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Biomedical subjects

Olof Johnell

Publications and source records attributed to Olof Johnell.

At least 19 recordsLinked to original sources
PubMed2006

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.

Aged↗
PubMed2006

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.

Absorptiometry, Photon↗
PubMed2006

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.

Aged↗
PubMed2005

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.

Aged↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Female↗
PubMed2005

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.

Absorptiometry, Photon↗
PubMed2005

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.

Amino Acid Sequence↗
PubMed2005

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.

Adolescent↗
PubMed2004

Assessment of fracture risk.

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.

Adult↗
PubMed2004

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.

Absorptiometry, Photon↗
PubMed2004

A meta-analysis of milk intake and fracture risk: low utility for case finding.

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.

Adult↗
PubMed2004

Alcohol intake as a risk factor for fracture.

High intakes of alcohol have adverse effects on skeletal health, but evidence for the effects of moderate consumption are less secure. The aim of this study was to quantify this risk on an international basis and explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and 11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and the Rotterdam Study. Cohorts were followed for a total of 75,433 person-years. The effect of reported alcohol intake 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 included age and BMD. The results of the different studies were merged using weighted beta-coefficients. Alcohol intake was associated with a significant increase in osteoporotic and hip fracture risk, but the effect was nonlinear. No significant increase in risk was observed at intakes of 2 units or less daily. Above this threshold, alcohol intake was associated with an increased risk of any fracture (risk ratio [RR] = 1.23; 95% CI, 1.06-1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16-1.65), or hip fracture (RR = 1.68; 95% CI, 1.19-2.36). There was no significant interaction with age, BMD, or time since baseline assessment. Risk ratios were moderately but not significantly higher in men than in women, and there was no evidence for a different threshold for effect by gender. We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in case-finding strategies.

Adult↗
PubMed2004

Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men.

UNLABELLED: Based on data searches and life-table analyses, we determined the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture after sustaining a Colles' or spine fracture and searched for potential gender-related differences. In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. INTRODUCTION: Colles' fracture occurrence has been largely ignored in public health approaches to identify target populations at risk for hip fracture. The aim of this study was to estimate the long-term and short-term absolute risks of hip fracture after sustaining a Colles' or spine fracture and to search for potential gender-related differences in the relationship between fracture history and future fracture risk. MATERIALS AND METHODS: To determine the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture, we applied life-table methods using U.S. age- and sex-specific hip fracture incidence rates, U.S. age-specific mortality rates for white women and men, pooled hazard ratios for mortality after Colles' and spine fracture, and pooled relative risks for hip fracture after Colles' and spine fracture, estimated from cohort studies by standard meta-analytic methods. RESULTS: Our results indicate that the estimated remaining lifetime risks are dependent on age in both genders. In women, remaining lifetime risks increase until the age of 80 years, when they start to decline because of the competing probabilities of fracture and death. The same pattern is found in men until the age of 85 years, the increment in lifetime risk being even more pronounced. As expected, the risk of sustaining a hip fracture was found to be higher in postmenopausal women with a previous spine fracture compared with those with a history of Colles' fracture. In men, on the other hand, the prospective association between fracture history and subsequent hip fracture risk seemed to be strongest for Colles' fracture. At the age of 50, for example, the remaining lifetime risk was 13% in women with a previous Colles' fracture compared with 15% in the context of a previous spine fracture and 9% among women of the general population. In men at the age of 50 years, the corresponding risk estimates were 8%, 6%, and 3%, respectively. Similar trends were observed when calculating 5- and 10-year risks. CONCLUSIONS: In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. The gender-related differences reported in this analysis should be taken into account when designing screening and treatment strategies for prevention of hip fracture in men.

Age Factors↗