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High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions. These guidelines have been reviewed and endorsed by the Committee of Scientific Advisors of the International Osteoporosis Foundation, the American Society for Bone and Mineral Research, and the European Calcified Tissue Society

Purpose of Review: Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. Recent Findings: Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium–glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. Summary: New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.

BACKGROUND: Computed tomography (CT), magnetic resonance imaging, and bone scintigraphy are second-line imaging techniques that are frequently used for the evaluation of patients with a clinically suspected scaphoid fracture. However, as a result of varying diagnostic performance results, no true reference standard exists for scaphoid fracture diagnosis. We hypothesized that the use of high-resolution peripheral quantitative CT (HR-pQCT) in patients with a clinically suspected scaphoid fracture could improve scaphoid fracture detection compared with conventional CT in the clinical setting.METHODS: The present study included 91 consecutive patients (≥18 years of age) who presented to the emergency department with a clinically suspected scaphoid fracture between December 2017 and October 2018. All patients were clinically reassessed within 14 days after first presentation, followed by CT and HR-pQCT. If a scaphoid fracture was present, the fracture type was determined according to the Herbert classification system and correlation between CT and HR-pQCT was estimated with use of the Kendall W statistic or coefficient of concordance (W) (the closer to 1, the higher the correlation).RESULTS: The cohort included 45 men and 46 women with a median age of 52 years (interquartile range, 29 to 67 years). HR-pQCT revealed a scaphoid fracture in 24 patients (26%), whereas CT revealed a scaphoid fracture in 15 patients (16%). Patients with a scaphoid fracture were younger and more often male. The correlation between CT and HR-pQCT was high for scaphoid fracture type according to the Herbert classification system (W = 0.793; 95% confidence interval [CI], 0.57 to 0.91; p < 0.001) and very high for scaphoid fracture location (W = 0.955; 95%, CI 0.90 to 0.98; p < 0.001).CONCLUSIONS: In the present study, the number of patients diagnosed with a scaphoid fracture was 60% higher when using HR-pQCT as compared with CT. These findings imply that a substantial proportion of fractures-in this study, more than one-third-will be missed by the current application of CT scanning in patients with a clinically suspected scaphoid fracture.LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

INTRODUCTION: Diagnosing scaphoid fractures remains challenging. High-resolution peripheral quantitative computed tomography (HR-pQCT) might be a potential imaging technique, but no data are available on its feasibility to scan the scaphoid bone in vivo.METHODOLOGY: Patients (≥18 years) with a clinically suspected scaphoid fracture received an HR-pQCT scan of the scaphoid bone (three 10.2-mm stacks, 61-μm voxel size) with their wrist immobilized with a cast. Scan quality assessment and bone contouring were performed using methods originally developed for HR-pQCT scans of radius and tibia. The contouring algorithm was applied on coarse hand-drawn pre-contours of the scaphoid bone, and the resulting contours (AUTO) were manually corrected (sAUTO) when visually deviating from bone margins. Standard morphologic analyses were performed on the AUTO- and sAUTO-contoured bones.RESULTS: Ninety-one patients were scanned. Two out of the first five scans were repeated due to poor scan quality (40%) based on standard quality assessment during scanning, which decreased to three out of the next 86 scans (3.5%) when using an additional thumb cast. Nevertheless, after excluding one scan with an incompletely scanned scaphoid bone, post hoc grading revealed a poor quality in 14.9% of the stacks and 32.9% of the scans in the remaining 85 patients. After excluding two scans with contouring problems due to scan quality, bone indices obtained by AUTO- and sAUTO-contouring were compared in 83 scans. All AUTO-contours were manually corrected, resulting in significant but small differences in densitometric and trabecular indices (CONCLUSIONS: In vivo HR-pQCT scanning of the scaphoid bone is feasible in patients with a clinically suspected scaphoid fracture when using a cast with thumb part. The proportion of poor-quality stacks is similar to radius scans, and AUTO-contouring appears appropriate in good- and poor-quality scans . Thus, HR-pQCT may be promising for diagnosis of and microarchitectural evaluations in suspected scaphoid fractures.

This study aimed to gain insight in specific characteristics and beliefs of FLS non-responders. Introduction The proportion of non-responding fracture liaison service (FLS) invitees is high but characteristics of FLS non-responders are unknown. Methods We contacted FLS non-responders by telephone to consent with home visit (HV) and to fill in a questionnaire or, if HV was refused, to receive a questionnaire by post (Q), to gain insight in beliefs on fracture cause and subsequent fracture risk. Results Out of 716 FLS invitees, 510 attended, nine declined, and 197 did not respond. Of these non-responders, 181 patients were consecutively traced and phoned until 50 consented with HV. Forty-two declined HV but consented with Q. Excluded were eight Q-consenters in whom no choice was offered (either HV or Q) and 81 patients who declined any proposition (non-HV|Q). 62% HV and Q could recall the FLS invitation letter. The fracture cause was differently believed between HV and Q; the fall (96% versus 79%, p = .02), bad physical condition (36% versus 2%, p = .0001), dizziness or imbalance (24% versus Q 7%, p = .03), osteoporosis (16% versus 2%, p = .02), and increased fracture risk (26% versus 17%, NS). Age >= 70, woman, and major fracture were significantly associated with HV consent compared to Q (OR 2.7, 2.5, and 2.4, respectively) and HV compared to non-HV|Q (OR 16.8, 5.3, and 6.1). Conclusion FLS non-responders consider fracture risk as low. Note, 50 patients (about 25%) consented with a home visit after one telephone call, mainly older women with a major fracture. This non-responder subgroup with high subsequent fracture risk is therefore approachable for secondary fracture prevention.

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. Electronic supplementary material The online version of this article (10.1007/s00198-020-05351-x) contains supplementary material, which is available to authorized users.

Improving the clinical outcome of scaphoid fractures may benefit from adequate monitoring of their healing in order to for example identify complications such as scaphoid nonunion at an early stage and to adjust the treatment strategy accordingly. However, quantitative assessment of the healing process is limited with current imaging modalities. In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for the first time to assess the changes in bone density, microarchitecture, and strength during the healing of conservatively-treated scaphoid fractures. Thirteen patients with a scaphoid fracture (all confirmed on HR-pQCT and eleven on CT) received an HR-pQCT scan at baseline and three, six, twelve, and 26 weeks after first presentation at the emergency department. Bone mineral density (BMD) and trabecular microarchitecture of the scaphoid bone were quantified, and failure load (FL) was estimated using micro-finite element analysis. Longitudinal changes were evaluated with linear mixed-effects models. Data of two patients were excluded due to surgical intervention after the twelve-week follow-up visit. In the eleven fully evaluable patients, the fracture line became more apparent at 3 weeks. At 6 weeks, individual trabeculae at the fracture region became more difficult to identify and distinguish from neighboring trabeculae, and this phenomenon concerned a larger region around the fracture line at 12 weeks. Quantitative assessment showed that BMD and FL were significantly lower than baseline at all follow-up visits with the largest change from baseline at 6 weeks (-13.6% and -23.7%, respectively). BMD remained unchanged thereafter, while FL increased. Trabecular thickness decreased significantly from baseline at three (-3.9%), six (-6.7%), and twelve (-4.4%) weeks and trabecular number at six (-4.5%), twelve (-7.3%), and 26 (-7.9%) weeks. Trabecular separation was significantly higher than baseline at six (+13.3%), twelve (+19.7%), and 26 (+16.3%) weeks. To conclude, this explorative HR-pQCT study showed a substantial decrease in scaphoid BMD, Tb.Th, and FL during the first 6 weeks of healing of conservatively-treated scaphoid fractures, followed by stabilization or increase in these parameters. At 26 weeks, BMD, trabecular microarchitecture, and FL were not returned to baseline values. research foundation of VieCuri Medical Center Noord-Limburg, The Netherlands [NL62476.068.17]

Long-term exposure to anti-epileptic drugs has been shown to decrease bone mineral density (BMD). The aim of this 7-year follow-up study was to explore changes in bone status, using quantitative ultrasound (QUS) and Dual-energy X-ray Absorptiometry (DXA) in adults with refractory epilepsy and intellectual disability (ID) residing at a long-term care facility. Both measurements can be challenging to conduct in this population.In 2009 and 2016, a total of 126 patients (18-79 years) underwent QUS of the heel and DXA of lumbar spine (LS) and hip (femoral neck (FN) and total hip (TH)). Subgroup analysis was performed for patients with (group A, n = 53) and without (group B, n = 73) bisphosphonate use during follow-up.Overall, weak to moderate correlations between changes in DXA and QUS parameters were found. For group A, correlations varied from r = .31 to .59, whereas correlations did not exceed r = .40 in group B. Patients in group A showed a larger increase or a smaller decrease in BMD for all DXA regions during follow-up (p .001 for ΔLS and ΔFN BMD, p = .001 for ΔTH BMD). For change in QUS parameters, no significant difference between groups was found.In this study we demonstrated the limited use of QUS in the monitoring of bone status in our study population. Although correlations between changes in QUS parameters and axial DXA are positive and mostly significant, QUS only explains little of the variability in DXA values and is inadequate for measuring treatment response in this population.

Summary This study evaluated the 2-year persistence with teriparatide in the Netherlands. Analyses showed that the risk of non-persistence was 28% lower in patients who were followed according to an additional educational and motivational support program. Introduction Until recently, teriparatide (TPTD) was a third-line treatment option for severe osteoporosis in the Netherlands, which could only be prescribed by medical specialists based on a specific medical statement. We aimed to determine whether an educational and motivational support program (EMSP) increased 2-year treatment persistence with TPTD in patients with severe osteoporosis. Methods We evaluated persistence in 1573 Dutch patients treated with TPTD from January 2013 until January 2018. From January 2013 onwards, all patients received a basic support program (BSP) consisting of an educational home visit to initiate TPTD treatment and phone calls (at 1, 2.5 and 8 weeks). Since May 2015, all patients received the EMSP consisting of the BSP extended with evaluation of medication adherence during phone calls, an additional phone call (at 12 months), and motivational letters at 9 and 14 months. Results The EMSP showed a statistically significantly higher 2-year persistence (78%) with TPTD as compared with the BSP (72%). Reasons for treatment discontinuation were comparable between groups, except for the proportion of patients who had stopped TPTD administration due to side effects, which was significantly lower in the EMSP group (8% vs. 15% in BSP, p

Summary CT scans performed to evaluate chronic obstructive pulmonary disease (COPD) also enable evaluation of bone attenuation (BA; a measure of bone density) and vertebral fractures (VFs). In 1239 current/former smokers with (n = 999) and without (n = 240) COPD, the combination of BA and prevalent VFs was associated with the incident VF risk. Introduction Chest CT scans are increasingly used to evaluate pulmonary diseases, including COPD. COPD patients have increased risk of osteoporosis and VFs. BA on CT scans is correlated with bone mineral density and prevalent VFs. The aim of this study was to evaluate the association between BA and prevalent VFs on chest CT scans, and the risk of incident VFs in current and former smokers with and without COPD. Methods In participants of the ECLIPSE study with baseline and 1-year and 3-year follow-up CT scans, we evaluated BA in vertebrae T4–T12 and prevalent and incident VFs. Results A total of 1239 subjects were included (mean age 61.3 ± 8.0, 61.1% men, 999 (80.6%) COPD patients). The mean BA was 155.6 ± 47.5 Hounsfield Units (HU); 253 (20.5%) had a prevalent VF and 296 (23.9%) sustained an incident VF within 3 years. BA and prevalent VFs were associated with incident VFs within 1 (per − 1SD HR = 1.38 [1.08–1.76] and HR = 3.97 [2.65–5.93] resp.) and 3 years (per − 1SD HR = 1.25 [1.08–1.45] and HR = 3.10 [2.41–3.99] resp.), while age, sex, body mass index (BMI), smoking status and history, or presence of COPD was not. In subjects without prevalent VFs and BA, and for 1-year incidence, BMI values were associated with incident fractures (1 year, BA per − 1SD HR = 1.52 [1.05–2.19], BMI per SD HR = 1.54 [1.13–2.11]; 3 years, per − 1SD HR = 1.37 [1.12–1.68]). Conclusions On CT scans performed for pulmonary evaluation in (former) smokers with and without COPD, the combination of BA and prevalent VFs was strongly associated with the short-term risk of incident VFs. Electronic supplementary material The online version of this article (10.1007/s00198-019-04977-w) contains supplementary material, which is available to authorized users.

Background: Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). Methods: A dual-energy X-ray absorptiometry of lumbar spine (L1–L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. Results: Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > − 2.0). Of the 16 children with a low BMD (Z-score ≤ − 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28–2.50 mmol/L) and (supplemented) vitamin D (16–137 nmol/L) were within the normal range. Conclusions: This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.

Purpose To determine the incidence of clinical fractures over seven years of follow-up, in adults with epilepsy and intellectual disability, residing in a long-stay care facility. Methods In 2009, all institutionalized adult patients (n = 261) were invited to undergo a Dual-energy X-ray Absorptiometry (DXA) measurement and a Vertebral Fracture Assessment (VFA). Participants were followed over seven years or until date of discharge (in case of moving from the care facility) or date of death. The patients’ medical files were screened for radiology reports and staff notes, to identify clinical fractures. Fracture incidence rates (IR) were determined and compared for subgroups, by calculating incidence rate ratios. Hazard ratios were calculated to identify factors associated with fracture risk, using Cox Proportional Hazards analyses. Results A total of 205 patients (124 male, 60.5%) aged between 18 and 88 years (median 48, IQR 34–60) were enrolled. At baseline, 92 patients (44.9%) were diagnosed with osteopenia and 65 (31.7%) with osteoporosis. Between 2009 and 2016, 30 patients (14.6%) deceased and 3 patients (1.5%) left the care facility. During follow-up, 156 clinical fractures were reported in 82 patients (40.0%). Thirty-eight patients (18.5%) had at least one major osteoporotic fracture. Overall, the IR was 11.6 fractures per 100 person-years. Fracture risk was significantly lower in patients who were wheelchair dependent than in patients who were able to walk (p Conclusion This study demonstrated that 40% of institutionalized adults with epilepsy and intellectual disability had at least one clinical fracture during seven years of follow-up, despite adequate anti-osteoporosis treatment.

Telephone call intervention did not improve alendronate persistence in Fracture Liaison Service (FLS) patients in this study. A bone turnover marker cut-off point for alendronate persistence is proposed for individual FLS patients.FLS aims to prevent subsequent fractures, which should include improving patients' persistence with prescribed oral bisphosphonates. We studied the influence of telephone calls and the predictive value of changes in bone turnover markers (BTMs) for evaluating persistence with alendronate.Postmenopausal women with a recent fracture and osteoporosis who started alendronate were randomized to receive three phone calls (PC) (after 1, 4, and 12 months) or no phone calls (no PC). s-CTX and P1NP were measured at baseline and after 3, 6, 9, and 12 months. As a reference group, 30 postmenopausal osteopenic patients with a recent fracture were analyzed as well. Persistence was assessed using the Dutch National Switch Point Pharmacies-GPs database and cross-referenced with PC, no PC, and BTM changes. Cut-off values of BTMs were calculated based on least significant change (LSC) and also on underrunning median values of the untreated osteopenic postmenopausal reference group with a recent fracture.Out of 119 patients, 93 (78%) completed 12 months follow-up (45 PC and 48 no PC). Mean age was 69 years. Persistence was similar in PC and no PC participants. The cut-off value > 29% ( 36% (In this context, telephone calls did not improve persistence. In around 90% of patients, 1-year alendronate persistence was confirmed by achieving LSC of s-CTX and of P1NP at 12 months.

Fracture risk in patients with type 2 diabetes mellitus (T2DM) is increased, and the mechanism is multifactorial. Recent research on T2DM-induced bone fragility shows that bone mineral density (BMD) is often normal or even slightly elevated. However, bone turnover may be decreased and bone material and microstructural properties are altered, especially when microvascular complications are present. Besides bone fragility, extra-skeletal factors leading to an increased propensity to experience falls may also contribute to the increased fracture risk in T2DM, such as peripheral neuropathy, retinopathy and diabetes medication (e.g. insulin use). One of the probable additional contributing factors to the increased fall and fracture risks in T2DM is sarcopenia, the age related decline in skeletal muscle mass, quality and function. Although the association between sarcopenia, fall risk, and fracture risk has been studied in the general population, few studies have examined the association between T2DM and muscle tissue and the risks of falls and fractures. This narrative review provides an overview of the literature regarding the multifactorial mechanisms leading to increased fracture risk in patients with T2DM, with a focus on sarcopenia and falls.

Summary X-ray, CT and DXA enable diagnosis of vertebral deformities. For this study, level of agreement of vertebral deformity diagnosis was analysed. We showed that especially on subject level, these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients. Introduction X-ray and CT are frequently used for pulmonary evaluation in patients with chronic obstructive pulmonary disease (COPD) and also enable to diagnose vertebral deformities together with dual-energy X-ray absorptiometry (DXA) imaging. The aim of this research was to study the level of agreement of these imaging modalities for diagnosis of vertebral deformities from T4 to L1. Methods Eighty-seven subjects (mean age of 65; 50 males; 57 COPD patients) who had X-ray, chest CT (CCT) and DXA were included. Evaluable vertebrae were scored twice using SpineAnalyzer™ software. ICCs and kappas were calculated to examine intra-observer variability. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUROC) were calculated to compare vertebral deformities diagnosed on the different imaging modalities. Results ICCs for height measurements were excellent (> 0.94). Kappas were good to excellent (0.64–0.77). At vertebral level, the AUROC was 0.85 for CCT vs. X-ray, 0.74 for DXA vs. X-ray and 0.77 for DXA vs. CCT. Sensitivity (51%–73%) and PPV (57%–70%) were fair to good; specificity and NPV were excellent (≥ 96%). At subject level, the AUROC values were comparable. Conclusions Reproducibility of height measurements of vertebrae is excellent with all three imaging modalities. On subject level, diagnostic performance of CT (PPV 79–82%; NPV 90–93%), and to a slightly lesser extend of DXA (PPV 73–77%; NPV 80–89%), indicates that these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients. Electronic supplementary material The online version of this article (10.1007/s00198-018-4412-1) contains supplementary material, which is available to authorized users.

Summary The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. Introduction This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. Methods The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. Results The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥ 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. Conclusions The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.

Background Painful diabetic neuropathy (PDN) is known to negatively affect psychosocial functioning as expressed by enhanced levels of anxiety and depression. The aim of this study was to specify diabetes and pain-related fears. Methods This questionnaire-based cross-sectional study included 154 patients with PDN (mean age 65.7 ± 6.6 years). Correlation analyses corrected for age, gender, pain intensity, pain duration and insulin treatment were performed to assess the associations of fear of hypoglycaemia (Hypoglycaemia Fear Survey, HFS), kinesiophobia (Tampa Scale of Kinesiophobia, TSK), fear of pain (Pain Anxiety Symptom Scale, PASS-20), fear of falling (Falls Efficacy Scale-I, FES-I), fear of fatigue (Tampa Scale of Fatigue, TSF) and fear of negative evaluation (Brief Fear of Negative Evaluation Scale, BFNE), with quality of life (QoL) (Norfolk Quality of Life Questionnaire, Diabetic Neuropathy Version, QOL-DN) and disability (Pain Disability Index, PDI), respectively. Results In univariate analyses, all fears were independently associated with QOL-DN and PDI (p

The Summary We evaluated the impact of a new Dutch guideline on systematic implementation of densitometric Vertebral Fracture Assessment (VFA) in patients with a recent nonvertebral fracture. Systematic implementation resulted in a significant increase of VFA, diagnosis of vertebral fractures (VFs), and percentage of patients eligible for treatment. Introduction VFs are underdiagnosed although they are important predictors of fracture risk, independent of age and bone mineral density (BMD). The Dutch guideline on osteoporosis and fracture prevention recommends VFA in all patients aged > 50 years with a recent non-VF. Our aim was to evaluate the effect of systematic implementation of densitometric VFA in patients with a recent non-VF at the fracture liaison service (FLS). Methods VFA was performed on lateral images of the spine using dual-energy X-ray absorptiometry (DXA) and graded according to Genant using Spine Analyzer software. Results We evaluated 582 patients before and 484 after implementation (mean age 67 and 66 years; 71 and 74% women, respectively). Performing VFA increased from 4.6 to 97.1% (p < 0.001) and the diagnosis of VFs from 2.2 to 26.2% for grade >= 1 (p < 0.001) and from 0.9 to 14.7% for grade >= 2 (p < 0.001). Prevalence of VFs increased with age (5.2% in 50-59-year olds to 27.8% in 80+-year olds, p < 0.001), but was similar for both genders, non-VF locations, and BMD. Including patients with osteopenia and a VF increased the percentage of patients eligible for treatment by a quarter, from 31.0% in the pre-guideline to 38.4% in the post-guideline cohort. Conclusions Systematic guideline implementation resulted in a significant increase of VFA, diagnosis of VFs, and percentage of patients eligible for treatment. VFA contributes to documenting the high prevalence of VFs in patients visiting the FLS with a non-VF in both genders, at any age, non-VF location, and BMD. the research for this article was partly funded by the Eli Lilly Company, under grant number: VFA, B3D-UT-0029. The funding source had no role in this manuscript.

This study revealed the risk of major osteoporotic fracture in patients with sarcoidosis exposed to glucocorticoids. Current use of glucocorticoids was associated with a risk of fracture, with no difference between patients with and without sarcoidosis. Sarcoidosis per se was not associated with an increased fracture risk.Introduction Sarcoidosis is a multi-organ, chronic inflammatory, granulomatous disorder that most frequently affects the lungs, lymph nodes, skin, eyes, and liver, but may occur in any organ, including the bones. While oral glucocorticoids (GCs) are commonly used as initial treatment, little is known about the risk of major osteoporotic fractures in patients with sarcoidosis exposed to GCs.Methods A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1995 and December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) of major osteoporotic fractures in subjects with and without sarcoidosis stratified by average daily and cumulative dose exposures.Results A total of 376,858 subjects with a major osteoporotic fracture and the same number of subjects without this event were identified (mean age 64.2 +/- 19.5 years, 69% female). In patients with sarcoidosis (n = 124), current use of GC was associated with an increased risk of major osteoporotic fracture (adjusted (adj.) OR 1.74; 95% CI 1.17-2.58), which dropped to baseline levels after discontinuation. In subjects without sarcoidosis, this risk was comparable (adj. OR 1.36; 95% CI 1.32-1.40). In sarcoidosis patients, cumulative dose 1.0-4.9 g and > 10 g prednisolone equivalents were associated with increased risk of major osteoporotic fracture (adj. OR 2.75; 95% CI 1.06-7.14 and 2.22; 95% CI 1.17-4.22, respectively), whereas a cumulative dose of

Summary The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. Introduction The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. Methods MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. Results Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (−0.04 for the EQ-5D utility score, −5.07 for the EQ-5D visual analog scale, −3.35 for OPAQ physical function, −4.60 for OPAQ emotional status, and −8.50 for OPAQ back pain; P ≤ 0.001 for all values). Decrements in month 12 treatment satisfaction scores were −6.46 for patients with baseline GI events and −7.88 for patients with post-baseline GI events. Conclusions The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. Electronic supplementary material The online version of this article (doi:10.1007/s00198-017-4116-y) contains supplementary material, which is available to authorized users.

Identifying determinants of long-term functional outcome after a distal radius fracture is challenging. Previously, we reported on the association between early HR-pQCT measurements and clinical outcome 12 weeks after a conservatively treated distal radius fracture. We extended the follow-up and assessed functional outcome after two years in relation to early HR-pQCT derived bone parameters.HR-pQCT scans of the fracture region were performed in 15 postmenopausal women with a distal radius fracture at 1-2 (baseline), 3-4 weeks and 26 months post-fracture. Additionally, the contralateral distal radius was scanned at baseline. Bone density, micro-architecture parameters and bone stiffness using micro-finite element analysis (FEA) were evaluated. During all visits, wrist pain and function were assessed using the patient-rated wrist evaluation questionnaire (PRWE), quantifying functional outcome with a score between 0 and 100.Two-year PRWE was associated with torsional and bending stiffness 3-4 weeks post-fracture (R-2: 0.49, p = 0.006 and R-2: 0.54, p = 0.003, respectively). In contrast, early micro-architecture parameters of the fracture region or contralateral bone parameters did not show any association with long-term outcome.This exploratory study indicates that HR-pQCT with mu FEA performed within four weeks after a distal radius fracture captures biomechanical fracture characteristics that are associated with long-term functional outcome and therefore could be a valuable early outcome measure in clinical trials and clinical practice.

A Summary This questionnaire-based study evaluated the reasons for attendance or non-attendance at the fracture liaison service in patients with a recent fracture. Frailty, male sex, living alone, and low education were associated with non-attendance, and the information perceived by the patient was associated with attendance.Introduction The purpose of this study was to evaluate hospital registration- and patient-related factors associated with attendance or non-attendance to the Fracture Liaison Service (FLS).Methods Out of 1728 consecutive patients registered with a recent fracture at hospital entry, and after exclusion of 440 patients because of death, residence in a nursing home, already on osteoporosis treatment, or recent DXA, 1288 received an FLS invitation. We evaluated the hospital registration of fractures at entry and exit of the hospital. A questionnaire was sent to all invited patients to evaluate factors related to non-attendance (including age, gender, frailty, living alone, income, education, extrinsic motivations (impact of perceived information) and intrinsic motivations (patient's own perceived views and opinions) and to attendance (personal impact of clinical professionals' advice).Results There were 278 more hospital exit codes than entry codes. Of the 1288 invited patients, 745 returned analyzable questionnaires (537 attenders and 208 non-attenders). Non-attendance was associated with male gender (OR: 2.08, 95% CI: 1.35, 3.21), frailty (OR: 1.62, CI: 1.08, 2.45), living alone (OR:2.05, CI: 1.48, 2.85), low education (OR: 1.82, CI: 1.27, 2.63), not interested in bone strength (OR: 1.85, CI: 1.33, 2.63), and being unaware of increased subsequent fracture risk (OR: 1.75, CI: 1.08, 2.86). Information perceived by the patient was significantly associated with attendance (OR: 3.32, CI: 1.75, 6.27).Conclusion Fracture entry registration inaccuracies, male gender, frailty, living alone, having low general education, or low interest in bone health and subsequent fracture risk were independently associated with FLS non-attendance. Adequately perceived advice (to have a bone densitometry and attend the FLS) was strongly associated with FLS attendance.

ObjectivesThe purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS).MethodsThirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated.ResultsAt baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (-4.4 versus -1.1 mgHA/cm(3), respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively).ConclusionsHR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs. The study is supported by unrestricted grants from the Weijerhorst foundation (WH-2) and Pfizer (WS2056904).

In the first year, after an osteoporotic fracture of a hip, forearm, upper arm, or spine, the dispensing rates of antidepressants and benzodiazepines increased significantly. After those fractures, recent and past use of antidepressants and benzodiazepines was associated with increased all-cause mortality; current use was not associated with mortality risk.INTRODUCTION: It remains unclear to what extent use of antidepressants and benzodiazepines is associated with mortality risk after a major osteoporotic fracture (MOF). We aimed to study the cumulative use of antidepressants and benzodiazepines during the year after MOF or hip fracture (HF) and whether the use was associated with mortality.METHODS: A cohort study was performed within the Dutch PHARMO Database Network including all patients aged 65+ with a first record of MOF (hip, humerus, forearm, and clinical vertebral fracture) between 2002 and 2011. Data were analyzed using Cox regression models, adjusted for comorbidities, and concomitant medication use and broken down to index fracture type.RESULTS: A total of 4854 patients sustained a first MOF, of whom 1766 patients sustained a HF. Mean follow-up was 4.6 years, divided in 30-day periods. The cumulative antidepressant and benzodiazepine use during the first year after MOF increased from 10.6 to 14.7% and from 24.0 to 31.4%, respectively. Recent (31-92 days before each follow-up period) and past use (> 92 days before) of antidepressants and benzodiazepines after MOF or HF was associated with an increased all-cause mortality risk but current use (CONCLUSION: There is a considerable increase in dispensing rate of antidepressants and benzodiazepines in the first year after a MOF. Recent and past use of these medications was associated with all-cause mortality. The finding that current use was not associated with mortality should be further explored and may probably be explained by the healthy survivor's bias.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean +/- sd 0.33 +/- 0.63 vs 0.38 +/- 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH >= 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (beta 0.47, 95% CI 0.4-0.6, p < 0.01 and beta 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated. This study was funded by an unrestricted grant from Pfizer and the Weijerhorst Foundation.

SummaryWe studied the incidence of subsequent fractures in persons of 50+ years from 1990 to 2012 and the relative risk (RR) of subsequent fractures after an index femur/hip fracture, stratified per 5-year age band. Patients suffering a fracture have a high incidence of a subsequent fracture; the RR of subsequent fracture after a femur/hip fracture ranged from 2 to 7.IntroductionRecent information on the risk of subsequent fractures after a broad range of index fractures in the UK population is scarce. We therefore studied the rates of subsequent fractures of the femur/hip, humerus, radius/ulna, vertebrae, rib, or pelvis after fractures at one of these sites from 1990 to 2012 in 3,156,347 UK men and women aged 50 years or over.MethodsWe undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD). The incidence of subsequent fractures at a specific site was calculated by dividing the observed number of fractures by the number of person-years (py) at risk. The relative risk (RR) of subsequent fractures after a femur/hip fracture, by 5-year age band, was calculated by dividing the incidence of a specific subsequent fracture type by the incidence of first fractures at the same site in the same age group.ResultsThe highest subsequent fracture incidence after a femur/hip fracture was for humerus fracture in men (59.5/10.000 py) and radius/ulna fracture in women (117.2/10.000 py). After an index fracture of the radius/ulna, humerus fracture in men (59.3/10.000 py) and femur/hip fracture in women (82.4 per 10.000 py) were most frequent. The RR of fractures after a femur/hip fracture ranged from 2 to 7 and were highest in men and younger age groups.ConclusionPatients suffering a fracture have a high incidence of a subsequent fracture. Our findings demonstrate the importance of fracture prevention in patients with a history of a fracture by adequate medical diagnosis and treatment.

© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48–0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66–1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031–0.70)] for n-BP vs. etidronate]. Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Background: We developed a semi-automated algorithm that detects cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), and extended it with trabecular void volume measurement In this study we tested the reproducibility of the algorithm using scan/re-scan data. Methods: Second and third metacarpophalangeal joints of 21 subjects (mean age 49 (SD 11) years, 17 early rheumatoid arthritis and 4 undifferentiated arthritis, all diagnosed < 1 year ago) were imaged twice by HR-pQCT on the same day with repositioning between scans. The images were analyzed twice by one operator (OP1) and once by an additional operator (OP2), who independently corrected the bone contours when necessary. The number, surface and volume of interruptions per joint were obtained. Intra- and inter-operator reliability and intra-operator reproducibility were determined by intra-class correlation coefficients (ICC). Intra-operator reproducibility errors were determined as the least significant change (LSCSD). Results: Per joint, the mean number of interruptions was 3.1 (SD 3.6), mean interruption surface 4.2 (SD 7.2) mm(2), and mean interruption volume 3.5 (SD 10.6) mm(3) for OP1. Intra- and inter-operator reliability was excellent for the cortical interruption parameters (ICC >= 0.91), except good for the inter-operator reliability of the interruption surface (ICC >= 0.70). The LSCSD per joint was 4.2 for the number of interruptions, 5.8 mm(2) for interruption surface, and 3. 2 mm(3) for interruption volume. Conclusions: The algorithm was highly reproducible in the detection of cortical interruptions and their volume. Based on the LSC findings, the potential value of this algorithm for monitoring structural damage in the joints in early arthritis patients needs to be tested in clinical studies. The study is supported by unrestricted grants from the Weijerhorst foundation (WH-2) and Pfizer (WS2056904). The funders had no role in the design of the study, the collection, analysis and interpretation of the data, and in writing the manuscript.

Summary In this cross-sectional study, two-thirds of Fracture Liaison Service (FLS) patients had comorbidities and medications associated with increased bone- or fall-related fracture risk. Bone-related and fall-related fracture risk (BRR and FRR) were associated with age and fracture type, but not with gender or BMD. Systematic evaluation of these factors leads to a more profound assessment in FLS care. Introduction This study is a systematic evaluation of comorbidities and medications associated with increased fracture risk in patients aged 50–90 years with a recent fracture visiting the FLS. Methods In this cross-sectional cohort study, comorbidities were classified according to ICD-10 and medications according to the Anatomic Therapeutic Chemical (ATC) classification and further categorized into those associated BRR and FRR. Results Of 1282 patients (72% women; 65 ± 9 years), 53% had at least one BRR, 46% had at least one FRR, and 66% at least one BRR and/or FRR. At least one BRR, as well as at least one FRR were associated with age, BMI, and fracture type, but not with gender or BMD. The proportion of patients with only BRR (± 20%) or only FRR (± 10%) was similar among ages, gender, BMI, fracture type, and BMD. The combination of at least one BRR and at least one FRR was significantly associated with age, BMI, and major fractures, but not with gender or BMD. Conclusion Comorbidities and medications associated with increased fracture risk are present in two-thirds of patients visiting the FLS. In addition, the proportion of patients having a combination of BRR and FRR increased significantly with age, BMI, and fracture severity. This indicates that systematic evaluation of these factors is important for a more profound assessment of subsequent fracture risk in FLS care. Electronic supplementary material The online version of this article (10.1007/s00198-017-4290-y) contains supplementary material, which is available to authorized users.

Summary In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. Introduction To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. Methods Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. Results After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. Conclusions In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM. Electronic supplementary material The online version of this article (10.1007/s00198-018-4678-3) contains supplementary material, which is available to authorized users.

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Introduction Although the effect of hormonal therapy (HT) on fracture risk during treatment of breast cancer is established, information about fracture incidence after completion of HT is scarce. In this hospital based observational study we evaluated fracture rates after completion of HT in pre- and postmenopausal women with breast cancer. Methods All women diagnosed with breast cancer in the VieCuri Medical Center between 1998 and 2005 who started adjuvant HT with aromatase inhibitors or tamoxifen were included (n = 289). Data on fracture rate, fracture type and risk factors for fracture after completion of HT were collected. Results The overall fracture rate was 12% in pre- and 15% in postmenopausal women respectively during an average follow-up of 3.1 ± 2.9 years. The number of patients with at least one fracture was 41 (14%). There was no difference in fracture rates between different types of HT (P = 0.15). The most common types of fractures were toe/finger fractures in premenopausal- and hip and major fractures in postmenopausal women. Median time to first fracture was shorter in premenopausal women (1.4 years, IQR 0.2–3.5) than in postmenopausal women (2.4 years, IQR 0.7–5.1, P = 0.01). A history of previous fracture was a significant risk factor for fracture in postmenopausal women (HR 3.9, 95% CI 1.3–11.7). Conclusion Fracture rates in the first years after cessation of HT for breast cancer were 12% and 15% for pre- and postmenopausal women respectively. The most common fractures in postmenopausal women were hip and major fractures.

Background: Sedentary behaviour (SB) is a potential risk factor for suboptimal bone deposition in youth. Results: Total SB was negatively associated with lower extremity bone outcomes, while no association was observed with total body bone outcomes. Insufficient evidence was found for an association between total SB and lumbar spine bone outcomes. Conclusion: This review highlights the heterogeneity of the available evidence and emphasizes the need for well-designed studies. Electronic supplementary material The online version of this article (10.1007/s00198-017-4195-9) contains supplementary material, which is available to authorized users.

Objectives To introduce a fully-automated algorithm for the detection of small cortical interruptions (>= 0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully-and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully-and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully-and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully-vs. semi-automated procedure (respectively, 8.6mm(2) vs. 5.8mm(2) and 6.1mm(2), p = 0.01). Reliability was almost perfect between the fully-and semi-automated procedure for both the number and surface of interruptions (ICC >= 0.95) and the proportion of matching interruptions was high (>= 76%). Also the inter-operator reliability was almost perfect (ICC >= 0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. This work was supported by: Weijerhorst Foundation (JvdB), http//www.deweijerhorst.nl/ weijerhorst/home. funding that was used to purchase the HR-pQCT scanner and pay half of the PhD student salaries of MP and AS. It was also supported by Pfizer (PG), grant number: WS2056904, http//www.pfizer.nl/. This funding was used to perform our study (NL42300.068.12 / METC 12-2-037) of HR-pQCT imaging in patients with RA compared to conventional imaging techniques.

People detained in prisons and other closed settings are at elevated risk of infection with hepatitis C virus (HCV). We undertook a systematic review and meta-analysis with the aim of determining the rate of incident HCV infection and the prevalence of anti-HCV among detainees in closed settings. We systematically searched databases of peer-reviewed literature and widely distributed a call for unpublished data. We calculated summary estimates of incidence and prevalence among general population detainees and detainees with a history of injection drug use (IDU), and explored heterogeneity through stratification and meta-regression. The summary prevalence estimates were used to estimate the number of anti-HCV positive prisoners globally. HCV incidence among general detainees was 1.4 per 100 person-years (py; 95% confidence interval [CI]: 0.1, 2.7; k = 4), and 16.4 per 100 py (95% CI: 0.8, 32.1; k = 3) among detainees with a history of IDU. The summary prevalence estimate of anti-HCV in general detainees was 26% (95% CI: 23%, 29%; k = 93), and in detainees with a history of IDU, 64% (95% CI: 58%, 70%; k = 51). The regions of highest prevalence were Central Asia (38%; 95% CI 32%, 43%; k = 1) and Australasia (35%; 95% CI: 28%, 43%; k = 9). We estimate that 2.2 million (range: 1.4-2.9 million) detainees globally are anti-HCV positive, with the largest populations in North America (668,500; range: 553,500-784,000) and East and Southeast Asia (638,000; range: 332,000-970,000). Conclusion: HCV is a significant concern in detained populations, with one in four detainees anti-HCV-positive. Epidemiological data on the extent of HCV infection in detained populations is lacking in many countries. Greater attention towards prevention, diagnosis, and treatment of HCV infection among detained populations is urgently required. (Hepatology 2013;58:1215–1224)

Introduction: Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs (AOD). Methods: We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50 years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000 person-years (py).Results: In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 23 to 169.7 per 10,000 py), followed by a plateau and a 12% decrease in the last three years. In men, a less steep increase from 1990 to 2007 (from 1.4 to 45.3 per 10,000 py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85-89 years (248.9 per 10,000 py in women. and 1193 in men). There were marked differences between ethnic groups and regions. Bisphosphonates were the most frequently prescribed AODs: etidronate till 2000, and then subsequently alendronate.Conclusion: We have demonstrated marked secular changes in rates of anti-osteoporosis drug prescription over the last two decades. The plateau (and decrease amongst women) in rates in recent years, set against an ever ageing population, is worrying, suggesting that the well-documented care gap in osteoporosis treatment persists. The differences in prescription rates by geographic location and ethnicity raise intriguing questions in relation to underlying fracture rates, provision of care and health behaviour.Summary: We studied the prescription incidence of anti-osteoporosis drugs (AOD) from 1990 to 2012 in the UK CPRD. Overall AOD prescription incidence showed a strong increase from 1990 to 2006, followed by a plateau in both sexes and a decrease amongst women in the last three years. (C) 2016 Elsevier Inc. All rights reserved.

Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in reexposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-.-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17-25% of the VZV re-exposed grandparents and for less than one year. This work was supported by grants of the Research Foundation Flanders (predoctoral fellowship to B.O.; postdoctoral fellowship to E.L.; project grants G.0409.12N and G.0903.13N); the Hercules Foundation-Belgium and the University of Antwerp (Concerted Research Action; predoctoral fellowships to J.V.D.B. and A.V.; Methusalem funding).

Sedentary behaviour (SB) is increasing in Western societies and some studies suggest a deleterious effect of SB on bone. The aim of this systematic review was to examine the association between SB and bone health in children, adolescents and young adults. Electronic databases (PubMed, MEDLINE, PsycINFO and Science Citation Index) were searched for relevant articles up to January 9, 2017. Studies were included when results on bone health (e.g. strength, mass and structure) and either subjectively (questionnaires) or objectively (accelerometry) measured SB were reported in healthy participants ≤24 years. Two reviewers independently screened titles and abstracts for eligibility, rated methodological quality and extracted data. Seventeen observational studies were included. Several studies that used DXA or quantitative ultrasound suggested that objectively measured SB was negatively associated with lower extremity bone outcomes, such as femoral neck bone mineral density. The magnitude of this negative association was small and independent of moderate-to-vigorous physical activity. In contrast to the lower extremities, there was insufficient evidence for an association of lumbar spine bone outcomes with objectively measured SB. In high-quality studies that used DXA, no association was observed between objectively measured SB and total body bone outcomes. In studies using questionnaires, none of these relationships were observed. Well-designed longitudinal studies, objectively measuring SB, are needed to further unravel the effect of SB, physical activity and their interaction on bone health. Electronic supplementary material The online version of this article (doi:10.1007/s00198-017-4076-2) contains supplementary material, which is available to authorized users.

In this cohort of relatively young and well-treated participants with type 2 diabetes, we found no association between diabetes status and a history of previous fractures and recent falls. Furthermore, no association between diabetes severity and previous fractures or recent falls was found. Introduction In this study, we examined the association between glucose metabolism status and historical fractures or recent falls and the effect of diabetes severity (glucose control, insulin use, and diabetes duration) on falls and fractures in the participants with type 2 diabetes. Methods Cross-sectional data from 2005 participants of the Maastricht Study. Falls in the past 6 months and fractures >= age 50 were assessed by questionnaire. Glucose metabolism status (normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes) was based on the oral glucose tolerance test and medication use. Results In the completely adjusted model, the odds for a fall were not significantly higher in those with impaired glucose metabolism status (OR (95% CI) 1.28 (0.93-1.77)) or with type 2 diabetes (OR (95% CI) 1.21 (0.80-1.81)) compared with the group with normal glucose metabolism. Within the group with type 2 diabetes, there were no significant differences with regard to reported falls between participants with HbA1c >7 % (53 mmol/mol) versus HbA1c 5 versus

Contains fulltext : 57373.pdf (Publisher’s version ) (Closed access) The purpose of this study was to examine the uptake and metabolism of 5-fluorouracil (5-FU) in human liver metastases. Patients with liver metastases of colorectal cancer were treated with 5-FU (500/600 mg/m)+folinic acid with or without trimetrexate. The clinical application of F-magnetic resonance spectroscopy (MRS) of 5-FU in a random group of patients (n=17) was investigated. MR spectra of all patients showed 5-FU and catabolite resonances, and fluoronucleotides were also seen in seven patients. A correlation was found between maximum levels of 5-FU catabolites as measured by F-MRS and response in a group with larger metastases. However, such correlation was not observed in a group with smaller metastases, probably because of a significant contribution of normal liver tissue to the MR spectra.

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (a parts per thousand yen1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study. A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate). In two previous multicenter, open-label studies, postmenopausal women a parts per thousand yen55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed. In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups. Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

Item does not contain fulltext Klinefelter's syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only few bone mineral density (BMD) and no quantitative ultrasound (QUS) data are available in these patients after long-term testosterone replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 12.4 years (mean SD). Patients had been treated with oral or parenteral androgens for 9.2 8.2 years (range 1-32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS patient group were compared. Overall, based on the three reference databases, 46% and 63% of the KS patients had a T-score between -1 and -2.5 and a further 10% and 14% had a T-score < or = -2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS patients had a T-score between -2.5 and -1, while 2% had a T-score < or = -2.5 for BUA and/or SOS. BUA (77.7 15.0 dB/MHz) and SOS (1518.8 36.5 m/s) were significantly lower in the KS patients than in age- and height-matched controls (87.1 17.8 dB/MHz, p < 0.005, and 1536.5 42.5 m/s, p < 0.05). Correlation coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or BMAD T-score < or = -2.5 with either BUA or SOS was not statistically significant. Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS parameters were determined no BMD measurements were performed, we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score < -1 or even < or = -2.5, based on different North American reference databases. This percentage was even higher for BMAD. QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be used to predict BMD or BMAD in KS patients.

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

Background Early detection of bone erosions in rheumatoid arthritis (RA) is essential for initiating or intensifying treatment and improving outcome. To date, conventional radiography (CR) is considered the gold standard to detect joint damage. Magnetic resonance imaging (MRI) has shown to be superior over CR with respect to detecting erosions, and also visualizes the inflammation itself, but may not be feasible in daily practice. High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), a novel imaging technique, allows three dimensional analysis of cortical and trabecular bone structure in finger joints at a micro level. Previous research showed that HR-pQCT is able to detect more erosions than CR[1]. Objectives First, to cross-sectionally compare the number of erosions detected by HR-pQCT with erosions detected on CR and MRI, in second and third MCP and PIP joints of patients with RA and healthy controls (HC). Secondly, to compare erosions scored by HR-pQCT with erosions, synovitis and bone marrow edema (BME) on MRI images. Methods In total, 56 joints (30 MCP and 26 PIP) from 9 patients (3 early RA patients diagnosis since 10 years, and 3 HC) were imaged by HR-pQCT (82 μm, Scanco XtremeCT), CR and MRI (Philips 3T). HR-pQCT images were scored for erosions by one reader according to a modified SPECTRA (Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis) algorithm. An erosion was defined as a cortical break seen on two consecutive slices in at least two planes (transverse, coronal or sagittal). MRI was independently scored for the presence of erosions, synovitis and BME by two radiologists. CRs were independently scored for the presence of erosions by one rheumatologist. Scoring of images was done on proximal and distal sites of MCP and PIP joints. Descriptive statistics were calculated. For the difference in total number of erosions on HR-pQCT, MRI and CR, Wilcoxon signed rank test was used. Results The total number of erosions detected was 62, 14 and 8 for HR-pQCT, MRI and CR respectively. Significantly more erosions were scored on HR-pQCT compared to, respectively, MRI and CR (p=.02 and p=.02). Erosions were scored in 7 out of 9 subjects on HR-pQCT, 3 out of 9 subjects on MRI and 2 out of 9 subjects on CR. Most erosions were scored in the late RA group (49 erosions on HR-pQCT, 12 on MRI and 6 on CR). Of the erosions in the late RA group, eleven erosions were detected on both HR-pQCT and MRI on the same joint site, and six of these erosions had concomitant synovitis and BME on MRI. Among the early RA patients, only 1 had synovitis and BME on MRI, but without erosions on HR-pQCT or CR. Conclusions HR-pQCT detects significantly more erosions than MRI and CR. The relation between scores of synovitis and BME on MRI and early detection of erosions with HR-pQCT needs to be further explored in a larger cohort and in longitudinal studies. References Stach. Arthritis Rheum. 2010; 330-339. Disclosure of Interest A. Scharmga: None declared, M. Peters: None declared, J. van den Bergh: None declared, D. Loeffen: None declared, B. van Rietbergen Consultant for: Scanco Medical AG, A. van Tubergen: None declared, R. Weijers: None declared, P. Geusens: None declared

Background Radiography is considered the gold standard for the detection of bone erosions in Rheumatoid arthritis (RA). Early detection of small erosions may potentially promote timely initiation of treatment and improve outcome. Small cortical breaks cannot be seen on radiographs, but can be detected with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT). Small cortical breaks can be seen in healthy controls (HCs) and can be the first stages of erosions in RA. Objectives To compare the number of cortical breaks in hand joints of RA patients and HCs according to their size. Methods Nineteen subjects (mean age ± SD; 53.9±8.0) from 3 different groups were evaluated: 1) 6 late RA, (diagnosis ≥10 years ago); 2) 6 early RA, (diagnosis ≤2 years ago); and 3) 7 HCs. From these subjects the 2nd MCP and PIP joints were imaged and evaluated with HR-pQCT (isotropic voxel size of 82 μm). In the RA groups, both hands were evaluated (24 joints per RA group), in the HC group only the dominant hand (total of 14 joints). A semi-automated algorithm was applied to the HR-pQCT images for the detection of cortical breaks. First, the outer margin of the bone structure was contoured. Second, the bone within 0.25 mm from this contour was defined as the cortical region. Last, different sizes for defining a cortical beak (>0.50mm, >0.66mm and >0.82mm) were applied and the number of breaks using each cut off was evaluated. Descriptive statistics were calculated and non-parametric tests for comparisons were performed. Results In the HC group, one joint was excluded due to movement artifacts; therefore, in total 61 joints could be evaluated (Late RA 24 joints, early RA 24 joints, HCs 13 joints). Table 1 shows the total number of breaks of each group stratified per cortical break size. Significant differences were found for break sizes >0.50mm and >0.82mm across the three different groups (p 0.50mm and >0.66mm (both p=0.07), and between early RA and late RA with breaks of >0.82mm (p=0.06). Most breaks were located close to the rim of the joint (Fig. 1). Conclusions The number and size of cortical breaks increases over the course of the disease in RA, with a significantly higher number of breaks in late RA compared to HCs. Therefore, the use of HR-pQCT in combination with our semi-automatic algorithm is a promising tool for early detection and monitoring of the number of small cortical breaks. Disclosure of Interest None declared

Background During recent years an increasing amount of generic alendronate formulations has become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Objectives Therefore, the objective of our study was to compare tolerability and efficacy of generic (GAln) and brand alendronate (BAln). Methods A randomized double-blinded single-centre cross-over study in postmenopausal women with osteoporosis using GAln and BAln in a cross-over setting, each for a period of 12 weeks with visits at baseline, week 4, 12, 16 and 24. Tolerance was evaluated by the Gastro-Intestinal Symptom Rating Scale (GSRS) and by self-reported side effects. Efficacy was assessed by bone turnover markers (CTX and PINP). Results 37 women (age; 65,4±6,4 years) were enrolled. Abdominal pain score at wk4 and wk16 was higher after GAln compared to BAln (B: 0,24; CI: 0,07- 0,4). After wk4 upper gastro-intestinal side effects (B: 0,20; CI: 0,03-0,33) and dyspepsia (B: 0,15; CI:0,02-0,28), were more reported after GAln. After adjustments for tolerance, BAln demonstrated a lower level of CTX than GAln at wk4 (B: 121,3;CI:51,98-190,5), but not at wk12 (B: 53,6; CI:-3,71-111). PINP was lower for women who received BAln at wk12 (B: 8,93;CI: 0,35-17,5). Conclusions In postmenopausal women with osteoporosis, generic alendronate caused significantly more gastro-intestinal side-effects during the first weeks of treatment. Markers of bone resorption and formation were significantly higher at week 4 and 12 with generic alendronate. Generic alendronate may not have the same tolerability and efficacy as branded alendronate. Disclosure of Interest None Declared

Background Patients presenting at a fracture liaison service (FLS) with a prevalent non-vertebral fracture have a high prevalence of vertebral fractures. However, the diagnosis of a vertebral fracture can only be based on imaging of the spine. VFA is a low-radiation method for diagnosing a vertebral fracture at the same time as a DXA is performed. Objectives To analyse the effect of systematic implementation of VFA in FLS patients on the diagnosis of prevalent vertebral fractures. Methods Systematic use of VFA to diagnose prevalent vertebral fractures in 352 consecutive patients presenting at the outpatient FLS of the Maastricht University Medical Centre for fracture risk evaluation because of a recent non-vertebral fracture, compared to 1000 patients who received standard care before the introduction of the FLS (pre-FLS). The presence of vertebral fractures with VFA and X-ray was evaluated semi-quantitatively according to the Genant score. Results In pre-FLS patients, 5% had a DXA, and no patient had a VFA. VFA was performed in 352 consecutive patients (mean age 65 yrs, 71% women) who were able and willing to participate in the FLS and had additional X-ray of the spine when indicated. Sixty patients (17%) had one or more vertebral deformities ≥ grade 1 on VFA (p Of these 60 patients, 30 (50%) had one or more moderate (grade 2) or severe (grade 3) vertebral deformities on VFA (9% of all patients). In 37 patients (11% of all patients) an additional X-ray was performed because of doubt about the degree of deformity (n=30) or an insufficient image quality (n=7) on VFA. Of these patients, 32 had a vertebral fracture ≥grade 2. As a result, 62 patients were diagnosed with a prevalent vertebral fracture (18% of all patients) and 22 of them (7% of all patients) had 2 or more vertebral fractures. Vertebral fractures were diagnosed in 23% of patients with osteoporosis (any T-score in spine or hip Conclusions Systematic implementation of VFA in FLS assessment resulted in the diagnosis of one or more previously unknown vertebral fractures in one out of five patients who attended the FLS with a recent non-vertebral fracture. In 11% of all patients an additional X-ray was performed to confirm or exclude a vertebral fracture. Disclosure of Interest None Declared

Background For the purpose of improving fracture risk assessment over bone mineral density (BMD), the FRAX® fracture risk prediction algorithm has been developed. Objectives To evaluate BMD and FRAX® in patients at the time they presented with a clinical fracture after the age of 50 years. Methods In 479 consecutive patients (75% women) who were able and willing to participate, we measured BMD in spine and hip and calculated the 10-year fracture riskusing FRAX®(calibrated for the Netherlands and calculated without and with BMD) for major fractures (FRAXMajor), for hip fracture (FRAXHip). Also the percentages of patients were estimated who, before the current fracture, had a FRAXMajor score ≥20% and FRAXHip ≥3% according to US guidelines (1), and FRAXMajor score above age-dependent variable thresholds for assessment (FRAXMajor≥As), and intervention (FRAXMajor≥Int) according to the European guidance (2). Results In 214 patients with a low-trauma major fracture, osteoporosis (BMD T-score ≤ -2.5) was present in 40% of patients, FRAXMajor≥20% in 12%, FRAXHip≥3% in 49%, FRAXMajor≥As in 47% and FRAXMajor≥Int in 7%. Adding BMD lowered the percentage of patients with FRAXMajor≥20% to 9% (p Int to 21% (p Int was found in 43% of patients with a low-trauma hip fracture and in 21% of patients with a first low-trauma major fracture. Lower percentages were found in the 265 patients with other fractures than low-trauma major fractures. Conclusions More than half of all evaluated patients presenting with a clinical fracture are not estimated by FRAX®to be at high fracture risk before the current fracture, even when they have a low-trauma major or hip fracture. These results draw attention to the fracture prevention paradox, by which only limited patients with a fracture are estimated to be at high risk, whether using FRAX®, without or with BMD, or using BMD alone. References www.nofstore.org Kanis, Osteoporosis Int. 2013 Jan;24(1):23-57. Disclosure of Interest None Declared