Search

The aim was to test the hypothesis that the human leucocyte antigen (HLA) haplotype that is not inherited from the mother, that is, the non-inherited maternal antigen (NIMA) affects the risk for type 1 diabetes (T1D). A total of 563 children with T1D and 286 non-diabetic control children from Sweden were genotyped for DRB1, DQA1 and DQB1 alleles. The frequency of positively (DR4-DQA1*0301-B1*0302 and DR3-DQA1*0501-B1*0201), negatively (DR15-DQ A1*0102-B1*0602) or neutrally (all other) T1D associated HLA haplotypes were compared between NIMA and non-inherited paternal antigen (NIPA). All comparisons were carried out between HLA-matched patients and controls. The frequency of positively associated NIMA was higher among both DR4/X-positive healthy individuals compared wit DR4/X-positive patients (P < 0.00003) and DR3/X-positive healthy individuals compared with DR3/X-positive patients (P < 0.009). No such difference was observed for NIPA. High-risk NIMA was increased compared to NIPA among healthy DR3/X- and DR4/X-positive children (P < 0.05). There was no difference in frequency of positively associated haplotypes between patient NIMA and NIPA. The NIMA but not the NIPA affects the risk for T1D, suggesting that not only the inherited but also non-inherited maternal HLA haplotypes, perhaps through microchimerism or other mechanisms, may influence the risk for the disease.

Hip fracture is associated with high early mortality. Little is known about long-term survival and subsequent fracture risk. The aim of this study was to evaluate survival and fracture risk after hip fracture in women at different ages. All women suffering a hip fracture during 1984-1985 in Malmö, Sweden, were identified (n = 766) and followed up to 22 yr or death. All new radiographic examinations related to musculoskeletal trauma with or without fracture were registered. Survival (mortality) and fracture was evaluated in 5-yr age bands and in age groups (75, 75-84, andor = 85 yr). Mean age was 79.6 +/- 9.9 yr (range, 31.6-99.4 yr), with 42% between 75 and 85 yr of age. Overall 22-yr survival was 6%: 79% at 1 yr, 48% at 5 yr, and 33% at 10 yr (i.e., population at risk). One-year mortality was 7%, 21%, and 33% for75, 75-84, andor = 85 yr of age, respectively, and 95% of thoseor = 85 yr were dead at 10 yr. Prior hip fracture did not affect age-adjusted mortality (OR, 1.05; 95% CI, 0.756-1.20; p = 0.15). A total of 768 fractures were registered at 715 occasions in 342 women (45%; mean, 2.3 fractures/woman; range, 1-11 fractures/woman). Of the fracture occasions, 15% occurred within the first year, 27% within 2 yr, and 73% within 5 yr. The residual lifetime fracture risk was 45%, with a mortality-adjusted increase to 86%. The 10-yr fracture risk was 40%; with a mortality-adjusted increased to 65%. In conclusion, almost one half of all women with a hip fracture suffer a new fracture during their remaining lifetime. Fracture risk is highly dependent on age and survival, emphasizing that preventive strategies need to be tailored to each age group specifically.

Background: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. Methods: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. Findings: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. Conclusion: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.

Musculoskeletal conditions are an increasingly common problem across the globe due to increased longevity and increased exposure to risk factors such as obesity and lack of physical activity. The increase is predicted to be greatest in developing countries, and there is thus an urgent need for the implementation of strategies and policies that will prevent and control these conditions. The ideal is modification of the risk factors in the whole community, and this will have wide-ranging health benefits as these risk factors are common to other major conditions. Changing people's behaviour is a challenge; targeting those at highest risk is potentially more effective, providing that there are both affordable ways of identifying those at risk and affordable interventions. Early intervention in those with a condition such as rheumatoid arthritis is probably the most cost-effective approach, but requires diagnostic capacity – in clinical skills and/or technology – as well as access to care. There is now much evidence for what can be achieved, but the challenge is how to implement these different strategies in developing countries where there are competing priorities for limited resources. The key strategy is to raise awareness among the public, health professionals, and policy makers of the importance of musculoskeletal health, of what can be achieved by prevention and treatment, and to ensure that policies reflect this. It is also necessary to educate the public to know when to seek care, and health-care workers to recognize the early signs of musculoskeletal conditions.

One of the important challenges in the management of osteoporosis is to identify women who are at high risk of developing osteoporosis and fragility fractures.Our objective was to evaluate whether assessment of bone metabolism at multiple occasions can identify women with the highest risk for bone loss.The Malmö Osteoporosis Prospective Risk Assessment study is an ongoing longitudinal study. Participants have been evaluated at baseline and after 1, 3, and 5 yr.We conducted a population-based study.Participants included 1044 women, all 75 yr old at baseline.Seven bone turnover markers were assessed at baseline and at 1, 3, and 5 yr (n = 573). The 5-yr change in areal bone mineral density (aBMD) was also determined.Baseline markers correlated weakly to change in total body aBMD. The associations were more pronounced when the average of the baseline and 1-yr measurements was used (standardized regression coefficients -0.12 to -0.23, P0.01). Adding the 3-yr and 5-yr measurement further strengthened the correlation (regression coefficients up to -0.30, P0.001). Women with constantly high turnover lost significantly more bone at total body assessment (-2.6%) than women with intermediate (-1.6%) or low turnover (-0.2%, P for trend0.001). They also had a greater decrease in hip BMD (-8.3, -6.0, and -5.1%, respectively, P = 0.010). Results were similar also in the subgroup of women with osteopenia.Our results suggest that serial assessment of bone turnover improves the identification of women with the highest rate of bone loss and osteoporosis risk.

Aims: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose and high 2-h glucose during an oral glucose tolerance test indicate impaired glucose tolerance or diabetes. The associations among fasting blood glucose, 2-h glucose, and the risk of fracture were investigated. Methods: The Malmö Preventive Project consists of 22,444 men (44 ± 6.6 yr) and 10,902 women (50 ±7.4 yr), with a follow-up of 19 yr (±3.9) and 15 yr (±4.5) for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, body mass index (BMI), and smoking. Results: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter in women (third and fourth quartile), adjusted for age, BMI, and smoking, was significantly associated with a decreased risk of multiple fractures, in men [odds ratios (ORs) 0.57–0.71] and women (ORs 0.38–0.66). In women, a 2-h glucose measurement above 7.5 mmol/liter was associated with a decreased risk of osteoporotic fractures (OR 0.57, 95% confidence interval 0.44–0.74). Conclusions: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.

Objectives: Osteoporosis is a known complication of rheumatoid arthritis (RA). This prospective study aimed to evaluate whether disease activity, disability, and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone mineral density (BMD). Methods: We followed 97 women (mean age 58 years), for 24 months, with a history of RA of less than 12 months. At baseline, 77 women were receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs) and 20 were receiving no treatment. Risk factors for osteoporosis were recorded. Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and medications were registered at baseline and every 6 months and calculated as areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at baseline and after 2 years and compared to BMD in age- and gender-matched controls. Risk factors were analysed by linear regression models. Results: BMD loss was comparable to that of age-matched women in both the lumbar spine and the femoral neck, although neither was significantly different from baseline. In multivariate analyses the AUC for DAS28 was an independent predictor of changes in lumbar spine BMD (p=0.003) and that for HAQ of changes in femoral neck BMD (p=0.018). GC use was not an overall predictor of BMD loss. Conclusion: BMD loss was predicted by high disease activity and disability but not by GC treatment. With the DMARD, GC, hormone replacement therapy (HRT), and bisphosphonate treatment strategies used during the study period, the general outcome seems favourable concerning loss of BMD in patients with early RA.

Musculoskeletal problems are very common, and clinical assessment is central to their appropriate management; however, many clinicians are not sufficiently competent to carry out this assessment. A standardized approach to the clinical assessment of a musculoskeletal problem is, therefore, necessary, whether the patient is presenting to primary care, rheumatology or orthopedics. Such a standardized approach gives a benchmark for this competency and can also be used as a teaching aid. As doctors become increasingly competent in clinical assessment and reach into training programs within musculoskeletal specialities, more detailed information will be required from the medical history of the patient, in addition to the use of special tests on clinical examination. These clinical skills need to be taught and also assessed.

Background and purpose Fractures can be prevented if osteoporosis is identified and treated. Starting in 2002, we have been using a screening program in which patients between 50 and 75 years of ag...

We invited 1604 randomly selected women, all 75 years of age, to participate in a study on the risk factors for fracture. The women were divided into three groups consisting of 1044 (65%) who attended the complete study, 308 (19%) respondents to the study questionnaire only and 252 (16%) who did not respond. The occurrence of the life-time fracture was ascertained from radiological records in all groups and by questionnaires from the attendees and respondents. According to the radiological records, fewer of the questionnaire respondents (88 of 308, 28.6%) and non-respondents (68 of 252, 27%) had sustained at least one fracture when compared with the attendees (435 of 1044, 41.7%; chi-squared test, p < 0.001). According to the questionnaire, fewer of the respondents (96 of 308, 31.1%) had sustained at least one previous fracture when compared with the attendees (457 of 1044, 43.7%; chi-squared test, p < 0.001). Any study concerning the risk of fracture may attract those with experience of a fracture which explains the higher previous life-time incidence among the attendees. This factor may cause bias in epidemiological studies.

Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p

Information on objectively assessed physical activity in elderly people is scarce. The aim of this study was to investigate accelerometer measures in elderly women, and its relation to other indices of physical activity and bone density. A subset of 57 women, all 80 years old, (range 80.0-80.7) of the Malmö OPRA study was equipped with an MTI accelerometer for a period of 5-7 days. A 7-day activity log was used. At baseline a self-assessment questionnaire was used and isometric muscle strength (knee), gait speed, balance and bone density measurements [dual-energy X-ray absorptiometry (total body, hip, and spine), and quantitative ultrasound of the calcaneus] were measured. About 14% (8 out of 57) had a moderate to vigorous physical activity (MVPA) (1,952 counts per min [CPM]) exceeding 30 min/day. The median CPM was 18. When compared to questionnaire data, the correlation between MVPA and physical activity was 0.50 (P0.001). The corresponding result for CPM was 0.48, P0.001. When compared to the activity log, the correlation between MVPA and physical activity away from home was 0.49 (P0.001). The corresponding result for CPM was 0.55, P0.001. The correlation between MVPA and gait speed was 0.41 (P = 0.002). The corresponding result for CPM was 0.40, P = 0.002. There were no correlations to the measurements of muscle strength, balance or bone density (all Por = 0.07). Accelerometers can be used for measuring of physical activity also of the elderly. Questions on daily physical activity correlated modestly with accelerometer results in elderly women. Accelerometer results were not correlated to measures of balance, muscle strength and bone density.

Bone morphogenetic protein-2 (BMP2) plays a key role in bone formation and maintenance. Studies of polymorphisms within the gene in relation to bone mineral density (BMD) and fracture have been inconsistent. Our aim was to investigate associations between polymorphisms in the BMP2 gene and bone mass, fracture, and quantitative ultrasound (QUS) measures at different stages of skeletal development. Study subjects were participants of two population-based cohorts of Swedish women: the PEAK-25 cohort of young adult women aged 25 years (n = 993) and the OPRA cohort of elderly women aged 75 years (n = 1,001). We analyzed four single-nucleotide polymorphisms (SNPs) across the BMP2 gene including the Ser37Ala SNP previously identified in relation to BMD, QUS of the calcaneus, and, in the elderly women, fracture. BMP2 gene variations were associated with QUS of bone, independent of BMD, but only in the young women. Even after adjusting for confounding factors, SNP rs235754 in the 3' region of the gene was significantly associated with the ultrasound parameters speed of sound (P = 0.003) and stiffness (P = 0.002). The 5' SNP rs235710 showed trends for QUS parameters (P = 0.02-0.07). No association with BMP2 SNPs was observed in either cohort for either BMD or fracture. While further, more extensive genotyping across the gene is recommended, as we may not have captured all information, our preliminary data suggest that variation in BMP2 may play a previously unidentified role in aspects of bone quality, which may be age- and site-dependent.

In this longitudinal, prospective, and population-based study (n = 1044), seven BTMs were assessed before and after trauma in 113 elderly women (85 with fractures). Markers were not altered in the immediate postfracture period but were clearly elevated during fracture repair. Recent fracture should thus be taken into account when markers are used in clinical practice.Fracture may influence the levels of bone turnover markers (BTM) and have implications for their use in clinical practice. In this longitudinal, prospective, and population-based study, we assessed prefracture levels of BTMs and compared them with postfracture levels of the same individuals immediately after fracture and during fracture repair. This is the first study in which the effect of fracture on bone markers has been evaluated with prefracture samples available.Serum and urine were collected at the emergency unit from 85 women (77.9 +/- 1.8 yr) who sustained a fracture after low-energy trauma and 28 controls (77.8 +/- 2.0 yr) with similar trauma but no fracture. All were participants of the Malmö OPRA study (n = 1044), and pretrauma samples were collected 1.05 +/- 0.85 yr before. Bone turnover was assessed by seven different BTMs reflecting different stages of bone metabolism {C-terminal cross-linked telopeptides of type I collagen [S-CTX], S-TRACP5b, N-terminal propeptides of type I collagen [S-PINP], serum osteocalcin (S-OC[1-49] and S-TotalOC), urinary deoxypyridinoline [U-DPD], and urinary osteocalcin [U-OC]}.BTMs sampled within a few hours after fracture were not altered from preinjury levels. Both bone formation and bone resorption markers were, however, significantly increased 4 mo after fracture. The elevation was most pronounced after hip fracture. Bone turnover remained elevated up to 12 mo after fracture.We believe this study extends our knowledge on the skeletal postfracture metabolic processes. In addition, it may provide a basis for future means to monitor pharmacological intervention promoting fracture healing.

It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was therefore to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men.Cross-sectional case-control study.Men from infertile couples (n = 192); 18-50 years; sperm concentration20 × 10(6) /ml and population-based age-matched controls (n = 199).Blood sampling, anthropometrics, blood pressure, ankle-brachial index and assessment by dual-energy X-ray absorptiometry were undertaken. Odds ratios of biochemical hypogonadism (total testosterone8·0 nmol/l and/or luteinizing hormone ≥8·6 IU/l and/or ongoing androgen replacement therapy) were calculated. Serum concentrations of sex hormones, lipids, glucose, insulin and HbA1c were assessed and bone mineral density (BMD) evaluated.Compared to controls, the risk of hypogonadism was increased among subfertile men (OR 10; 95% CI, 5·1, 22), being highest in those with nonobstructive azoospermia. Hypogonadal men had higher HbA1c concentration (mean diff. 2·8 mmol/mol; 95% CI, 0·64, 4·9; P = 0·011) and lower lumbar spine BMD (mean diff. 0·05 g/cm(2) ; 95% CI, 0·01, 0·10; P = 0·032) compared to eugonadal subfertile men, even more pronounced in subfertile men with subnormal testosterone levels.Young subfertile men have 10 times increased OR of hypogonadism, which is linked to increased HbA1c and decreased bone mineralization. Endocrine assessment and, if needed, measures to prevent metabolic sequelae and osteoporosis should be included in the routine management of men from infertile couples.

Men and women with hip fracture have higher short-term mortality. This study investigated mortality risk over two decades post-fracture; excess mortality remained high in women up to 10 years and in men up to 20 years. Cardiovascular disease (CVD) and pneumonia were leading causes of death with a long-term doubling of risk.Hip fractures are associated with increased mortality, particularly short term. In this study with a two-decade follow-up, we examined mortality and cause of death compared to the background population.We followed 1013 hip fracture patients and 2026 matched community controls for 22 years. Mortality, excess mortality, and cause of death were analyzed and stratified for age and sex. Hazard ratio (HR) was estimated by Cox regression. A competing risk model was fitted to estimate HR for common causes of death (CVD, cancer, pneumonia) in the short and long term (1 year).For both sexes and at all ages, mortality was higher in hip fracture patients across the observation period with men losing most life years (p 0.001). Mortality risk was higher for up to 15 years (women (risk ratio (RR) 1.9 [95 % confidence interval (CI) 1.7-2.1]); men (RR 2.8 [2.2-3.5])) and until end of follow-up ((RR 1.8 [1.6-2.0]); (RR 2.7 [2.1-3.3])). Excess mortality by time intervals, censored for the first year, was evident in women (80 years, up to 10 years;80 years, for 5 years) and in men80 years throughout. CVD and pneumonia were predominant causes of death in men and women with an associated higher risk in all age groups. Pneumonia caused excess mortality in men over the entire observation period.In a remaining lifetime perspective, all-cause and excess mortality after hip fracture was higher even over two decades of follow-up. CVD and pneumonia reduce life expectancy for the remaining lifetime and highlights the need to further improve post-fracture management.

The objective of this study was to review and describe the current state of Swedish osteoporosis care and to highlight ongoing challenges. This report encompasses quantitative health outcomes based on Swedish registry data as well as organizational and management aspects. Swedish osteoporosis care is characterized by a significant burden of disease, difficulties in identifying high-risk patients, and fragmented pathways for patients in need of secondary fracture prevention. This report aimed to describe the current state, gaps, and challenges in Swedish osteoporosis care, using Swedish national databases, questionnaires, and interviews with healthcare representatives. A secondary aim was to develop quality and process measures to compare differences between counties and to use those measures to describe the interaction between quantitative health outcomes and aspects of care organization and management. In conjunction with fractures, a considerably smaller proportion of men are treated than women, and a smaller proportion of older women are treated compared to younger groups. Between 3 and 16 % of patients receive treatment after a fracture, and the treatment rate in this patient group can likely increase. In addition to an unsatisfactory treatment rate, a limited number of those treated continue treatment throughout the recommended treatment durations, leading to increased risk of fracture. With a substantial variation between counties, there is a clear difficulty to identify non-persistent patients and switch to an alternative treatment. Collaboration around the patient across specialties has been lacking, and systems for secondary prevention have been concentrated to a few counties. However, when this study was conducted, there was a general trend towards implementing regional care programs. This report suggests possible strategies for improving quality of care and, hopefully, it can provide a basis for future evaluations and regional improvement of osteoporosis care in Sweden and other countries.

The aim of every patient with hip fracture is to regain previous function but we know little about the outcome, especially patient-reported outcome. We wanted to investigate what factors influence the result one year after hip fracture, including fast-track for hip fracture patients, as well as investigating the patients' satisfaction with their rehabilitation and to what degree they regained their pre-fracture function.All patients (20 years, non-pathological fracture, residents in the catchment area, n=664) having surgery for hip fracture at our hospital during 2011 were included in a retrospective cohort study. From medical records, information was gathered about pre-fracture condition as well as fracture type, surgical details, length of stay and whether the patient entered the hospital through the fast-track system. Medical records were scrutinised for general complications up to six months and for local complications up to one year after surgery. A postal questionnaire was sent one year after surgery inquiring about health status, pain and satisfaction along with multiple-choice questions regarding mobility and rehabilitation. Variables were analysed with linear regression or the proportional odds model.The most common general complications were new falls, pneumonia and new fractures. Deep infection was the most frequent local complication. The only significant effect of the fast-track system was shorter time to surgery (78 vs. 62% had surgery within 24h, p0.001). A total of 29% reported to have regained their previous mobility and 30% considered the rehabilitation to be adequate. Mean value for pain VAS was 24 (SD 22) and for satisfaction 28 (SD 25). Absence of general and local complications correlated to satisfaction and hip pain. General complications correlated to loss of function. Higher age correlated to inadequate rehabilitation.General complications seem to be the major risk factor, being the only factor affecting functional outcome and together with local complications affecting pain and satisfaction. To avoid general complications, co-operation between orthopaedic surgeons and internists may be crucial in the aftercare of hip fracture patients. A majority did not receive adequate rehabilitation and efforts need to be made to improve the rehabilitation process.

BACKGROUND CONTEXT: Idiopathic scoliosis is a spinal deformity affecting approximately 3% of otherwise healthy children or adolescents. The etiology is still largely unknown but has an important genetic component. Genome-wide association studies have identified a number of common genetic variants that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding.PURPOSE: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants.STUDY DESIGN: This was a case control study.PATIENT SAMPLE: A total of 1,739 patients with idiopathic scoliosis and 1,812 controls were included.OUTCOME MEASURE: The outcome measure was idiopathic scoliosis.METHODS: The variants rs10510181, rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5'UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing, were Sanger sequenced in the 100 pooled samples.RESULTS: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10(-18)). We identified 20 novel variants by exome sequencing after filtration and an initial genotyping validation. However, we could not verify any association to idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. We did not find any variants in the 5'UTR, noncoding exon and promoter regions of LBX1.CONCLUSIONS: Here, we confirm LBX1 as a susceptibility gene for idiopathic scoliosis in a Scandinavian population and report that we are unable to find evidence of other genes of similar or stronger effect.

This study examines the impact of smoking and smoking cessation on fracture risk in 75-year-old women followed for 10 years. Smoking increased fracture risk, especially for vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other fracture types. The purpose of this study was to examine effects of smoking and smoking cessation on fracture risk. This prospective observational population-based study followed 1033 women during 10 years from age 75. Data regarding smoking were collected at age 75. Hazard ratios (HRs) and 95 % confidence intervals for fracture were calculated using competing risks proportional hazards regression. Both former smokers and current smokers had an increased risk for any fracture (HR 1.30; 1.03–1.66, and HR 1.32; 1.01–1.73, respectively) and any osteoporotic fracture (hip, proximal humerus, distal radius, vertebra) (HR 1.31; 1.01–1.70 and HR 1.49; 1.11–1.98, respectively) compared to non-smokers. Former smokers had an increased risk for proximal humerus fractures (HR 2.23; 1.35–3.70), and current smokers had an increased risk for vertebral fractures (HR 2.30; 1.57–3.38) compared to non-smokers. After adjustment for weight, previous fractures, alcohol habits, bone mineral density (BMD), use of corticoids, vitamin D, bisphosphonates, and previous falls, former smokers had an increased risk for proximal humerus fracture (HR 2.07; 1.19–3.57) and current smokers had an increased risk for osteoporotic (HR 1.47; 1.05–2.05) and vertebral fractures (HR 2.50; 1.58–3.95) compared to non-smokers. Former smokers had a decreased risk for vertebral fractures, but not for other types of fractures, compared to current smokers. Smoking increased the risk for fracture among elderly women, especially vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other types of fractures.

Summary: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. Introduction: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation’s Capture the Fracture® programme developed a Best Practice Framework ( BPF ) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. Methods: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black ( insufficient ) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service ( FLS ) map. Results: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. Conclusion: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.

ALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women.Three SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n=1061 women; all 25y) and OPRA (n=1044 women; all 75y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA.In the elderly women ALOX15 (rs2619112) was associated with CRP levels (p=0.004) and incident fracture of any type (p=0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p=0.002-0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p=0.034; hip p=0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort.This study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.

Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.Recently, the association between high serum homocysteine (Hcy) levels and an increased risk of fracture has been described.Hcy levels were measured at baseline in 996 women, all 75 years old. Vitamin B(12), folate, serum cross-linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin, urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound (QUS), and physical performance were assessed at baseline. Fractures and mortality were recorded during a mean follow-up of 7.0 years.Bone marker levels were higher in women with Hcy in the highest quartile compared with all other women (p0.05). The most evident correlation between Hcy and a bone marker was seen with CTX (r = 0.19, p0.001). aBMD (hip) was 4% lower, QUS was up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest quartile compared with the other women (p0.05). During the follow-up, 267 women sustained at least one low-energy fracture (including 69 hip fractures). When women in the highest Hcy quartile were compared with all other women, the hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89-1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for confounders did not substantially change these associations. Adjustment for PTH increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B(12) or folate was not associated with increased fracture risk or mortality.High Hcy levels were associated with higher bone turnover, poor physical performance, and lower BMD. There was no clear association to fracture risk. The increased mortality among women with high Hcy levels indicates that a high Hcy level may be a marker of frailty.

In a large cohort of elderly women followed for 10 years, we found that balance, gait speed, and self-reported history of fall independently predicted fracture. These clinical risk factors are easily evaluated and therefore advantageous in a clinical setting. They would improve fracture risk assessment and thereby also fracture prevention. The aim of this study was to identify additional risk factors for osteoporosis-related fracture by investigating the fracture predictive ability of physical performance tests and self-reported history of falls. In the population-based Osteoporosis Prospective Risk Assessment study (OPRA), 1044 women were recruited at the age of 75 and followed for 10 years. At inclusion, knee extension force, standing balance, gait speed, and bone mineral density (BMD) were examined. Falls the year before investigation was assessed by questionnaire. Cox proportional hazards regression analysis was used to determine fracture hazard ratios (HR) with BMD, history of fracture, BMI, smoking habits, bisphosphonate, vitamin D, glucocorticoid, and alcohol use as covariates. Continuous variables were standardized and HR shown for each standard deviation change. Of all women, 427 (41 %) sustained at least one fracture during the 10-year follow-up. Failing the balance test had an HR of 1.98 (1.18–3.32) for hip fracture. Each standard deviation decrease in gait speed was associated with an HR of 1.37 (1.14–1.64) for hip fracture. Previous fall had an HR of 1.30 (1.03–1.65) for any fracture; 1.39 (1.08–1.79) for any osteoporosis-related fracture; and 1.60 (1.03–2.48) for distal forearm fracture. Knee extension force did not show fracture predictability. The balance test, gait speed test, and self-reported history of fall all hold independent fracture predictability. Consideration of these clinical risk factors for fracture would improve the fracture risk assessment and subsequently also fracture prevention.

Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed ( r =0.17, P

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.

Objective: To develop core recommendations for the learning outcomes of an undergraduate curriculum in musculoskeletal conditions for any parts of the globe. Methods: Recommendations were developed by wide consultation with experts in orthopaedics, rheumatology, osteoporosis, and rehabilitation from all parts of the world who had interest and experience in these specialties, with the support of international and national societies. All possible knowledge, skills, and attitudes that might be of relevance to musculoskeletal conditions were initially considered and then reduced to those considered essential for all doctors. Results: The recommendations focus on (a) basic skills to assess and diagnose musculoskeletal problems; (b) the competency to assess specific common or urgent musculoskeletal problems; (c) the theoretical background of the conditions and their management; and (d) the core knowledge necessary to support diagnosis and management, including basic sciences. At the end of the course, all students should be able to differentiate normal from abnormal locomotor symptoms in a patient, determine the relevant investigations and interpret the results, formulate a limited differential diagnosis, recognise the impact of the problem on the individual patient, and make an appropriate management plan. Conclusions: The recommendations set global standards for the minimum level of competence in managing patients with musculoskeletal problems. They define what all doctors should know when graduating from medical school, regardless of further specialisation. They are intended to form the basis of a curriculum for a musculoskeletal course and can be adapted for any medical school in any country throughout the world.

Background: The chronological age is clearly the strongest risk factor for fractures or death. Age as a concept can be described exactly as chronological age. Age in relative terms can be described as biological age. Objective: We postulated that, even without taking into account known or unknown comorbidity, an immediate and totally subjective evaluation of an individual’s biological age is predictive of forthcoming fractures and death. Methods: At baseline the biological age was estimated in 1,004 randomly recruited ambulatory 75-year-old women. All women were of the same ethnic background. Two independent observers estimated the biological age within 15 s of first sight of each woman. Based on this estimation of the biological age, the women were divided into tertiles. The women were then followed prospectively for a mean of 4.6 (range 3.0–6.5) years. All retrospective fractures and prospective fractures and deaths were registered. Results: When the tertile of the biologically oldest women was compared with all other women, their odds ratio for sustaining any type of prospective fracture was 1.71 (95% confidence interval 1.22–2.39), for hip fractures 2.69 (1.42–5.11), for clinical vertebral fractures 2.83 (1.57–5.11), and for multiple fractures 3.17 (1.64–6.10). Also, when retrospectively sustained fractures were included, the predictive ability for biological age remained. The death rate amongst the tertile of biologically oldest women was increased when compared with the rest of the women (odds ratio 4.33, CI 3.62–5.17). Conclusions: In ambulatory elderly women, without specific consideration of comorbidity, a subjective estimate of the biological age is predictive of future fractures and death. Subjective estimation of the biological age, in relation to the chronological age, is a valuable indicator of health, conveying additional information that merits its use in clinical practice.

We studied the ability of various markers of bone turnover to predict fracture in 1040 randomly recruited 75-year-old women. A total of 178 of the women sustained at least one fracture during follow-up (mean, 4.6 years). In elderly women, TRACP5b and urinary fragments of osteocalcin are promising new markers for prediction of fracture, in particular, vertebral fracture. Introduction: Biochemical markers reflecting bone turnover may improve the prediction of fractures. Materials and Methods: The ability of 10 markers of bone turnover to predict fracture in 1040 elderly women in the Malmo OPRA study was studied. Serum bone-specific alkaline phosphatase and four different forms of serum osteocalcin (S-OC) were analyzed as markers of bone formation and serum C-terminal cross-linking telopeptides of type I collagen (S-CTX), serum TRACP isoform 5b (S-TRACP5b) and urinary free deoxypyridinoline (U-DPD) as markers of bone resorption. Two novel assays for osteocalcin fragments in urine (U-OC) were analyzed. Areal BMD (aBMD) was measured by DXA in the femoral neck and lumbar spine. Results: In total, 231 fractures were sustained by 178 of the women during a 3- to 6.5-year (mean, 4.6 years) follow-up period. When women with prospective fractures were compared with women without fractures, S-TRACP5b, S-CTX, one S-OC, and one U-OC were higher in women with a fracture of any type (all p < 0.05), and all bone markers were higher in women with clinical vertebral fracture (all p < 0.05). Markers were not significantly elevated in women with hip fracture. When women within the highest quartile of a bone marker were compared with all others, S-TRACP5b and one U-OC predicted the occurrence of a fracture of any type (odds ratio [OR]), 1.55 and 1.53; p < 0.05). S-TRACP5b, the two U-OCs, and S-CTX predicted vertebral fracture (OR, 2.28, 2.75, 2.71, and 1.94, respectively; all p < 0.05), and the predictive value remained significant for S-TRACP5b and the two U-OCs after adjusting for aBMD (OR, 2.02–2.25; p < 0.05). Bone markers were not able to predict hip fracture. Conclusion: These results show that biochemical markers of bone turnover can predict fracture, and in particular, fractures that engage trabecular bone. S-TRACP5b and U-OC are promising new markers for prediction of fracture.

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.

Recently, an ultrasound (US) device for measurement of amplitude-dependent speed of sound in four proximal phalanges of the hand (DBM Sonic 1200®, IGEA, Carpi, Mo, Italy) has been introduced but has not been thoroughly investigated in populations at most risk for fragility fractures (i.e., elderly women). As part of the Malmo Osteoporosis Prospective Risk Assessment study (OPRA), we investigated 1044 randomly selected women, all 75 yr of age, with US of the phalanges and, for comparison, also with two more established methods for bone mass measurement: US of the calcaneus and dual-energy X-ray absorptiometry (DXA) of the hip and spine, both methods having an ability to predict fracture. A self-assessment questionnaire was used to obtain information on previous fracture and age at fracture event. We found a low correlation between US of the phalanges and US of the calcaneus speed of sound (SoS) ( r = 0.11, p r = 0.09, p r = 0.09, p r = 0.10, p p

Risk Of Major Osteoporotic Fracture (Hip, Vertebral, Radius, Humerus [Mof]) After First, Second And Third Fragility Fracture In A Swedish General Population Cohort

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

This study of elderly Swedish women investigated the association between chronic vitamin D insufficiency and osteoporotic fractures occurring between ages 80-90. The incidence and risk of hip and major osteoporotic fractures was significantly higher in elderly women with low vitamin D levels maintained over 5 years.Vitamin D insufficiency among the elderly is common; however, relatively little is known about the effects of long-term hypovitaminosis D on fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80 to determine if continuously low 25(OH)D levels are associated with increased 10-year fracture incidence.One thousand forty-four Swedish women from the population-based OPRA cohort, all 75 years old, attended at baseline (BL); 715 attended at 5 years. S-25(OH)D was available in 987 and 640, respectively and categorized as:50 (Low), 50-75 (Intermediate), and75 nmol/L (High). Incident fracture data was collected with maximum follow-up to 90 years of age.Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D at both baseline and 5 years (22.2 % (Low) vs. 6.6 % (High); p = 0.003). Between age 80-90, hip fracture incidence was more than double that of women in the high category (27.9 vs. 12.3 %; p = 0.006). Within 5-years, 50 % of women in the continuously low group compared to 34 % in the continuously high 25(OH)D group had an osteoporotic fracture (p = 0.004) while 10-year incidence was higher compared to the intermediate (p = 0.020) but not the high category (p = 0.053). The 10-year relative risk of hip fracture was almost three times higher and osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D category compared to the high category (HR 2.7 and 1.7; p = 0.003 and 0.023, respectively).In these elderly women, 25(OH)D insufficiency over 5-years was associated with increased 10-year risk of hip and major osteoporotic fractures.

We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.

In the elderly, degenerative changes in the lumbar spine are common, contributing to falsely elevated bone mineral density (BMD) values. The parathyroid hormone (PTH) system plays an important role in the regulation of bone turnover and we explore the hypothesis that polymorphisms (SNPs) within genes in this pathway (PTH, PTHLH, PTH1R and PTH2R) contribute to degenerative manifestations of the spine in elderly women. The study included 1,004 Swedish women aged 75 years from the population-based OPRA cohort who attended follow-up at 5 and 10 years. Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) and each individual vertebra was evaluated visually on the DXA image for apparent degenerative manifestations. Six SNPs in PTH and 3 SNPs each in PTH1R, PTH2R and PTHLH were analysed. Among women with degenerative manifestations at the lumbar spine, there was an over-representation at baseline of those carrying the PTH2R SNP rs897083 A-allele (p = 0.0021; odds ratio 1.5 95 % CI 1.2-2.0) and across the duration of follow-up (p = 0.0008). No association was observed between degenerative manifestations and variation in the other genes. None of the PTH hormone system genes were associated with vertebral fracture. Variation in the PTH2R gene (Chr2q34, rs897083) may contribute to the age-associated degenerative manifestations that develop at the lumbar spine.

Summary\ud The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world.\ud \ud Introduction\ud FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk.\ud \ud Methods\ud Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery.\ud \ud Results\ud The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities.\ud \ud Conclusion\ud Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.

The aims of this study were to provide normative data for dual-energy X-ray absorptiometry (DXA) in 25-yr-old women and evaluate whether young adult Swedish women have bone mineral density (BMD) comparable with DXA manufacturer reference values and other equivalent populations. BMD at all sites was measured in the population-based Peak-25 cohort (n = 1061 women; age, 25.5 ± 0.2yr). BMD values were standardized (sBMD) and compared against the Third National Health and Nutrition Examination Survey (NHANES III) and other cohorts. Based on the DXA manufacturer-supplied reference values, Z-scores were 0.54 ± 0.98 (femoral neck [FN]), 0.47 ± 0.96 (total hip [TH]), and 0.32 ± 1.03 (lumbar spine [LS]). In comparison with other studies, sBMD was higher in the Peak-25 cohort (FN, 1.5%-8.3%; TH, 3.9%-9.2%; and LS, 2.4%-6.5%) with the exception of trochanter-sBMD which was 2.5% lower compared with NHANES III. The concordance in identifying those in the lowest or highest quartile of BMD was highest between hip measurements (low, 71%-78% and high, 70%-84%), corresponding discordance of 0%-1%. At this age, the correlation between DXA sites was strong (r = 0.62-0.94). BMD in Swedish young adult women is generally higher than has been reported in other equivalently aged European and North American cohorts and suggests that the high fracture incidence in Sweden is not explained by lower peak bone mass. The use of nonregional-specific DXA reference data could contribute to misdiagnosed osteoporosis in elderly women.

Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women. INTRODUCTION: The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women. METHODS: One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1-L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181-3,620 g), and high (≥3,621 g) birth weight. RESULTS: Significant correlations were observed between birth weight and TB-BMC (r = 0.159, p < 0.001), FN-BMC (r = 0.096, p < 0.001), TH-BMC (r = 0.102, p = 0.001), LS-BMC (r = 0.095, p = 0.002), and lean mass (r = 0.215, p < 0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3-0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed CONCLUSIONS: Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.

Smoking is associated with postmenopausal bone loss and fracture, but the effect of smoking on bone in younger women is unclear. Peak bone mass is an important determinant for fracture risk; therefore, our aim was to evaluate the association between smoking and bone mass in 25-year-old women, specifically the influence of daily cigarette consumption and total exposure, duration, age at starting smoking, and time since smoking cessation on bone density and fracture risk. Smoking and bone mineral density (BMD) data were available for 1,054 women from the PEAK-25 cohort. Analyses comparing current smokers with women who never smoked were performed using number of cigarettes per day, pack-years, smoking duration, age smoking started, and, for former smokers, age at quitting. BMD did not differ between never, former, and current smokers; and the relative fracture risk in smokers was not significant (relative risk [RR] = 1.2, 95 % confidence interval 0.8–1.9). Among current smokers, BMD decreased with a dose response as cigarette consumption increased (femoral neck p = 0.037). BMD was not significantly lower in young women who had smoked for long duration or started smoking early (p = 0.07–0.64); long duration and early start were associated with higher body mass index (BMI; p = 0.038). Lower BMD persisted up to 24 months after smoking cessation (p = 0.027–0.050), becoming comparable to never-smokers after 24 months. Hip BMD was negatively associated with smoking and dose-dependent on cigarette consumption. Smoking duration was not associated with BMD, although young women with a long smoking history had higher BMI, which might attenuate the adverse effects from smoking.

The purpose of this study was to define the bone metabolic properties during the postfracture period in elderly women with hip fracture. Osteocalcin (Oc), a marker of bone formation, was measured in 58 women with hip fracture (77 +/- 7 years) admitted to the hospital from their own homes. Serum samples were taken on average 5 h (range 1-21) from fracture and at follow-up, on average 4.6 months later. Comparison was made with 58 age-matched (79 +/- 5 years) women. Women with hip fracture had initially 30% lower Oc levels compared to the controls (p = 0.0001). The Oc level was independent of time elapsed from trauma, within 18 h, after which the level further decreased. At follow-up, Oc showed a 44% increase (p = 0.0001) and had reached the level of the controls, but not beyond it. A concomitant, but less marked increase was noted for alkaline phosphatase (ALP) (p = 0.0001). We conclude that although the bone formation, as assessed by Oc, is apparently lower in elderly women who sustain a hip fracture, the ability to induce a fracture response, with an increased bone turnover during fracture healing is intact. Subsequently, it is essential that a time perspective is applied, as the bone metabolic changes in patients having sustained a fracture are related to the time elapsed from fracture.

Migration of 65 Charnley stems implanted with modern cementing techniques was studied by roentgen stereophotogrammetry. There were 25 patients with rheumatoid arthritis (RA) and 40 with osteoarthritis (OA) followed up for two years. In 43 cases a bone sample for histomorphometric analysis was obtained from the femur during the operation. In 22 cases the mean subsidence of the prosthetic head was 0.40 mm and in 20 the mean posterior migration was 1.25 mm. There was no difference in migration between the two diagnostic groups (p = 0.8) after adjusting for variations in gender, age and weight. Male gender was associated with increased subsidence (p = 0.006). Histological examination showed that the RA series had more osteoid surface (p = 0.04), but neither this, nor any of the other histomorphometric variables, influenced migration. These results suggest that, unlike the acetabular socket, the cemented Charnley femoral component is equally secure in osteoarthritis and in rheumatoid arthritis, and that its initial fixation is not influenced by the quality of the local cancellous bone. Our results provide data with which the early performance of new prosthetic designs and fixation methods can be compared.

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.

Osteoclast activity and the fine balance between bone formation and resorption is affected by inflammatory factors such as cytokines and T lymphocyte activity, mediated by major histocompatibility complex (MHC) molecules, in turn regulated by the MHC class II transactivator (MHC2TA). We investigated the effect of functional polymorphisms in the MHC2TA gene (CIITA), and two additional genes; C-type lectin domain 16A (CLEC16A), in linkage disequilibrium with CIITA and Interferon-γ (IFNG), an inducer of CIITA; on bone density, bone resorption markers, bone loss and fracture risk in 75 year-old women followed for up to 10 years (OPRA n = 1003) and in young adult women (PEAK-25 n = 999). CIITA was associated with BMD at age 75 (lumbar spine p = 0.011; femoral neck (FN) p = 0.049) and age 80 (total body p = 0.015; total hip p = 0.042; FN p = 0.028). Carriers of the CIITA rs3087456(G) allele had 1.8-3.4% higher BMD and displayed increased rate of bone loss between age 75 and 80 (FN p = 0.013; total hip p = 0.030; total body p = 3.8E(-5)). Despite increasing bone loss, the rs3087456(G) allele was protective against incident fracture overall (p = 0.002), osteoporotic fracture and hip fracture. Carriers of CLEC16A and IFNG variant alleles had lower BMD (p

To evaluate the accuracy of bone mineral composition determination by electron microprobe analysis (EDX) the measurements have been compared to instrumental neutron activation analysis (INAA) and chemical analysis (ICPES). Bone specimens from five femoral heads were used. The trabecular content of calcium (Ca) and phosphorus (P) was analyzed by the three different methods. The EDX method allows for a microstructural analysis of intact, methylmetacrylate-embedded, undecalcified bone and the measuring points can thus be distinctly identified centrally in each trabecula. The analysis yielded 25.8 +/- 0.7 wt % Ca and 10.5 +/- 0.1 wt % P, compared with 22.2 +/- 0.5 and 23.0 +/- 1.0 wt % Ca, and 9.83 +/- 0.21 and 10.02 +/- 0.44 wt % P for INAA and ICPES, respectively. The EDX analysis was calibrated by consecutive measurements of a hard, pressed tablet of hydroxyapatit of known content. The mean Ca content deviated with -0.38 wt % from the given content and P with -0.89 wt %. We could not verify any particular interference from the embedding procedure, however, it is possible that the relatively lower P content still may reflect this. The magnesium (Mg) concentration was 0.31 +/- 0.02 wt % by EDX and 0.26 +/- 0.02 wt % by INAA. The EDX analytical method provides a useful tool for simultaneous elemental quantification in bone. It has the advantage of permitting the use of regular bone biopsy material and thus allowing for a unique microstructural evaluation of the degree of mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/β-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In two cohorts of Swedish women: OPRA (n=1002; age 75 years) and PEAK-25 (n=1005; age 25 years), eleven single nucleotide polymorphisms (SNPs) from Wnt pathway genes (LRP4; LRP5; G protein-coupled receptor 177, GPR177) were analyzed for association with Bone Mineral Density (BMD), rate of bone loss, hip geometry, quantitative ultrasound and fracture. Additionally, interaction of LRP4 with LRP5, GPR177 and BMP2 were analyzed. LRP4 (rs6485702) was associated with higher total body (TB) and lumbar spine (LS) BMD in the PEAK-25 cohort (p=0.006 and 0.005 respectively), and interaction was observed with LRP5 (p=0.007) and BMP2 (p=0.004) for TB BMD. LRP4 also showed significant interaction with LRP5 for femoral neck (FN) and LS BMD in this cohort. In the OPRA cohort, LRP4 polymorphisms were associated with significantly lower fracture incidence overall (p=0.008-0.001) and fewer hip fractures (rs3816614, p=0.006). Significant interaction in the OPRA cohort was observed for LRP4 with BMP2 and GPR177 for FN BMD as well as for rate of bone loss at TB and FN (p=0.007-0.0001). In conclusion, LRP4 and interaction between LRP4 and genes in the Wnt and BMP signaling pathways modulate bone phenotypes including peak bone mass and fracture, the clinical endpoint of osteoporosis.

UNLABELLED: This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. INTRODUCTION: A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. METHODS: A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. RESULTS: Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these 'atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. CONCLUSIONS: Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fractures.