Socioeconomic status and risk of osteoporotic fractures and the use of DXA scans: data from the Danish population-based ROSE study.

There is a need of studies exploring the link between socioeconomic status and DXA scans and osteoporotic fracture, which was the aim of the present study. No differences in socioeconomic status and risk of osteoporotic fractures were found. However, women with further/higher education and higher income are more often DXA-scanned. INTRODUCTION: Lower socioeconomic status is known to be associated with a range of chronic conditions and with access to health care services. The link between socioeconomic status and the use of DXA scans and osteoporotic fracture, however, needs to be explored more closely. Therefore, the aim of this study was to examine the relationship between socioeconomic status and both DXA scan utilization and major osteoporotic fractures (MOF) using a population-based cohort of Danish women and national registers. METHODS: The study included 17,155 women (65-81 years) sampled from the Risk-stratified Osteoporosis Strategy Evaluation study (ROSE). Information on socioeconomic background, DXA scans, and MOFs was retrieved from national registers. Competing-risk regression analyses were performed. Mean follow-up was 4.8 years. RESULTS: A total of 4245 women had a DXA scan (24.7%) and 1719 (10.0%) had an incident MOF during follow-up. Analyses showed that women with basic education had a lower probability of undergoing DXA scans than women with further or higher education (greater than upper secondary education and vocational training education) (subhazard ratio (SHR) = 0.82; 95% CI 0.75-0.89, adjusted for age and comorbidity). Moreover, women with disposable income in the low and medium tertiles had a lower probability of undergoing DXA scans than women in the high-income tertile (SHR = 0.90; 95% CI 0.84-0.97 and SHR = 0.88, 95% CI 0.82-0.95, respectively, adjusted for age and comorbidity). No association between socioeconomic background and probability of DXA was found in adjusted analyses. CONCLUSION: The study found no differences in risk of osteoporotic fractures depending on socioeconomic status. However, women with further or higher education as well as higher income are more often DXA-scanned.

Use of antiosteoporotic medication in the Danish ROSE population-based screening study.

Use of antiosteoporotic medication in the population-based, risk-stratified osteoporosis strategy evaluation (ROSE) screening study, comparing the use of FRAX followed by DXA with usual care, was examined. Screening increased the overall use of medication. Being recommended treatment by the hospital and higher age increased the likelihood of starting medication, but, nevertheless, a large percentage opted not to start treatment. INTRODUCTION: The aim of the study was to examine the impact on medication prescription, adherence, and persistence of osteoporotic medicine in the randomized population-based ROSE screening study for osteoporosis. METHODS: The Danish ROSE study included a population-based random sample of women aged 65-81 years randomized to either a two-step screening program consisting of FRAX followed by DXA for high-risk participants or opportunistic screening for osteoporosis (usual care). This sub-study on the intention-to-treat population examined the impact of the screening program on antiosteoporotic medication redemption rates, adherence, and persistence using Danish registers. RESULTS: A total of 30,719 of 34,229 women were treatment-naïve. Significantly more participants in the screening group started on antiosteoporotic medication, but no differences in adherence and persistence rates were found. Higher age was associated with a higher likelihood of starting medication. A low Charlson comorbidity score (= 1) was associated with higher treatment initiation but lower adherence and persistence of antiosteoporotic treatment. A total of 31.7% of participants advised to initiate treatment did not follow the advice. CONCLUSIONS: Screening for osteoporosis using FRAX followed by DXA increased the overall use of antiosteoporotic medication in the screening group without differences in adherence and persistence rates. A large percentage of participants advised to initiate treatment did nevertheless fail to do so.

Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study.

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION: The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. METHODS: Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed. RESULTS: A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65-80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). CONCLUSIONS: Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

Osteogenesis imperfecta and the teeth, eyes, and ears-a study of non-skeletal phenotypes in adults.

Osteogenesis imperfecta (OI) is a disease causing bone fragility; however, it potentially affects all organs with a high content of collagen, including ears, teeth, and eyes. The study is cross-sectional and compares non-skeletal characteristics in adults with OI that clinicians should be aware of when caring for patients with OI. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. The skeletal fragility is pronounced; however, OI leads to a number of extra-skeletal symptoms related to the ubiquity of collagen type 1 throughout the human body. The vast majority of knowledge is derived from studies performed in the pediatric population. Thus, we aimed to investigate the nature and prevalence of ophthalmologic, odontologic, and otologic phenotypes in an adult population with OI. METHODS: The study population comprises 85 Danish OI patients (age 44.9 ± 15.9 years). Fifty-eight patients had OI type I, 12 OI type III, and 15 OI type IV according to the classification by Sillence. Audiometric evaluations and dental examinations were performed in 62 and 73 patients, respectively. Ophthalmologic investigations were performed in 64 patients, including measurements of the central corneal thickness. RESULTS: All patients, except two, had corneal thickness below the normal reference value. Patients with OI type I and patients with a quantitative collagen defect had thinner corneas compared to patients with OI type III and other patients with a qualitative collagen defect. One patient in this cohort was diagnosed with and treated for acute glaucoma. Dentinogenesis imperfecta was diagnosed in one fourth of the patients, based on clinical and radiographic findings. This condition was predominately seen in patients with moderate to severe OI. Hearing loss requiring treatment was found in 15 of 62 patients, of whom three were untreated. The most prevalent type of hearing loss (HL) was sensorineural hearing loss, whereas conductive HL was solely seen in patients with OI type III. The patients with the most severe degrees of HL were patients with mild forms of OI. Age was associated with increased HL. CONCLUSION: Although significant health problems outside the skeleton are frequent in adult patients with OI, the patients are not consistently monitored and treated for their symptoms. Clinicians treating adult patients with OI should be aware of non-skeletal health issues and consider including regular interdisciplinary check-ups in the management plan for adult OI patients.

Non-participation in systematic screening for osteoporosis-the ROSE trial.

Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65-81 years. Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis. INTRODUCTION: Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis. METHODS: Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers. RESULTS: A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking "not interested in DXA" in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment. CONCLUSIONS: Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.

Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure.

Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. INTRODUCTION: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. METHODS: The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I (n = 58), III (n = 12), and IV (n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset (n = 67). RESULTS: A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect (p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD (p < 0.005), thinner cortexes (p < 0.001), and reduced trabecular number (p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA. CONCLUSION: The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities.

Non-intercepted dose errors in prescribing anti-neoplastic treatment: a prospective, comparative cohort study.

BACKGROUND: The incidence of non-intercepted prescription errors and the risk factors involved, including the impact of computerised order entry (CPOE) systems on such errors, are unknown. Our objective was to determine the incidence, type, severity, and related risk factors of non-intercepted prescription dose errors. PATIENTS AND METHODS: A prospective, comparative cohort study in two clinical oncology units. One institution used a CPOE system with no connection to the electronic patient record system, while the other used paper-based prescription forms. All standard prescriptions were included and reviewed. Doses were recalculated according to the guidelines of each institution, using the patient data as documented in the patient record, the paper-based prescription form, or the CPOE system. A non-intercepted prescription dose error was defined as ≥10% difference between the administered and the recalculated dose. RESULTS: Data were collected from 1 November 2012 to 15 January 2013. A total of 5767 prescriptions were evaluated, 2677 from the institution using CPOE and 3090 from the institution with paper-based prescription. Crude analysis showed an overall risk of a prescription dose error of 1.73 per 100 prescriptions. CPOE resulted in 1.60 and paper-based prescription forms in 1.84 errors per 100 prescriptions, i.e. odds ratio (OR) = 0.87 [95% confidence interval (CI) 0.59-1.29, P = 0.49]. Fifteen different types of errors and four potential risk factors were identified. None of the dose errors resulted in the death of the patient. CONCLUSIONS: Non-intercepted prescribing dose errors occurred in <2% of the prescriptions. The parallel CPOE system did not significantly reduce the overall risk of dose errors, and although it reduced the risk of calculation errors, it introduced other errors. Strategies to prevent future prescription errors could usefully focus on integrated computerised systems that can aid dose calculations and reduce transcription errors between databases.

Peak muscle mass in young men and sarcopenia in the ageing male.

SUMMARY: The prevalence of sarcopenia increases with age. The diagnosis of sarcopenia relies in part on normative data on muscle mass, but these data are lacking. This study provides population-based reference data on muscle mass in young men, and these results may be used clinically for the diagnosis of sarcopenia in men. INTRODUCTION: The ageing population increases the prevalence of sarcopenia. Estimation of normative data on muscle mass in young men during the peak of anabolic hormones is necessary for the diagnosis of sarcopenia in ageing males. The purposes of this study were to provide population-based reference data on lean body mass (LBM) in young men during the time of peak levels of GH/IGF-1 and testosterone and further to apply the reference data on a population-based sample of men aged 60-74 years to estimate the prevalence of sarcopenia. METHODS: This is a cross-sectional, population-based single-centre study. Our participants are from random selection of 783 men, aged 20-29 years, and 600 men, aged 60-74 years. LBM was assessed by dual-energy X-ray absorptiometry (DXA). LBM T-scores were calculated on the basis of LBM in the young participants. Muscle function in the lower extremities was measured using a leg extension power (LEP) rig in the ageing participants. RESULTS: Total lean body mass (TLB) was (mean (SD)) 64.7 kg (6.8) in the young and 60.4 kg (6.4) in the ageing men (p<0.001). Lower extremity lean mass (LELB) was 22.0 kg (2.6) in the young and 19.2 kg (2.4) in the ageing men (p<0.001). In the ageing men, TLB and LELB T-scores were -0.64 (0.94) and -1.09 (0.94). A total of 4.8 and 8.5% had a TLB or LELB T-score of less than -2 and a LEP in the lowest quartile. CONCLUSIONS: This study provides population-based reference data on LBM in men, and these data may be used clinically for the diagnosis of sarcopenia.

Subsequent fracture rates in a nationwide population-based cohort study with a 10-year perspective.

SUMMARY: Fractures after the age of 50 are frequently observed in Denmark, and many of these may be osteoporotic. This study examined the incidence of all and subsequent fractures in a 10-year period from 2001 to 2011. The incidence of subsequent fractures was high, especially following hip fracture. INTRODUCTION: The purpose of this study is to examine patterns of subsequent fractures and mortality rates over a 10-year period in patients already suffering from fracture. METHODS: The study was designed as a nationwide, register-based follow-up study. Patients were included if diagnosed with an index fracture (ICD-10 codes: S22.x, S32.x, S42.x, S52.x, S62.x, S72.x, S82.x, S92.x, T02.x, T08.x, T10.x and T12.x) between January 1st, 2001 and December 31st, 2001 and if older than 50 years at time of fracture. The patients were investigated for future subsequent fractures from January 1st, 2002 to December 31st, 2011. RESULTS: In this study, we demonstrated that patients with fractures (especially hip fractures) have a high risk of subsequent fractures, especially hip fracture. Other fractures, which are not commonly considered as osteoporotic fractures, such as lower leg, were frequently observed in the 10 years following index fracture. The cumulative incidence proportion (CIP) of subsequent fractures during the 10-year follow-up period was high for all recurrent fractures (9-46 %). Subsequent hip fracture, regardless of index fracture, had the highest CIP across the study period, ranging from 9 to 40 %. Appendicular fractures were often followed by a recurrent fracture, or subsequent fractures at a more proximal location in the same limb, i.e. forearm fractures were followed by humerus fractures. These results have not been previously demonstrated to this extent, and according to our knowledge, no previous studies have estimated cumulative 10-year subsequent fracture incidences for any non-hip fractures. CONCLUSION: Patients suffering a fracture (and especially a hip fracture) have a high incidence of subsequent fracture. Fractures after the age of 50 may be considered an early warning of increased risk for future fractures in many patients.

Similar reference intervals for total testosterone in healthy young and elderly men: results from the Odense Androgen Study.

CONTEXT: Ageing in men is associated with changes in levels of sex hormones. OBJECTIVE: To evaluate differences in sex hormones in young and elderly men and the significance of comorbidity and fat mass on sex hormones in elderly men. DESIGN: Cross-sectional. PATIENTS: Seven hundred and eighty-three men aged 20-29 years and 600 men aged 60-74 years randomly recruited from the background population. MEASUREMENTS: Sex hormones and sex hormone-binding globulin (SHBG) were measured, and reference intervals were determined in healthy individuals in both groups and in elderly men stratified according to whether they were obese or lean (waist circumference ≥102 cm). RESULTS: Sex hormones were lower and SHBG higher in elderly men compared with the young cohort. Lower cut-offs for total testosterone (TT) in healthy, young and elderly men were similar [Lower cut-off (95% CI): Young: 11·7 (11·2-12·1) vs elderly: 11·2 (10·3-12·1) nmol/l], but lower and higher cut-offs of bioavailable testosterone (BT) and free testosterone (FT) were higher in young men. Higher levels of androgens were found in healthy elderly men compared with those with a chronic disease or obesity. Androgens were inversely associated with central fat mass (CFM), whereas SHBG was inversely and directly associated with CFM and lower extremity fat mass, respectively, in both young and elderly men. CONCLUSION: Reference intervals for TT were comparable in healthy young and elderly men, but reference intervals for FT and BT were lower in elderly men due to higher levels of SHBG. Androgens and SHBG were lower in elderly men with chronic disease and inversely associated with CFM.

High bone mineral apparent density in children with X-linked hypophosphatemia.

UNLABELLED: Bone mineral apparent density (BMAD) in children with X-linked hypophosphatemia (XLH) was evaluated, as they are unlikely to have extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. Children with XLH also had significantly higher BMAD of the spine compared to femoral neck. INTRODUCTION: BMAD obtained by dual-energy X-ray absorptiometry scans in children with XLH was evaluated, as they are unlikely to have the extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. METHODS: A total of 15 children with biochemically and genetically verified XLH were recruited. Anthropometric measurements were performed, and to correct for the short stature (small bones), the BMAD of the spine and the femoral neck was evaluated. RESULTS: Z-scores of BMAD of the spine (mean (95 % CI); 2.0 (1.3-2.7); p < 0.001) were significantly elevated compared to reference children. Z-scores of the femoral neck (1.0 (-0.0 to 2.1); p = 0.059) tended to be elevated. Spine Z-scores were significantly higher than the Z-scores of the femoral neck, (paired t test, p = 0.02). BMAD of the spine was evaluated according to the Molgaard's approach; XLH children had normal bone size of the spine for age due to a normal sitting height Z-score of -0.4 (-1.0 to 0.1); p = 0.1. Z-scores of bone mineral content (BMC) of the spine for bone area were elevated (1.4 (0.8-2.1); p < 0.001). No reference data were available to allow evaluation of the BMAD of the femoral neck by the Molgaard's approach. CONCLUSIONS: Children with XLH have an increased BMAD and a high BMC for bone area at the lumbar spine, and this was due to causes other than extra-skeletal ossifications and corrected for bone size. The BMAD of the spine was significantly higher compared to the femoral neck.

Polymorphisms of muscle genes are associated with bone mass and incident osteoporotic fractures in Caucasians.

The interaction between muscle and bone is complex. The aim of this study was to investigate if variations in the muscle genes myostatin (MSTN), its receptor (ACVR2B), myogenin (MYOG), and myoD1 (MYOD1) were associated with fracture risk, bone mineral density (BMD), bone mineral content (BMC), and lean body mass. We analyzed two independent cohorts: the Danish Osteoporosis Prevention Study (DOPS), comprising 2,016 perimenopausal women treated with hormone therapy or not and followed for 10 years, and the Odense Androgen Study (OAS), a cross-sectional, population-based study on 783 men aged 20-29 years. Nine tag SNPs in the four genes were investigated. In the DOPS, individuals homozygous for the variant allele of the MSTN SNP rs7570532 had an increased risk of any osteoporotic fracture, with an HR of 1.82 (95 % CI 1.15-2.90, p = 0.01), and of nonvertebral osteoporotic fracture, with an HR of 2.02 (95 % CI 1.20-3.41, p = 0.01). The same allele was associated with increased bone loss (BMC) at the total hip of 4.1 versus 0.5 % in individuals either heterozygous or homozygous for the common allele (p = 0.006), a reduced 10-year growth in bone area at the total hip of 0.4 versus 2.2 and 2.3 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.01), and a nonsignificantly increased 10-year loss of total-hip BMD of 4.4 versus 2.7 and 2.9 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.08). This study is the first to demonstrate an association between a variant in MSTN and fracture risk and bone loss. Further studies are needed to confirm the findings.

Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat.

The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study of 6 months testosterone therapy (gel) in 38 men aged 60-78 years with bioavailable testosterone <7.3 nmol/l and waist circumference >94 cm was performed. Clinical evaluation, OPG, and C-reactive protein (CRP) measurements were carried out. Lean body mass (LBM), total fat mass, and bone mineral density (BMD) were established by dual X-ray absorptiometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by magnetic resonance imaging. Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM (Δ LBM positive), n=14. Data are presented as median (interquartile range). Testosterone therapy decreased total fat mass and SAT, whereas VAT was unchanged (n=38). OPG levels decreased during testosterone therapy (from 2.0 (1.9-2.5) to 1.9 (1.6-2.2) ng/ml, p<0.05 vs. placebo), whereas CRP levels were unchanged (n=38). In responders to testosterone therapy (n=14), ΔOPG levels were inversely associated with ΔSAT (r= - 0.60, p=0.03) and positively associated with ΔVAT (r=0.56, p=0.04). OPG levels decreased during testosterone therapy suggesting decreased cardiovascular risk. Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution.

Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men.

BACKGROUND: The beneficial effects of testosterone treatment (TT) are debated. METHODS: Double-blinded, placebo-controlled study of six months TT (gel) in 54 men aged 60-78 with bioavailable testosterone (BioT) <7.3 nmol/L and waist >94 cm randomized to TT (50-100 mg/day, n = 20), placebo (n = 18), or strength training (ST) (n = 16) for 24 weeks. Moreover, the ST group was randomized to TT (n = 7) or placebo (n = 9) after 12 weeks. OUTCOMES: Chemokines (MIF, MCP-1, and MIP-1 α ) and lean body mass (LBM), total, central, extremity, visceral, and subcutaneous (SAT) fat mass established by DXA and MRI. Results. From 0 to 24 weeks, MIF and SAT decreased during ST + placebo versus placebo, whereas BioT and LBM were unchanged. TT decreased fat mass (total, central, extremity, and SAT) and increased BioT and LBM versus placebo. MIF levels increased during TT versus ST + placebo. ST + TT decreased fat mass (total, central, and extremity) and increased BioT and LBM versus placebo. From 12 to 24 weeks, MCP-1 levels increased during TT versus placebo and MCP-1 levels decreased during ST + placebo versus placebo. CONCLUSION: ST + placebo was associated with decreased MIF levels suggesting decreased inflammatory activity. TT may be associated with increased inflammatory activity.

Adult glucose metabolism in extremely birthweight-discordant monozygotic twins.

AIMS/HYPOTHESIS: Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment. METHODS: Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-ß) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease). RESULTS: No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-ß, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg. CONCLUSIONS/INTERPRETATION: BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

Risk factors for fracture in elderly men: a population-based prospective study.

SUMMARY: Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as novel risk factors including frequent urination and erectile dysfunction. INTRODUCTION: Knowledge about risk factors for fracture in men is limited. The aim of this study was to evaluate factors potentially associated with fracture risk in men. METHODS: A questionnaire enquiring about potential risk factors for fractures in men was posted to a random sample of 9,314 men aged 60-74 years. A completed questionnaire was returned by 4,696 (50.4%). Follow-up on incident fractures over 5.4 years was performed using public registries. RESULTS: During the study, 203 individuals experienced a first clinical fracture, of which 85 patients were considered osteoporotic (9 in humerus, 10 vertebral, 32 in the hip and 34 in the forearm). Cox proportional hazard regression models were used to evaluate risk factors for any and osteoporotic fractures. The following variables were found to be associated with increased risk of any fracture in adjusted models family history of a hip fracture (HR; 95%CI: 1.56; 1.05-2.33), falls (2-4/year: 2.10; 1.35-3.27, >4/year: 2.46; 1.12-5.41, both compared to no falls), dizziness (2.36; 1.51-3.71), erectile dysfunction (1.41; 1.06-1.87) and frequent urination (2.06; 1.26-3.39). Similarly, falls (2.36; 1.45-3.86), dizziness (2.83; 1.52-5.25), erectile dysfunction (2.01; 1.30-3.09) and pulmonary illness (1.90; 1.03-3.53) were associated with increased risk of osteoporotic fractures in adjusted models. CONCLUSION: These results underline the importance of assessment of dizziness, falls and those with a family history of hip fracture. Frequent urination and erectile dysfunction were independently associated with increased fracture risk. Although the mechanism of association is unknown, these variables are likely to be indicators of frailty or hypogonadism.

Pattern of use of DXA scans in men: a cross-sectional, population-based study.

UNLABELLED: Osteoporosis in men is underdiagnosed. The use of dual-emission X-ray absorptiometry (DXA) was evaluated in almost 5,000 men aged 60-74 years. DXA was infrequent, despite the presence of multiple risk factors for osteoporosis and a high FRAX score. There is a need for improved targeting of DXA scans for men at high risk. INTRODUCTION: Clinical and socioeconomic factors associated with bone mass assessment (DXA) in men have seldom been evaluated. This study aimed to evaluate factors associated with the use of DXA in men. METHODS: Self-report information on prior DXA and osteoporosis risk factors were obtained from the baseline data of a study investigating the health perspectives of men aged 60-75 years. Socioeconomic and comorbidity data were retrieved from national registers. The FRAX algorithm was used to calculate the absolute fracture risk. Regression analysis was used to identify factors significantly associated with previous DXA scan. RESULTS: Of the 4,696 men returning questionnaires (50% response rate), 2.7% had prior DXA but 48% had at least one osteoporosis risk factor. Previous DXA was associated with oral glucocorticoid treatment, secondary osteoporosis, rheumatoid arthritis, fracture after age 50, falls within the previous year, smoking, and higher age. Twenty-one percent of men with prior DXA and 10% of men without prior DXA had greater than 20% risk of a major osteoporotic fracture within the next 10 years. One third of those with previous DXA had none of the FRAX osteoporosis risk factors. When family history of osteoporosis and falls were included as risk factors, 18% with previous DXA had no clinical risk factors for osteoporosis. CONCLUSIONS: DXA was infrequent in this group of elderly men, despite the presence of risk factors for osteoporosis. DXA was also used despite a low fracture risk. There is a need for improved targeting of DXA scans for men at high risk.

Prevalence of risk factors for fractures and use of DXA scanning in Danish women. A regional population-based study.

SUMMARY: To determine the relationship between risk factors and use of DXA scans. Our study showed a relatively high use of DXA in low-risk women and the relatively low coverage in women with multiple risk factors. Moreover, distance to DXA clinics, age, and socio-economic factors are associated with the use of DXA. INTRODUCTION: To determine the relationship between risk factors for fracture and use of DXA scans in Danish women in relation to distance to DXA clinics and socio-economic factors. METHODS: From the Danish National Civil Register we randomly selected 5,000 women aged 40-90 years living in the region of Southern Denmark to receive a mailed questionnaire concerning risk factors for fractures. RESULTS: The respondents rate was 84% and 77% of the invited population were available for analysis. A total of 10.3% of the women without risk factors and only 36% of the women with three or more risk factors had a history of DXA. The likelihood of a history of DXA was higher with increasing FRAX(™) 10-year risk; i.e., 8.7% and 30.2% in patients with a 10-year fracture risk of 0-14.9% and 25-100%, respectively. In women with less than 10 km to nearest DXA facility, 20.2% had a history of DXA, while 11.5% of those with more than 40 km to the nearest scanner had a history of DXA. Logistic regression analysis showed that distance, fracture risk, oral glucocorticoids, low-energy fracture, conditions associated with secondary osteoporosis, low BMI, history of falls, age 65-79 years, spouse status, and income were significantly associated with having a history of DXA. CONCLUSIONS: Our study showed a relatively high use of DXA in low-risk women and the relatively low coverage in women with multiple risk factors. Moreover, distance to DXA clinics, age, and a number of socio-economic factors are associated with the use of DXA.

Association between passive smoking in adulthood and phalangeal bone mineral density: results from the KRAM study--the Danish Health Examination Survey 2007-2008.

UNLABELLED: The study investigates an association between phalangeal bone mineral density (BMD) and self-reported passive smoking using data on 15,038 persons (aged 18-95 years), who underwent a BMD scan in the Danish KRAM study. BMD was significantly lower in persons exposed to long-term passive smoking in their home during adulthood. INTRODUCTION: Smoking is associated with decreased bone mineral density (BMD) and increased risk of osteoporotic fractures. This study aimed to investigate a possible association between BMD at the phalangeal bones and self-reported passive smoking. METHODS: The study included a cohort of 15,544 men and women aged 18-95 years, who underwent a BMD scan in the Danish KRAM study. BMD scans of the middle phalanges of the second, third and fourth digits of the non-dominant hand were performed with a compact radiographic absorptiometry system (Alara MetriScan®). Also, height, weight and body fat percentage were measured and 96.7% (n = 15,038) of the participants answered a self-reported questionnaire with information on passive smoking, other lifestyle factors, education, etc. The association between passive smoking and BMD was examined using multiple linear regression analysis. RESULTS: A total of 39.1% (n = 5,829) of the participants had been exposed to passive smoking in adulthood at home. BMD was significantly lower in subjects exposed to passive smoking, 0.343 vs. 0.331 g/cm(2); p < 0.01 (unadjusted) and 0.339 vs. 0.337 g/cm(2); p < 0.05 (adjusted for age, gender, height and weight, and smoking). Multiple linear regression analysis showed that exposure to passive smoking for more than 20 years in adulthood at home was significantly related to BMD when adjusted for potential confounders (men, ß = -4.4 × 10(-3); r = -0.05; p < 0.01 and women, ß = -2.3 × 10 (-3); r = -0.03; p < 0.05). This relationship was also seen in the group of never smokers (ß = -3.3 × 10(-3); r = -0.03; p = 0.01). CONCLUSION: Our study supports a potential negative effect of long-term passive smoking in adulthood at home on phalangeal BMD.

Polymorphisms of the peroxisome proliferator-activated receptor γ (PPARγ) gene are associated with osteoporosis.

UNLABELLED: Stimulation of PPARγ turns mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the PPARγ gene on BMD and fracture risk in two Danish cohorts and found opposing effects of certain SNPs and haplotypes in the two cohorts probably owing to environmental factors. INTRODUCTION: Stimulation of PPARγ causes development of mesenchymal stem cells to adipocytes instead of osteoblasts leading to decreased osteoblast number and BMD. The aim of this study was to examine the effect of PPARG polymorphisms on BMD and fracture risk in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for 10 years. On the basis of linkage disequilibrium between SNPs throughout the gene and previous studies we chose 10 polymorphisms for investigation. METHODS: In AROS, individuals heterozygous for the polymorphisms rs12497191, rs4135263, and rs1151999 had an increased risk of vertebral fractures (OR = 1.48-1.76, p = 0.005-0.04) compared with individuals homozygous for the common allele. In DOPS, individuals heterozygous for rs1151999 had an increased BMD at the hip sites (p ≤ 0.02). An interaction between rs1151999 and diet was found on BMD in both cohorts. RESULTS: For the polymorphism rs1152003 there was an interaction with body weight on BMD at all sites in both cohorts (p ≤ 0.07). Stratified analyses revealed that in the high weight group in AROS individuals homozygous for the variant allele had a decreased BMD (p ≤ 0.02), whereas the same pattern was found in the low weight group in DOPS (p ≤ 0.03). A number of haplotype associations were found as well, the direction of which was opposite in the two cohorts. CONCLUSION: Our study suggests an association SNPs in PPARG and haplotypes thereof and BMD and fracture risk. The effect however appears to be modifiable by environmental factors.