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Summary: The effect of deprivation on total bone health status has not been well defined. We examined the relationship between socioeconomic deprivation and poor bone health and falls and we found a significant association. The finding could be beneficial for current public health strategies to minimise disparities in bone health. Purpose: Socioeconomic deprivation is associated with many illnesses including increased fracture incidence in older people. However, the effect of deprivation on total bone health status has not been well defined. To examine the relationship between socioeconomic deprivation and poor bone health and falls, we conducted a cross-sectional study using baseline measures from the United Kingdom (UK) Biobank cohort comprising 502,682 participants aged 40–69 years at recruitment during 2006–2010. Method: We examined four outcomes: 1) low bone mineral density/osteopenia, 2) fall in last year, 3) fracture in the last five years, and 4) fracture from a simple fall in the last five years. To measure socioeconomic deprivation, we used the Townsend index of the participant's residential postcode. Results: At baseline, 29% of participants had low bone density (T-score of heel < -1 standard deviation), 20% reported a fall in the previous year, and 10% reported a fracture in the previous five years. Among participants experiencing a fracture, 60% reported the cause as a simple fall. In the multivariable logistic regression model after controlling for other covariates, the odds of a fall, fracture in the last five years, fractures from simple fall, and osteopenia were respectively 1.46 times (95% confidence interval [CI] 1.42–1.49), 1.26 times (95% CI 1.22–1.30), 1.31 times (95% CI 1.26–1.36) and 1.16 times (95% CI 1.13–1.19) higher for the most deprived compared with the least deprived quantile. Conclusion: Socioeconomic deprivation was significantly associated with poor bone health and falls. This research could be beneficial to minimise social disparities in bone health. [ABSTRACT FROM AUTHOR]

Purpose: The association between type 2 diabetes mellitus (T2DM), lifestyle factors, and the risk of osteoporosis (OP) is well-established. However, the impact of a healthy lifestyle on diabetes-related osteoporosis needs further investigation. Our objective was to explore if a combination of healthy lifestyle factors could mitigate the risk of OP in individuals with type 2 diabetes. Methods: This longitudinal analysis included 237,725 middle-aged and older participants. An overall lifestyle score, ranging from 0 to 7, was calculated by assigning a point for each of the seven healthy lifestyle factors, including no current smoking, non-excessive alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and adequate sunshine exposure. Results: During a median follow-up 12.21 years, 5760 OP cases were documented. Participants with T2DM showed a higher risk of OP than those without diabetes. Compared with participants without diabetes who had a lifestyle score of 6–7, the hazard ratios (HRs) for OP were 1.58 (95% CI 1.23–2.03), 1.62 (95% CI 1.16–2.25), and 2.58 (95% CI 1.64–4.05) for participants with T2DM who had a lifestyle score of 4, 3, and 0–2, respectively. There was a graded association between higher lifestyle scores and lower risks of incident OP among participants without diabetes as well as among those with T2DM. We estimated that the population attributable fraction for not adhering to 6–7 lifestyle behaviors was 15.7%. Conclusions: Participants with T2DM who adhered to a variety of healthy lifestyle factors demonstrated a substantially reduced risk of developing OP. [ABSTRACT FROM AUTHOR]

Summary: Bone mineral density (BMD) is an essential predictor of osteoporosis and fracture. We conducted a genome-wide trajectory analysis of BMD and analyzed the BMD change. Purpose: This study aimed to identify the genetic architecture and potential biomarkers of BMD. Methods: Our analysis included 141,261 white participants from the UK Biobank with heel BMD phenotype data. We used a genome-wide trajectory analysis tool, TrajGWAS, to conduct a genome-wide association study (GWAS) of BMD. Then, we validated our findings in previously reported BMD genetic associations and performed replication analysis in the Asian participants. Finally, gene-set enrichment analysis (GSEA) of the identified candidate genes was conducted using the FUMA platform. Results: A total of 52 genes associated with BMD trajectory mean were identified, of which the top three significant genes were WNT16 (P = 1.31 × 10−126), FAM3C (P = 4.18 × 10−108), and CPED1 (P = 8.48 × 10−106). In addition, 114 genes associated with BMD within-subject variability were also identified, such as AC092079.1 (P = 2.72 × 10−13) and RGS7 (P = 4.72 × 10−10). The associations for these candidate genes were confirmed in the previous GWASs and replicated successfully in the Asian participants. GSEA results of BMD change identified multiple GO terms related to skeletal development, such as SKELETAL SYSTEM DEVELOPMENT (Padjusted = 2.45 × 10−3) and REGULATION OF OSSIFICATION (Padjusted = 2.45 × 10−3). KEGG enrichment analysis showed that these genes were mainly enriched in WNT SIGNALING PATHWAY. Conclusions: Our findings indicated that the CPED1-WNT16-FAM3C locus plays a significant role in BMD mean trajectories and identified several novel candidate genes contributing to BMD within-subject variability, facilitating the understanding of the genetic architecture of BMD. [ABSTRACT FROM AUTHOR]

Summary: We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. Purpose: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. Methods: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. Results: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. Conclusion: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare. [ABSTRACT FROM AUTHOR]

Summary: The potential of bone mineral density (BMD)-related genome-wide polygenic score (PGS) in identifying individuals with a high risk of fractures remains unclear. This study suggests that an efficient PGS enables the identification of strata with up to a 1.5-fold difference in fracture incidence. Incorporating PGS into clinical diagnosis is anticipated to increase the population-level screening benefits. Purpose: This study sought to construct genome-wide polygenic scores for femoral neck and total body BMD and to estimate their potential in identifying individuals with a high risk of osteoporotic fractures. Methods: Genome-wide polygenic scores were developed and validated for femoral neck and total body BMD. We externally tested the PGSs, both by themselves and in combination with available clinical risk factors, in 455,663 European ancestry individuals from the UK Biobank. The predictive accuracy of the developed genome-wide PGS was also compared with previously published restricted PGS employed in fracture risk assessment. Results: For each unit decrease in PGSs, the genome-wide PGSs were associated with up to 1.17-fold increased fracture risk. Out of four studied PGSs, P G S _ T B B M D 81 (HR: 1.03; 95%CI 1.01–1.05, p = 0.001) had the weakest and the P G S _ T B B M D l d p r e d (HR: 1.17; 95%CI 1.15–1.19, p < 0.0001) had the strongest association with an incident fracture. In the reclassification analysis, compared to the FRAX base model, the models with P G S _ F N B M D 63 , P G S _ T B B M D 81 , P G S _ F N B M D l d p r e d , and P G S _ T B B M D l d p r e d improved the reclassification of fracture by 1.2% (95% CI, 1.0 to 1.3%), 0.2% (95% CI, 0.1 to 0.3%), 1.4% (95% CI, 1.3 to 1.5%), and 2.2% (95% CI, 2.1 to 2.4%), respectively. Conclusions: Our findings suggested that an efficient PGS estimate enables the identification of strata with up to a 1.7-fold difference in fracture incidence. Incorporating PGS information into clinical diagnosis is anticipated to increase the benefits of screening programs at the population level. [ABSTRACT FROM AUTHOR]

Summary: To explore the association of air pollution and hip fracture and related mortality in the UK. The average levels of PM2.5, PM10, and NO2 exhibited a positive association with hip fracture and short-term mortality while O3 did not. Our study highlights the association of air pollution and hip fracture. Introduction: Until now, the influence of air pollution on bone mineral density and associated fractures has drawn little attention, and the consequences are controversial. To investigate the association between air pollution and hip fracture incidence and related short-term mortality. Methods: We constructed a cohort of all the National Hip Fracture Database beneficiaries (513,540 patients) in the UK from 2013 to 2018. Per year averages of PM2.5, PM10, O3, NO2, and SO2 were estimated according to the person's residence. The incidence rate ratio with 95% confidence interval and all-cause mortality within 30-day post-fracture (ACM30D) rate ratios were estimated using generalized additive models. Results: The average levels of PM2.5, PM10, and NO2 exhibited a positive association with the incidence rate of hip fracture (IHF) and ACM30D. Whereas, this association was negative for O3 levels. Each increase of 5 μg per cubic meter in PM2.5, PM10, and NO2 leads to 9.5%, 9.2%, and 4.1% higher hip fracture rate, respectively, and also 9.3%, 8.3%, and 2.9% higher ACM30D, respectively. When we restricted the analysis to low-level exposure of air pollutants, similar results were obtained. Conclusion: Our study found a moderate, positive association between IHF, ACM30D, and the levels of specific air pollutants in the entire National Hip Fracture Database population. A reduction in the levels of PM2.5, PM10, and NO2 may decrease the hip fracture incidence rate and associated short-term mortality in older adults. Our study highlights the influence of air pollution on hip fracture. [ABSTRACT FROM AUTHOR]

Summary: We described physical function and activity in UK adults with X-linked hypophosphatemia (XLH). Our data indicate that low physical activity and impaired mobility are common in adults with XLH. Deficits in lower limbs muscle power and functional capacity contribute to the loss of physical function in adults with XLH. Introduction: There is a dearth of literature on physical function and physical activity in adults with X-linked hypophosphatemia (XLH). We described muscle strength and power, functional capacity, mobility and physical activity level and explored the relationships among these variables in adults with XLH. Methods: Participants were recruited as part of a UK-based prospective cohort study, the RUDY Study. They underwent a clinical visit and physical examination, including assessment of handgrip strength, jump power (mechanography), six-minute walk test (6MWT) and short physical performance battery (SPPB), and completed the International Physical Activity Questionnaire (IPAQ). Performance data were analysed using parametric and non-parametric tests, whereas correlations were assessed by univariate analysis. Results: Twenty-six adults with XLH (50% males) with a mean age of 44 ± 16.1 years were recruited. Jump power and 6MWT distances (p < 0.0001) were 54.4% and 38.6% lower respectively in individuals with XLH compared with normative values. These deficits were not associated with age or sex. Handgrip strength values were similar to expected values. Deficits in muscle power were more pronounced than those reported at 6MWT (p < 0.0001). Univariate analysis revealed only a correlation between total physical activity and muscle power (r = 0.545, p = 0.019). Conclusions: Adults with XLH have a marked deficit in lower limb muscle power and a reduced functional capacity, with a high incidence of impaired mobility and inactivity. In addition to metabolic effects of XLH, low physical activity may contribute to deficits in lower limb power. Further studies are required to develop novel treatment approaches to improve physical function and mobility. [ABSTRACT FROM AUTHOR]

Summary: Additional physiotherapy in the first postoperative week was associated with fewer days to discharge after hip fracture surgery. A 7-day physiotherapy service in the first postoperative week should be considered as a new key performance indicator in evaluating the quality of care for patients admitted with a hip fracture. Introduction : To examine the association between physiotherapy in the first week after hip fracture surgery and discharge from acute hospital. Methods: We linked data from the UK Physiotherapy Hip Fracture Sprint Audit to hospital records for 5395 patients with hip fracture in May and June 2017. We estimated the association between the number of days patients received physiotherapy in the first postoperative week; its overall duration (< 2 h, ≥ 2 h; 30-min increment) and type (mobilisation alone, mobilisation and exercise) and the cumulative probability of discharge from acute hospital over 30 days, using proportional odds regression adjusted for confounders and the competing risk of death. Results: The crude and adjusted odds ratios of discharge were 1.24 (95% CI 1.19–1.30) and 1.26 (95% CI 1.19–1.33) for an additional day of physiotherapy, 1.34 (95% CI 1.18–1.52) and 1.33 (95% CI 1.12–1.57) for ≥ 2 versus < 2 h physiotherapy, and 1.11 (95% CI 1.08–1.15) and 1.10 (95% CI 1.05–1.15) for an additional 30-min of physiotherapy. Physiotherapy type was not associated with discharge. Conclusion: We report an association between physiotherapy and discharge after hip fracture. An average UK hospital admitting 375 patients annually may save 456 bed-days if current provision increased so all patients with hip fracture received physiotherapy on 6–7 days in the first postoperative week. A 7-day physiotherapy service totalling at least 2 h in the first postoperative week may be considered a key performance indicator of acute care quality after hip fracture. [ABSTRACT FROM AUTHOR]

Summary: We estimated and characterized the imminent fracture risk (1–2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older individuals with newly diagnosed osteoporosis and individuals who had a fracture while on treatment with a bisphosphonate were at a high risk of imminent fracture. Purpose: To characterize and estimate 1- to 2-year fracture risk in high-risk fracture patients. Methods: Multi-cohort study in (database/study period) UK (CPRD/1995–2017), Spain (SIDIAP/2006–2016) and Denmark (DHR/1995–2016) including individuals ≥ 50 years old in NDO (newly diagnosed osteoporosis), OFx (incident osteoporotic fracture), BP (incident oral bisphosphonates use) or FWOT (fracture while on treatment with bisphosphonates). Outcomes (ICD-10/READ): hip, clinical spine, non-hip, non-spine and hip/humerus/distal forearm fracture. Follow-up: from cohort entry until death, migration/transfer or end of the study. Statistics: baseline characteristics and incidence rate (IR per 1000 persons). Results (1-year IR): NDO included 69,899 (UK), 37,901 (Spain) and 158,191 (Denmark) individuals. Spanish-IR was lowest for hip (4.7), clinical spine (2.5) and major osteoporotic fracture (MOF) (17.3) and highest in Denmark (74.2, 26.0 and 120.1, respectively). OFx included 83,514 (UK), 51,044 (Spain) and 509,551 (Denmark) individuals. IR in Denmark was highest for hip (24.1) and MOF (47.2), in Spain was highest for the clinical spine (9.4) and lowest for hip (9.5) and in the UK was lowest for the clinical spine (2.8) and MOF (20.7). BP included 148,507 (UK), 52,037 (Spain) and 204,010 (Denmark) individuals. Spanish-IR was lowest for hip (5.0) and MOF (21.1) and highest in Denmark (20.3 and 48.6, respectively). FWOT included 28,930 (UK), 1,865 (Spain) and 31,882 (Denmark) individuals. Clinical spine-IR was highest for Spain (12.0). Hip-IR was lowest for Spain (7.6) and highest for Denmark (33.6). Comparing young subjects, those who have FWOT started with an increased fracture rate. Conclusion: OFx and FWOT individuals experience higher re-fracture incidence rates than those with osteoporosis with or without treatment. [ABSTRACT FROM AUTHOR]

Summary: Less is known about the risk of fracture in people with rheumatoid arthritis aged under 50 than those in older age groups. The study shows that the risk of fracture before age 50 remains significantly higher in those with rheumatoid arthritis than matched controls. This has implications for fracture risk management. Introduction: To determine the risk of first and subsequent fracture occurring before age 50 in people diagnosed with rheumatoid arthritis (RA) before age 50. Methods: A retrospective observational cohort study of RA cases with matched controls using data from Clinical Practice Research Datalink (CPRD) of adults ≥ 18 years with diagnosis of RA recorded from 1992 to 2016 in the UK. Patients were followed from index date to the first fracture and subsequent fracture. A total of 36,858 cases were each matched to 3 controls. Incidence rates (IR) and incidence rate ratios (IRR) of first and subsequent fractures were calculated. A multivariate Cox's proportional hazards model was used to calculate the risk of first fracture and of subsequent fracture in the presence of different risk factors. Results: The IR of first and subsequent fractures at any age is significantly higher in cases than controls for patients with onset of RA at any age. This includes first fractures occurring before age 50 for those diagnosed with RA before this age. In women, the rate of first fracture before age 50 are significantly higher than matched controls (IRR 1.29 CI 1.12–1.49), the IRR for subsequent fracture is higher but not significantly so. For men, the IRRs of first and subsequent fractures below age 50 are also higher but not significantly so. Gender, previous fracture, glucocorticoid prescription, osteoporosis diagnosis, alcohol, smoking, and bisphosphonate prescription have a significant effect on the risk of first fracture at any age for RA patients; all these variables except osteoporosis diagnosis and alcohol have a significant effect on the risk of subsequent fracture and first fractures before age 50. Conclusions: These results indicate an increased risk of first fracture before age 50 in people with RA diagnosed before this age. It is important that patients with RA of all ages are given timely support from the time of diagnosis to protect their bone health. [ABSTRACT FROM AUTHOR]

Summary: We describe the physical function in adults with osteogenesis imperfecta (OI) and explored clinical and non-clinical factors related to its impairment. Our data showed that physical dysfunction is a common feature of adults with OI, varying by OI severity, and mediated by the presence and quality of pain and fatigue symptoms. Introduction: There is a paucity of data describing physical function in adults with osteogenesis imperfecta (OI). We investigated the effects of OI and its severity on physical function and explored the relationship between physical function and number of fractures and symptomatology. Methods: Adults with OI of different types were recruited from the RUDY study, an ongoing UK-based prospective cohort study. Participants completed demographic and clinical questions and questionnaires. These assessed physical function (SF-36), mobility (EQ-5D-5L and NEADL), fatigue (FACIT-F), and pain (SF-MQ-2). Scores were compared using parametric or non-parametric statistical analyses, whereas correlations between outcomes were examined using univariate and multivariate regression analysis. Results: Seventy-eight adults with OI aged 43.5 ± 14.5 years were enrolled (type I, 32; type III, 11; type IV, 10; unknown type, 26). Physical function (PCS, SF-36) was significantly lower in all participants than normative values (p < 0.001) and in type III than type I (p = 0.008). Mobility was significantly different across the types (EQ-5D-EL, p = 0.007; NEADL, p < 0.001), with type III having more severe problems, followed by types IV, unknown, and I. Physical function was associated with OI type (r = 0.26; p = 0.021), presence and quality of pain (r = − 0.57; p < 0.0001), and fatigue (r = − 0.51; p < 0.0001). Multivariate analysis revealed that physical function correlated independently with age, OI type, fatigue, and non-neuropathic pain. Conclusions: Individuals with OI display a marked deterioration in physical function during adulthood. This impairment varies in severity according to the OI phenotype and is associated with the presence of non-neuropathic pain and fatigue. [ABSTRACT FROM AUTHOR]

Summary: Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits. Introduction: Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS. Methods: We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively. Results: SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10−8) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10−10, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10−8, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development. Conclusion: Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture. [ABSTRACT FROM AUTHOR]

Summary: This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88–90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed. Introduction: Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015. Methods: This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture. Results: A total of 648,369 fracture patients were included. Mean age 70.2–78.9 years; 22.2–31.7% were men. In Denmark, the treatment gap was stable at approximately 88–90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap—though never smaller than 63%—was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women. Conclusion: Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years. [ABSTRACT FROM AUTHOR]

Summary: Chronic kidney disease (CKD) is a risk factor for fractures. However, in hip fracture patients, CKD G3-G5 was associated with a higher mortality risk and not associated with a higher risk of subsequent non-hip fractures compared to eGFR > 60 ml/min. The higher mortality risk may, as competing risk, explain our findings. Introduction: Chronic kidney disease (CKD) is a known risk factor for fragility fractures. Patients aged 50+ with a recent fragility fracture have an increased risk of subsequent fractures. Our aim was to evaluate the association between CKD stages G3–G5 versus estimated glomerular filtration rate (eGFR) > 60 ml/min and the risk of a new non-hip fracture or fragility fracture in patients with a first hip fracture. Methods: Population-based cohort study using the UK general practices in the Clinical Practice Research Datalink. Associations between CKD stage and first subsequent fracture were determined using Cox proportional hazard analyses to estimate hazard ratios (HRs). To explore the potential competing risk of mortality, cause-specific (cs) HRs for mortality were estimated. Results: CKD G3–G5 was associated with a lower risk of any subsequent non-hip fracture (HR: 0.90, 95%CI: 0.83–0.97), but not with the risk of subsequent major non-hip fragility fracture. CKD G3-G5 was associated with a higher mortality risk (cs-HR: 1.05, 95%CI: 1.01–1.09). Mortality risk was 1.5- to 3-fold higher in patients with CKD G4 (cs-HR: 1.50, 95%CI: 1.38–1.62) and G5 (cs-HR: 2.93, 95%CI: 2.48–3.46) compared to eGFR > 60 ml/min. Conclusions: The risk of a subsequent major non-hip fragility fractures following hip fracture was not increased in patients with CKD G3–G5 compared to eGFR > 60 ml/min. Mortality risk was higher in both hip fracture and non-hip fracture patients with CKD G4 and G5. The higher mortality risk may, as competing risk, explain our main finding of no increased or even decreased subsequent fracture risk after a hip fracture in patients with CKD G3–G5. [ABSTRACT FROM AUTHOR]

Summary: Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving osteoporosis medications in the UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, long-term treatment persistence must be improved. Introduction: Persistence with osteoporosis therapies has historically been poor. To treat this chronic and progressive disease, it is essential that patients receive the full benefit of these medications. We estimated persistence and compliance with osteoporosis therapies in a large sample of postmenopausal women in the UK. Methods: Data were obtained from the Clinical Practice Research Datalink for all women aged 50 years and over or women with early menopause, who received at least one prescription in primary care for any licensed osteoporosis therapy between January 1, 2010 and December 31, 2015. Persistence and compliance at 24 months (primary objective) and at 5 years (exploratory objective) were estimated in three patient cohorts: "All Patients," "Naïve Patients," and "Drug-Specific." Results: The All Patients cohort included 72,256 women. Persistence with any therapy was 56.1%, 43.6%, 36.4%, and 31.0% at 6, 12, 18, and 24 months, respectively, and 23.2% and 13.1% at 3 years and 5 years, respectively. Patients were generally more persistent and compliant if evaluated from their first exposure to osteoporosis therapy (Naïve Patients cohort). In the drug-specific analysis, 64% of patients receiving denosumab (administered subcutaneously every 6 months) were persistent at 24 months compared with 28% and 23% of those taking oral bisphosphonates and intravenous bisphosphonates, respectively. Conclusions: Only about one in three patients who received osteoporosis therapy continued to be on treatment after 2 years. There is a need to improve persistence with osteoporosis therapy, especially for high-risk patients [ABSTRACT FROM AUTHOR]

Summary: Little is known about the long-term impact of vertebral fractures on physical activity. There is also uncertainty over the clinical significance of mild vertebral fracture. We showed that women with moderate/severe but not mild vertebral fracture do less walking duration and housework than those without fracture after 5.4 years of follow-up.Introduction: Little is known about the long-term impact of vertebral fractures on physical activities. There is also uncertainty over the clinical significance of mild fracture. Therefore, the aim of this study was to evaluate the prospective association between vertebral fracture and future physical activity.Methods: This is a 5-year prospective study of a mixed community and secondary care cohort of women aged > 50 from the UK. Vertebral fractures were identified at baseline on radiographs or DXA-based Vertebral Fracture Assessment by a Quantitative Morphometric approach and defined as moderate/severe (≥ 25% height decrease) or mild (20-24.9% height decrease). Physical activity data were collected 5.4 years later by self-completion questionnaires. Multivariable logistic regression was used to determine the association between presence of fracture and various physical activities while adjusting for potential confounders.Results: Two hundred eighty-six women without, 58 with mild, and 69 with moderate/severe fracture were recruited. Those with mild and moderate/severe fracture were older than women without fracture and had more concomitant diseases at baseline. At 5.4 years follow-up, women with moderate/severe fracture self-reported shorter walking duration compared to those without fracture, even after adjusting for potential confounders (OR 2.96, 95%CI 1.11-7.88, P = 0.030). No independent association was seen between the presence of mild fractures and reduced physical activity at follow-up.Conclusion: This is the first study of older women from the UK that explored the prospective association between vertebral fracture and physical activity duration. Moderate/severe fractures were associated with reduced walking duration. Mild fractures had no impact on future physical ability. [ABSTRACT FROM AUTHOR]

Summary: In the present retrospective case-control study, we compared 6485 women with fractures and 6485 women without fractures from 135 general practitioner offices in the UK. Women without bone fractures were statistically more likely to have been exposed to oral contraception, depending on their age and therapy duration. Introduction: The aim of this analysis was to compare the risk of bone fracture in women using hormonal contraception with that in women who have never used hormonal contraception. Methods: A total of 6485 women (mean age 37.8 years) with an initial diagnosis of fracture between January 2010 and December 2015 were identified in 135 doctors' offices in the UK Disease Analyzer database. In this nested case-control study, each case with a fracture was matched (1:1) to a control without a fracture for age, index year, and follow-up time. In total, 12,970 individuals were available for analysis. The main outcome of the study was the risk of fracture as a function of combined oral contraceptive (OC) therapy. Multivariate logistic regression models were used to determine the effect of OC therapy and its duration on the risk of fracture in the entire population and in four age-specific subgroups. Results: Women without bone fractures were significantly more likely to have used oral contraception (OR 0.81). The usage of oral contraception was associated with a significantly lower risk of bone fracture (OR 0.81, 95% CI 0.74-0.90). This effect was strongest in the age groups 18-25 and 26-35 and in patients with an OC treatment duration of more than 1 year. Conclusions: The present study revealed that women without bone fractures were significantly more likely to have had exposure to combined oral contraception, especially where the duration of intake was at least 5 years. [ABSTRACT FROM AUTHOR]

Summary: Fragility fractures of the hip have a major impact on the lives of patients and their families. This study highlights significant geographical variation in secondary fracture prevention with even the highest performing regions failing the majority of patients despite robust evidence supporting the benefits of diagnosis and treatment. Introduction: The purpose of the study is to describe the geographic variation in anti-osteoporosis drug therapy prescriptions before and after a hip fracture during 1999-2013 in the UK. Methods: We used primary care data (Clinical Practice Research Datalink) to identify patients with a hip fracture and primary care prescriptions of any anti-osteoporosis drugs prior to the index hip fracture and up to 5 years after. Geographic variations in prescribing before and after availability of generic oral bisphosphonates were analysed. Multivariable logistic regression models were adjusted for gender, age and body mass index (BMI). Results: Thirteen thousand sixty-nine patients (76 % female) diagnosed with a hip fracture during 1999-2013 were identified. Eleven per cent had any anti-osteoporosis drug prescription in the 6 months prior to the index hip fracture. In the 0-4 months following a hip fracture, 5 % of patients were prescribed anti-osteoporosis drugs in 1999, increasing to 51 % in 2011 and then decreasing to 39 % in 2013. The independent predictors (OR (95 % CI)) of treatment initiation included gender (male 0.42 (0.36-0.49)), BMI (0.98 per kg/m increase (0.97-1.00)) and geographic region (1.29 (0.89-1.87) North East vs. 0.56 (0.43-0.73) South Central region). Geographic differences in prescribing persisted over the 5-year follow-up. If all patients were treated at the rate of the highest performing region, then nationally, an additional 3214 hip fracture patients would be initiated on therapy every year. Conclusions: Significant geographic differences exist in prescribing of anti-osteoporosis drugs after hip fracture despite adjustment for potential confounders. Further work examining differences in health care provision may inform strategies to improve secondary fracture prevention after hip fracture. [ABSTRACT FROM AUTHOR]

Summary: Dickkopf-related protein 1 (DKK1) is a major inhibitor of Wnt signalling pathway but also plays an important role in bone formation. Its circulating levels appear to correlate significantly with plasma levels of inflammatory factors, fractalkine and IL-6. This study, using a large sample of UK twins, showed that the variation of each of these factors and correlation between them was explained by the genetic factors, and indicated possible association with DKK1 gene variants. Introduction: DKK1 is involved in the development of several inflammatory conditions related to bone and joint degradation. Our objectives were to explore the genetic contribution (heritability) to circulating DKK1 variation and its correlation with other inflammatory cytokines, interleukin 6 (IL-6) and fractalkine, and to test whether the DKK1 heritability could be attributable to single nucleotide polymorphisms (SNPs) mapped to DKK1, IL- 6 and FRCT genes. Methods: The study included a large community-based sample of 4939 women drawn from the general UK population. Plasma samples were analysed for circulating levels of DKK1, IL-6 and fractalkine (FRCT); 65 SNPs of DKK1, IL- 6 and FRCT candidate genes, with MAF >0.1, were examined. We applied variance component analysis to evaluate contribution of putative genetic (including above SNPs) and environmental factors to variation of DKK1, and its correlation with IL-6 and FRCT. Results: Putative genetic factors explained 42.2 ± 2 % of the total variation of circulating DKK1 levels, and were also significant for fractalkine and IL-6 variations. Most importantly, we report significant phenotypic (0.208 ± 0.006-0.459 ± 0.007) and genetic (0.338 ± 0.069-0.617 ± 0.033) correlations between these molecules. We found evidence suggestive of association between the DKK1 and its structural genes variants. Conclusions: Circulating DKK1 levels correlated significantly with levels of IL-6 and FRCT, known risk factors for several inflammatory processes suggesting a potential role of DKK1 in inflammation and tissue injury. Our results suggest the contribution of genetic factors in inter-individual variation of DKK1 levels in human population. However, further studies are required to determine genetic polymorphisms affecting DKK1 variation and its correlation with IL-6 and FRCT. [ABSTRACT FROM AUTHOR]

Summary: The probability of initiating with anti-osteoporosis therapy increased from 7 % in 2000 to 46 % in 2010. This improvement was greater for patients over the age of 75 years. Men, those overweight, having dementia or exposed to antipsychotics, sedatives/hypnotics or opioid analgesics were significantly less likely to receive anti-osteoporosis drugs. Introduction: The objective of this study was to examine trends and determinants of anti-osteoporosis drug prescribing after hip fracture in the UK between 2000 and 2010. Methods: Data were extracted from the UK Clinical Practice Research Datalink for patients ≥50 years who had a first hip fracture between 2000 and 2010 and who did not currently (≤6 months prior) receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid hormone, calcitonin and raloxifene) ( n = 27,542). The cumulative incidence probability of being prescribed anti-osteoporosis drugs within 1 year after hip fracture was estimated by Kaplan-Meier life-table analyses. Determinants for treatment initiation were estimated by Cox proportional hazards models. Results: The probability of being prescribed any anti-osteoporosis drug after hip fracture increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in patients ≥75 years. The increase in prescribing of anti-osteoporosis drugs was complemented by a similar increase in vitamin D/calcium provision. Cumulative incidence of receiving anti-osteoporosis therapy was greater at any given point in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 % in 2010). In addition to male gender, multivariable Cox regression identified reduced likelihood of receiving anti-osteoporosis drugs for those being overweight, having dementia and exposed to psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics. Conclusion: Although the prescribing of anti-osteoporosis drugs after hip fracture has increased substantially since 2000, the overall rate remained inadequate, particularly in men. With the continuing increase in the absolute number of hip fractures, further research should be made into the barriers to optimise osteoporosis management. [ABSTRACT FROM AUTHOR]

Summary: Predictors of 25(OH)D half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D half-life may be applied as a tool to investigate vitamin D expenditure. Introduction: The aim of this study was to investigate predictors of 25(OH)D half-life and plasma 25(OH)D concentration. Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D was measured in healthy men aged 24-39 years, resident in The Gambia, West Africa ( n = 18) and in the UK during the winter ( n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured. Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries ( P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)D, vitamin D binding protein and albumin-adjusted calcium (Ca) explained 79 % of variance in 25(OH)D half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Ca, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %. Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism. [ABSTRACT FROM AUTHOR]

Summary: Ethnic differences in renal calcium and phosphate excretion exist, which may depend on differences in their dietary intakes and regulatory factors. We report highly significant differences in urinary calcium and phosphate excretion between white British and Gambian adults after statistical adjustment for mineral intakes, indicating an independent effect of ethnicity. Introduction: Populations vary in their risk of age-related osteoporosis. There are racial or ethnic differences in the metabolism of the bone-forming minerals calcium (Ca) and phosphate (P), with a lower renal Ca and P excretion in African-Americans compared to white counterparts, even at similar intakes and rates of absorption. Also, Africans in The Gambia have a lower Ca excretion compared to white British subjects, groups known to differ in their dietary Ca intake. Here, we report on differences in urinary Ca and P excretion between Gambian and white British adults while allowing for known predictors, including dietary intakes. Methods: Participants were healthy white British ( n = 60) and Gambian ( n = 61) men and women aged 60-75 years. Fasting blood and 2-h urine samples were collected. Markers of Ca and P metabolism were analysed. Dietary intake was assessed with country-specific methods. Results: White British older adults had higher creatinine-corrected urinary Ca and P excretion (uCa/uCr, uP/uCr) and lower tubular maximum of Ca and P compared to Gambian counterparts. The predictors of urinary Ca and P differed between groups. Multiple regression analysis showed that dietary Ca and Ca/P were predictors of uCa/uCr and uP/uCr, respectively. Ethnicity remained a significant predictor of uCa/uCr and uP/uCr after adjustment for diet and other factors. Conclusions: Gambian older adults have higher renal Ca conservation than British counterparts. Dietary mineral intakes were predictors of the differences in urinary Ca and P excretion, but ethnicity remained a highly significant predictor after statistical adjustment. This suggests that ethnicity has an independent effect on renal Ca and P handling. [ABSTRACT FROM AUTHOR]

Summary: Fractures due to osteoporosis are common in older people. This study assessed the management of osteoporosis in a group of 85-year-olds and found both assessment and current treatment to be suboptimal. Introduction: Fragility fractures are a major cause of excess mortality, substantial morbidity, and health and social service expenditure in older people. However, much less is known about fracture risk and its management in the very old, despite this being the fastest growing age group of our population. Methods: Cross-sectional analysis of people who reached the age of 85 during the year of 2006 was carried out. Data were gathered by general practice record review (GPRR) and a multidimensional health assessment (MDHA). Results: Seven hundred thirty-nine individuals were recruited. Mean age was 85.55 years (SD 0.44), and 60.2 % were female; 33.7 % ( n = 249) had experienced one or more fragility fractures (F 45.2 % vs M 16.3 % p < 0.001); in total, 332 fractures occurred in these 249 individuals. A formal documented diagnosis of osteoporosis occurred in 12.4 %, and 38 % of individuals had experienced a fall in the last 12 months. When the fracture risk assessment tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidelines were applied, osteoporosis treatment would be recommended in 35.0 %, with a further 26.1 % identified as needing bone mineral density (BMD) measurement and 38.9 % not requiring treatment or BMD assessment. Women were more likely than men to need treatment (47.4 vs 16.3 %, p < 0.001, odds ratio (OR) 4.62 (3.22-5.63)) and measurement of BMD (40.0 vs 5.1 %, p < 0.001, OR 12.4 (7.13-21.6)). Of the 259 individuals identified as requiring treatment, only 74 (28.6 %) were on adequate osteoporosis treatment. Conclusion: The prevalence of high fracture risk in the very old is much higher than the documented diagnosis of osteoporosis or the use of adequate treatments. [ABSTRACT FROM AUTHOR]

Summary: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4 % of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5 % after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture. Introduction: Hip fractures are associated with subsequent fractures, particularly in the year following initial fracture. Age-adjusted hip fracture rates have stabilised in many developed countries, but secular trends in subsequent fracture remain poorly documented. We thus evaluated secular trends (2000-2010) and determinants for the risk of a subsequent major (humerus, vertebral, or forearm) and any (non-hip) fracture after hip fracture. Methods: Patients ≥50 years with a hip fracture between 2000 and 2010 were extracted from the UK Clinical Practice Research Datalink ( n = 30,516). Incidence rates, cumulative incidence probabilities, and adjusted hazard ratios (aHRs) were calculated. Results: Within 1 year following hip fracture, 2.7 and 8.4 % of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5 % after 5 years, respectively. The most important risk factors for a subsequent major fracture within 1 year were the female gender [aHR 1.90, 95 % confidence interval (CI) 1.51-2.40] and a history of secondary osteoporosis (aHR 1.54, 95 % CI 1.17-2.02). The annual risk increased during the study period for both subsequent major (2009-2010 vs. 2000-2002: aHR 1.44, 95 % CI 1.12-1.83) and any (non-hip) facture (2009-2010 vs. 2000-2002: aHR 1.80, 95 % CI 1.58-2.06). Conclusion: The risk of sustaining a major or any (non-hip) fracture after hip fracture is small in the first year. However, given the recent rise in secondary fracture rates and the substantial risk of subsequent fracture in the longer term, fracture prevention is clearly indicated for patients who have sustained a hip fracture. [ABSTRACT FROM AUTHOR]