A genome-wide genomic score added to standard recommended stratification tools does not improve the identification of patients with very low bone mineral density.

The role of integrating genomic scores (GSs) needs to be assessed. Adding a GS to recommended stratification tools does not improve the prediction of very low bone mineral density. However, we noticed that the GS performed equally or above individual risk factors in discrimination. PURPOSE: We aimed to investigate whether adding a genomic score (GS) to recommended stratification tools improves the discrimination of participants with very low bone mineral density (BMD). METHODS: BMD was measured in three thoracic vertebrae using CT. All participants provided information on standard osteoporosis risk factors. GSs and FRAX scores were calculated. Participants were grouped according to mean BMD into very low (<80 mg/cm3), low (80-120 mg/cm3), and normal (>120 mg/cm3) and according to the Bone Health and Osteoporosis Foundation recommendations for BMD testing into an "indication for BMD testing" and "no indication for BMD testing" group. Different models were assessed using the area under the receiver operating characteristics curves (AUC) and reclassification analyses. RESULTS: In the total cohort (n=1421), the AUC for the GS was 0.57 (95% CI 0.52-0.61) corresponding to AUCs for osteoporosis risk factors. In participants without indication for BMD testing, the AUC was 0.60 (95% CI 0.52-0.69) above or equal to AUCs for osteoporosis risk factors. Adding the GS to a clinical risk factor (CRF) model resulted in AUCs not statistically significant from the CRF model. Using probability cutoff values of 6, 12, and 24%, we found no improved reclassification or risk discrimination using the CRF-GS model compared to the CRF model. CONCLUSION: Our results suggest adding a GS to a CRF model does not improve prediction. However, we noticed that the GS performed equally or above individual risk factors in discrimination. Clinical risk factors combined showed superior discrimination to individual risk factors and the GS, underlining the value of combined CRFs in routine clinics as a stratification tool.

Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. INTRODUCTION: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. METHODS: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. RESULTS: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. CONCLUSION: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

Fragility fractures and health-related quality of life: does socio-economic status widen the gap? A population-based study.

Studying 12,839 fracture cases and 91,426 controls, we found that fractures of the spine and hip are associated with clinically important HRQoL deficits up to 5 years post-fracture. Fracture cases with a low educational attainment are more likely to report very low HRQoL due to a low pre-fracture HRQoL. INTRODUCTION: The aim of this study was to explore the short-term and long-term impact of fractures on health-related quality of life (HRQoL) and to study the effect of educational attainment as a proxy for socio-economic status (SES) on post-fracture HRQoL. METHODS: In a population-based survey including 12,839 fracture cases and 91,426 controls, HRQoL was measured using the physical component score (PCS) and the mental component score (MCS) of the 12-Item Short Form Health Survey (SF-12). Information about fractures, age, sex, ethnicity, comorbidity and SES was obtained from national registers. Multiple regression analysis was conducted to measure the mean HRQoL difference, termed deficit, between non-fracture controls and fracture cases (all fractures combined and fractures at six different skeletal sites). RESULTS: PCS and MCS were significantly lower among fracture cases than among controls. Statistically and clinically important PCS deficits (≥ 5 points) were observed among people with fractures of the spine and hip up to 5 years post-fracture and among people with upper arm fractures up to 1 year post-fracture. Greater deficits were observed for MCS but not for PCS in post-fracture HRQoL in the low than in the high SES group. CONCLUSION: Fractures of the spine and hip are associated with clinically important deficits in physical HRQoL up to 5 years post-fracture. Low educational attainment widened the gap in mental but not in physical post-fracture HRQoL. However, due to low pre-fracture PCS and MCS, people with a low educational attainment and fractures were more likely to report very low HRQoL post-fracture.

The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial.

We conducted a randomized placebo-controlled double-blinded clinical trial of MK-7 or placebo daily for 3 years in postmenopausal women with osteopenia. BMD decreased at all sites without differences between the MK-7 and placebo-treated women. Changes in bone turnover markers and microstructure were similar between the two groups. INTRODUCTION: Vitamin K is a cofactor in the carboxylation of osteocalcin (OC) and carboxylated OC promotes mineralization of bone. Clinical studies suggest that vitamin K2 prevents bone loss. The aim of the study was to investigate the effect of vitamin K2 as an add-on to calcium and vitamin D supplementation on osteocalcin, bone mass, and microarchitecture in postmenopausal women. METHODS: We conducted a randomized placebo-controlled double-blinded clinical trial, including 142 postmenopausal women with osteopenia who received vitamin K2 (375 µg MK-7) or placebo daily for 3 years. Both groups received vitamin D3 (38 µg/day) and calcium (800 mg/day). We measured bone turnover markers in serum and bone mineral density and microarchitecture by DXA and HRpQCT. RESULTS: Undercarboxylated osteocalcin decreased in the MK-7-group (- 65.2 ± 23.5%) (mean ± SD) compared with the placebo group (- 0.03 ± 38.5%), p < 0.01 after 1 year. After 3 years, aBMD decreased at all sites without differences between the MK-7 and placebo-treated women (p > 0.09). aBMD decreased at the total hip by 1.5 ± 2.5% and 2.4 ± 2.7% in the MK-7 and the placebo groups, respectively, at the femoral neck by 1.5 ± 3.5% and 1.0 ± 5.0% in the MK-7 and the placebo groups, respectively, and at the lumbar spine by 1.8 ± 3.9% and 1.1 ± 3.1% in the MK-7 and the placebo groups, respectively. Changes in bone turnover markers were also similar between the two groups.We have previously reported improved microarchitecture with MK-7 after 1 year. However, changes in microstructure over 3 years were similar between the two groups, as assessed by both HRpQCT and DXA trabecular bone score. CONCLUSION: Treatment with MK-7 375 µg daily as an add-on to calcium and vitamin D increased carboxylation of osteocalcin. However, treatment of postmenopausal women with osteopenia for 3 years did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov : NCT01922804 .

A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab.

This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. INTRODUCTION: Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. METHODS: This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0-24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and ß-CTX) and safety were evaluated for 24 months, up to month 72. RESULTS: A total of 141 subjects entered the month 48-72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48-72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: - 0.8% from months 48-72; 12.8% from months 0-72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and ß-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and ß-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. CONCLUSION: A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment.

Socio-economic inequalities in fragility fracture outcomes: a systematic review and meta-analysis of prognostic observational studies.

Individuals with low socio-economic status (SES) have a higher risk of dying following hip fracture compared with individuals with high SES. Evidence on social inequalities in non-hip fractures is lacking as well as evidence on the impact of SES on health-related quality of life post fracture. INTRODUCTION: Fragility fractures, especially of the hip, cause substantial excess mortality and impairment in health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate the association between socio-economic status (SES) and post-fracture mortality and HRQoL. METHODS: PubMed, EMBASE and CINAHL databases were searched from inception to the last week of November 2018 for studies reporting an association between SES and post-fracture mortality and/or HRQoL among people aged ≥ 50 years. Risk ratios (RRs) were meta-analyzed using a standard inverse-variance-weighted random effects model. Studies using individual-level and area-based SES measures were analyzed separately. RESULTS: A total of 24 studies from 15 different countries and involving more than one million patients with hip fractures were included. The overall risk of mortality within 1-year post-hip fracture in individuals with low SES was 24% higher than in individuals with high SES (RR 1.24, 95% CI 1.19 to 1.29) for individual-level SES measures, and 14% (RR 1.14, 95% CI 1.09 to 1.19) for area-based SES measures. The quality of the evidence for the outcome mortality was moderate. Using individual SES measures, we estimated the excess HRQoL loss to be 5% (95% CI - 1 to 10%) among hip fracture patients with low SES compared with high SES. CONCLUSIONS: We found a consistently increased risk of post-hip fracture mortality with low SES across SES measures and across countries with different political structures and different health and social care infrastructures. The impact of SES on post-fracture HRQoL remains uncertain due to sparse and low-quality evidence.

Do femoral fractures in adult patients with osteogenesis imperfecta imitate atypical femoral fractures? A case series.

Atypical femoral fractures (AFFs) are low-energy femoral fractures with characteristic radiological features and a suspected relation to treatment with bisphosphonate (BP) or denosumab. In osteogenesis imperfecta (OI), BP is currently the drug of choice when medical treatment is indicated. Due to bone deformities, the radiologic appearance of femoral fractures may be different in patients with OI and patients with osteoporosis. We investigated the prevalence and appearance of femoral fractures in a cohort of adult patients with confirmed OI (55 patients, age range 19-69 years, 26 women (47%) and 35 patients (64%) had received BP treatment), who attended the outpatient clinic at Aarhus University Hospital. The fractures were evaluated according to major and minor AFF criteria. In our OI cohort, we found that eight out of 55 patients had suffered a femoral fracture in adult year: five women and three men, aged 25 to 54 years. One patient had OI type I, two had OI type III, four had OI type IV, and one had OI type V. All fractures were associated with no or minimal trauma. Four patients had fractures that fulfilled the criteria of AFFs. Two of the four patients had received long-term BP treatment prior to the fracture and three patients had severe deformities of the femur. Femoral fractures in OI imitate AFFs. This suggests that bone deformity, collagen deficiencies, and alterations in mineralization of bone may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment. Bone deformities should be monitored as part of the management of adult patients with OI. Continuous dull or aching pain in the groin or thigh should lead to radiographic examination. The radiologic appearance of femoral fractures may be different in patients with osteogenesis imperfecta (OI) and patients with osteoporosis, thus imitate atypical femoral fractures (AFF). We found that bone deformity, collagen deficiencies, and alterations in bone mineralization may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment.

Comparison of bone turnover markers in peripheral blood and bone marrow aspirate.

BACKGROUND: Bone remodeling takes place in the bone marrow environment. We investigated if levels of bone turnover markers (BTMs) differ between bone marrow and peripheral blood, if the bone marrow is an independent compartment, and how well the measurements in bone marrow correlate with bone mineral density. METHODS: Sixty-six men participated in a placebo controlled study designed to evaluate the effect of 16 weeks supplementation with resveratrol on bone mineral density and BTM. Bone marrow aspirates and blood samples were drawn at baseline and at week 16. Procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTx), osteocalcin, bone specific alkaline phosphatase (BAP), and osteoprogeterin (OPG) were analyzed. Bland-Altman analysis was used to compare measurements across compartment to detect possible systematic or proportional differences. Paired t-test was performed if no proportional difference was revealed at the difference vs concentration plot. RESULTS: Measurements of PINP, CTx, and BAP differed proportionally between compartments depending on concentration; at low concentrations absolute values were only slightly different, while at higher average concentrations the levels were much higher in bone marrow than blood. Osteocalcin measures in bone marrow were systematically and significantly lower than in blood (mean ±â€¯SD; 14.4 µg/L ±â€¯5.3 µg/L versus 21.7 µg/L ±â€¯6.0 µg/L respectively, p < 0.001). OPG measures were comparable between compartments (p = 0.69). CTx and OPG measured in blood were negatively associated with lumbar spine BMD (ß = -0.22, p = 0.05 and ß = -0.02, p = 0.02, respectively), whereas both markers measured in bone marrow were not (p = 0.60 and p = 0.50 respectively). None of the BTMs, bone marrow or blood, were associated with total hip BMD. DISCUSSION: The levels of most BTMs differed significantly between bone marrow and peripheral blood, while OPG was comparable. Levels of PINP, CTx, and BAP differed between compartments depending on concentration, suggesting bone marrow to represent a compartment separate from the general circulation. Unexpectedly, osteocalcin was lower in the marrow, a gradient that was independent of concentration. BTMs measured in bone marrow did not show any association with bone mineral density. Although further studies are needed to investigate potential explanatory causes of the differences, BTMs in bone marrow do not seem to contribute further to fracture risk assessment.

Temporomandibular disorders and psychosocial status in osteogenesis imperfecta - a cross-sectional study.

BACKGROUND: Osteogenesis Imperfecta (OI) is characterized by a number of deviations in the orofacial region. The aims of the present study were to investigate the occurrence of temporomandibular disorders, to evaluate the psychosocial status, and to assess the dental occlusion in a population of adult OI patients. METHODS: Participants (n = 75) were classified with mild OI, type I (n = 56), or moderate-severe OI, type III and IV (n = 19). OI patients were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders (axis I and II). RESULTS: Temporomandibular disorders and functional limitations in the orofacial region were rare and did not differ between patients with mild and moderate-severe OI (P > 0.050). No significant differences between Graded Chronic Pain Scale grades 0, 1, and 2 were found in mild OI vs. moderate-severe OI (P > 0.160). Few patients (16%) had signs of depression, but close to half (48%) had signs of somatization. Patients with moderate-severe OI had a lower mean number of teeth compared to patients with mild OI (P <  0.050). In general, malocclusions were prevalent, and mandibular overjet and posterior cross-bite were found more often in moderate-severe OI compared with mild (P <  0.050). CONCLUSIONS: Patients with moderate-severe OI had more malocclusions than patients with mild OI. The psychosocial status of OI patients was remarkably healthy considering the severity of this disabling systemic disorder. The bodily pain complaints frequently reported in OI patients were not largely reflected in the orofacial area as painful temporomandibular disorders.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

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.

Study description and baseline characteristics of the population enrolled in a multinational observational study of extended teriparatide use (ExFOS).

OBJECTIVE: To better characterize patients who are currently being prescribed teriparatide in Europe, this article describes the study design and baseline characteristics of participants of the Extended Forsteo * Observational Study (ExFOS). RESEARCH DESIGN AND METHODS: ExFOS is a noninterventional, multicenter, prospective, observational study in men and women with osteoporosis treated with teriparatide during the course of normal clinical practice for up to 24 months and with a post-treatment follow-up of at least 18 months. MAIN OUTCOME MEASURES: Baseline characteristics, including history of fracture and back pain, and health-related quality of life (HRQoL, assessed using the EuroQol-5 Dimension [EQ-5D]). RESULTS: Of 1607 patients enrolled, 90.9% were women. At baseline, mean (standard deviation [SD]) age was 70.3 (9.8) years, and 85.8% of patients had a history of fracture (64.7% with ≥2 fragility fractures). Of those with historic fractures, 90.8% had vertebral fractures (67.8% had thoracic fractures). The mean (SD) of reported bone mineral density T-scores were -3.0 (1.2), -2.4 (1.0), and -2.5 (0.9) for lumbar spine, total hip (left), and femoral neck (left), respectively. Overall, 39.3% of patients had experienced ≥1 fall during the 12 months before enrollment. At baseline, 11.4% of patients were osteoporosis-treatment naïve and 15% were currently using glucocorticoids. The mean (SD) visual analog scale score for back pain during the last month was 50.7 (26.9), and 62.1% of patients experienced daily or almost daily back pain. The median EQ-5D health state value at baseline was 0.62 (first and third quartiles: 0.19, 0.74). CONCLUSIONS: Baseline characteristics of the ExFOS study cohort indicate that patients prescribed teriparatide in Europe have severe osteoporosis with highly prevalent vertebral fractures, frequent and disabling back pain, and a poor HRQoL, despite previous pharmacotherapy for osteoporosis. Limitations include non-randomization, lack of a comparator group, and patient self-report for data on prior medication and fracture history.

A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk.

CONTEXT: Food ingestion decreases bone resorption, and glucose-dependent insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP have increased osteoblast activity and are rescued from age-related bone loss, whereas GIPR knockout mice have decreased cortical bone mass and compromised bone quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have higher plasma glucose 2 hours after glucose ingestion, suggesting that the variant encoding GIPR 354Gln decreases the effect of GIP. OBJECTIVE: The objective of the study was to investigate the effect of GIPR Glu354Gln on bone mineral density (BMD) and fracture risk. DESIGN: This was a prospective, comprehensive, cohort study (number NCT00252408). PARTICIPANTS: A total of 1686 perimenopausal women were included. MAIN OUTCOME MEASURES: Dual-energy X-ray absorptiometry was performed at baseline and after 10 years. Incident fractures were recorded during the follow-up and were obtained from the Danish National Patient Registry, giving a total follow-up time of a minimum 16 years. RESULTS: After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had significantly lower BMD at the femoral neck compared with carriers of the major G-allele (CC: 0.755 ± 0.015 g/cm(2) vs CG: 747 ± 0.005 g/cm(2); GG: 0.766 ± 0.004 g/cm(2), P < .001). Correspondingly, total hip BMD was significantly lower among C allele carriers (CC: 0.881 ± 0.016 g/cm(2); CG: 0.884 ± 0.005 g/cm(2); and GG: 0.906 ± 0.004 g/cm(2), P < .001). Finally, women homozygous for the variant C allele had an increased risk (hazard ratio 1.6, confidence interval 1.0-2.6, P < .05) of nonvertebral fractures. CONCLUSION: This study demonstrates an association between a functional GIPR polymorphism Glu354Gln (rs1800437) and BMD and fracture risk. These findings further establish GIP to be involved in the regulation of bone density.

Effectiveness and characteristics of multifaceted osteoporosis group education--a systematic review.

UNLABELLED: The characteristics and effectiveness of osteoporosis multifaceted group education were determined from a systematic review of international literature. Findings showed that these educational programmes may be beneficial in a variety of important factors for the prevention, treatment and management of osteoporosis. INTRODUCTION: This systematic review investigated quantitative studies on osteoporosis multifaceted group education. The purpose was to investigate the characteristics as well as the effectiveness of this form of osteoporosis patient education. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided this systematic review. Relevant databases were searched until January 2013. RESULTS: Seven studies published between 1993 and 2011 including osteoporosis patients with or without fractures were found. The multifaceted educational programmes all consisted of three overall themes: (1) Knowledge of osteoporosis, (2) Medication and diet and (3) Exercise, but with different foci across the studies. Overall, 24 outcome measures representing six topics were applied: (1) Health-related quality of life, (2) Psychosocial function, (3) Pain, (4) Physical activity, (5) Knowledge and (6) Medication and diet. The review showed that multifaceted osteoporosis group education can increase the patients' knowledge of osteoporosis as well as their health-related quality of life, physical activity and psychosocial functioning. It has the potential to increase adherence to both pharmacological and non-pharmacological treatments. CONCLUSIONS: Multifaceted group education may have a positive impact on the patients' ability to engage in preventing and managing osteoporosis. Further research directed towards the complexity of multifaceted group education is needed. In addition, research investigating the educational needs of specific groups of osteoporotic patients is required.

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.

Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis.

UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three of these polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted to investigate the effect of these polymorphisms on BMD and risk of vertebral fractures in a case-control study including 798 individuals. METHODS: Genotyping was carried out using TaqMan assays. BMD was measured using dual energy X-ray absorptiometry, and vertebral fractures were assessed by lateral spinal X-rays. RESULTS: The rare allele of a splice site polymorphism, 151 + 1: G-T, was associated with increased fracture risk and reduced BMD in women. Two other loss-of-function polymorphisms, Glu496Ala and Gly150Arg, were also associated with BMD. The Glu496Ala variant allele was associated with decreased lumbar spine BMD in women and decreased total hip BMD in men. The 150Arg allele was associated with decreased total hip BMD in women and men combined. The minor allele of the gain-of-function polymorphism, Ala348Thr, was associated with reduced fracture risk and increased BMD at all sites in men. The Gln460Arg variant allele, which has been associated with increased receptor function in monocytes, was associated with increased total hip BMD in women. With the exception of His155Tyr for which we found conflicting results in men and women, our results are consistent with the phenotype of the knockout mouse. Analysis of a haplotype containing Ala348Thr, Gln460Arg, and Glu496Ala showed that the effects of the haplotypes on BMD and fracture were driven by Ala348Thr in men and by Gln460Arg and Glu496Ala in women. CONCLUSION: In conclusion, we found that functional polymorphisms in the P2X(7) receptor gene and haplotypes containing three of these polymorphisms are associated with osteoporosis.

An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

Diagnosis and management of primary hyperparathyroidism in Europe.

BACKGROUND: There is continued debate as to the optimal strategy for diagnosis and management of primary hyperparathyroidism (PHPT). AIM: To compare the strategies used for the diagnosis and management of PHPT by physicians in five European countries. DESIGN: Questionnaire-based survey. METHODS: Physicians in France, Germany, the UK, Italy and Spain were invited to participate in the survey which was conducted using a web-based interface and were included in the evaluation if they had treated a minimum of four patients suffering from PHPT in the past year. RESULTS: A total of 421 physicians completed the survey. The majority of respondents were endocrinologists (68%) but other specialities included rheumatologists (10.9%), internists (11.8%) and urologists (9.2%). Diagnostic methods were similar across different countries and specialities but there were significant differences in the proportion of physicians who recommended parathyroidectomy in asymptomatic patients with indications for surgery according to the 2002 National Institutes of Health (NIH) consensus conference statement (χ(2 )= 26.1, P < 0.001). The proportion of patients referred for surgery ranged from 32% in Italy to 66% in Spain with intermediate values in Germany (64%), France (55%) and the UK (53%). Conversely, pharmacological therapy was used most frequently for these patients in Italy (32%) and least frequently in Spain (14%). CONCLUSION: Significant differences exist in the management of patients with asymptomatic PHPT in countries across Europe who have accepted indications for surgery according to the NIH consensus statement. Further research will be required to explore the reasons for this and to determine if these differences affect the clinical outcome of PHPT.