost the year after a hip, vertebral and wrist fracture were estimated, in euros (), at 14,221, 12,544 and 2,147, respectively [converted from Swedish krona (SEK) at an exchange rate of 9.1268 SEK/]. The mean reduction in quality of life was estimated at 0.17, 0.26 and 0.06 for hip, vertebral and wrist fracture, respectively. Based on the results, the yearly burden of osteoporosis in Sweden could be estimated at 0.5 billion (SEK 4.6 billion). The patient sample for vertebral fracture was fairly small and included a high proportion of fractures leading to hospitalization, but they indicate a higher cost and loss of quality of life related to vertebral fracture than previously perceived.

Orthopaedic treatment of displaced femoral neck fractures in elderly patients.

PURPOSE AND METHOD: A review article concerning orthopaedic treatment and rehabilitation of displaced femoral neck fractures, focusing on evidence-based knowledge. RESULTS: 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. CONCLUSION: 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.

Risk factors for hip fractures in a middle-aged population: a study of 33,000 men and women.

Knowledge about subjects who sustain hip fractures in middle age is poor. This study prospectively investigated risk factors for hip fracture in middle age and compared risk factors for cervical and trochanteric hip fractures. The Malmö Preventive Project consists of 22,444 men, mean age 44 years, and 10,902 women, mean age 50 years at inclusion. Baseline assessment included multiple examinations and lifestyle information. Follow-up was up to 16 years with regard to occurrence of fracture. One hundred thirty-five women had one low-energy hip fracture each, 93 of which were cervical and 42 trochanteric. One hundred sixty-three men had 166 hip fractures, of which 81 were cervical and 85 trochanteric. In the final Cox regression model for women, the risk factors with the strongest associations with hip fracture were diabetes (risk ratio (RR) 3.89, 95% confidence interval (CI) 1.69-8.93, p=0.001) and poor self-rated health (RR 1.74, 95%CI 1.22-2.48, p=0.002). A history of previous fracture (RR 4.76, 95%CI 2.74-8.26, p=0.0001) was also a significant risk factor. In men, diabetes had the strongest association with hip fracture (RR 6.13, 95%CI 3.19-11.8, p=0.001). Smoking (RR 2.20, 95%CI 1.54-3.15, p=0.001), high serum gamma-glutamyl transferase (RR 1.84, 95%CI 1.50-2.26, p=0.001), poor self-rated health (RR 1.49, 95%CI 1.06-2.10, p=0.02) and reported sleep disturbances (RR 1.52, 95%CI 1.03-2.27, p=0.04) were other significant risk factors. The strongest risk factor for hip fracture for both women and men in middle age was diabetes. Many risk factors were similar for men and women, although the risk ratio differed. The risk factor pattern for cervical versus trochanteric fractures differed in both men and women. The findings indicate that those suffering a hip fracture before the age of 75 have a shorter life expectancy, suggesting that hip fractures affect the less healthy segment of the population.

The economic cost of low back pain in Sweden in 2001.

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 1860 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 does not appear to have risen during the last 10-15 years.

Predictive value of BMD for hip and other fractures.

UNLABELLED: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans.

Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.

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.

Epidemiology of osteoporotic fractures.

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.