Cost-effectiveness analysis of fracture liaison services: a Markov model using Dutch real-world data.

This study assessed the lifetime cost-effectiveness of a fracture liaison service (FLS) compared to no-FLS in the Netherlands from a societal perspective and suggested that FLS was cost-effective in patients with a recent fracture aged 50 years and older. The implementation of FLS could lead to lifetime health-economic benefits. INTRODUCTION: The objective of this study was to investigate the lifetime cost-effectiveness of a fracture liaison service (FLS) compared to no-FLS in the Netherlands from a societal perspective and using real-world data. METHODS: Annual fracture incidence, treatment scenarios as well as treatment initiation in the years 2017-2019 were collected from a large secondary care hospital in the Netherlands. An individual-level, state transition model was designed to simulate lifetime costs and quality-adjusted life years (QALYs). Treatment pathways were differentiated by gender, presence of osteoporosis and/or prevalent vertebral fracture, and treatment status. Results were presented as incremental cost-effectiveness ratios (ICER). Both one-way and probabilistic sensitivity analyses were conducted. RESULTS: For patients with a recent fracture aged 50 years and older, the presence of an FLS was associated with a lifetime €45 higher cost and 0.11 additional QALY gained leading to an ICER of €409 per QALY gained, indicating FLS was cost-effective compared to no-FLS at the Dutch threshold of €20,000/QALY. The FLS remained cost-effectiveness across different age categories. Our findings were robust in all one-way sensitivity analyses, the higher the treatment initiation rate in FLS, the greater the cost-effective of FLS. Probabilistic sensitivity analyses revealed that FLS was cost-effective in 90% of the simulations at the threshold of €20,000/QALY, with women 92% versus men 84% by gender. CONCLUSION: This study provides the first health-economic analysis of FLS in the Netherlands, suggesting the implementation of FLS could lead to lifetime health-economic benefits.

Physical performance and sarcopenia assessment in patients with a recent fracture visiting the Fracture Liaison Service.

Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture. PURPOSE INTRODUCTION: Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means. METHODS: In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ - 2SD to < - 1 (impaired) and < - 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses. RESULTS: A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59-74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (P < 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (B) (95%CI) = - 0.25 [- 0.34, - 0.16]; hip: B = - 0.32 [- 0.47, - 0.17], VF: B = - 0.22 [- 0.34, - 0.11]), TUG; (major: B = - 0.54 [- 0.75, - 0.33]; hip: B = - 1.72 [- 2.08, -1.35], VF: B = - 0.61 [- 0.88, - 0.57]), 6MWT (major: B = - 0.34 [- 0.47, - 0.21]; hip: B = - 0.99 [- 1,22, - 0.77], VF: B = - 0.36 [- 0.53, - 0.19]). CONCLUSIONS: Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Physical Functioning in Patients with a Recent Fracture: The "Can Do, Do Do" Framework Applied to Explore Physical Capacity, Physical Activity and Fall Risk Factors.

Physical capacity (PC) and physical activity (PA) are associated physical performance measures, and combined, PC and PA are used to categorize physical performance in the "can do, do do" framework. We aimed to explore physical performance of patients attending the fracture liaison service (FLS). In this cross-sectional study, PC was measured by 6-min-walking-test (can't do/can do) and PA by accelerometer (don't do/do do). Following quadrants were defined based on predefined cut-off scores for poor performance: (1) "can't do, don't do"; (2) "can do, don't do"; (3) "can't do, do do"; (4) "can do, do do". Odds ratios (OR) were calculated and fall and fracture risk factors were assessed between quadrants. Physical performance of 400 fracture patients was assessed (mean age 64; female 70.8%). Patients performed as follows: 8.3% "can't do, don't do"; 3.0% "can do, don't do"; 19.3% "can't do, do do"; 69.5% "can do, do do". For the "can't do" group the OR for low PA was 9.76 (95% CI: 4.82-19.80). Both the "can't do, don't do" and "can't do, do do" group differed significantly compared to the "can do, do do" group on several fall and fracture risk factors and had lower physical performance. The "can do, do do" framework is able to identify fracture patients with an impaired physical performance. Of all FLS patients 20% "can't do, but "do do" while having a high prevalence of fall risk factors compared to persons that "can do, do do", which may indicate this group is prone to fall.

The pattern of incident fractures according to fracture site in people with T1D.

Higher incidences of fractures are seen in people with type 1 diabetes (T1D), but knowledge on different fracture sites is sparse. We found a higher incidence mainly for distal fracture sites in people with T1D compared to controls. It must be further studied which fractures attributed to the higher incidence rates (IRs) at specific sites. INTRODUCTION: People with T1D have a higher incidence of fractures compared to the general population. However, sparse knowledge exists on the incidence rates of individual fracture sites. Therefore, we examined the incidence of various fracture sites in people with newly treated T1D compared to matched controls. METHODS: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), of all ages with a T1D diagnosis code (n = 6381), were included. People with T1D were matched by year of birth, sex, and practice to controls (n = 6381). Fracture IRs and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex. RESULTS: The IR of all fractures was significantly higher in people with T1D compared to controls (IRR: 1.39 (CI95%: 1.24-1.55)). Compared to controls, the IRR for people with T1D was higher for several fracture sites including carpal (IRR: 1.41 (CI95%: 1.14-1.75)), clavicle (IRR: 2.10 (CI95%: 1.18-3.74)), foot (IRR: 1.70 (CI95%: 1.23-2.36)), humerus (IRR: 1.46 (CI95%: 1.04-2.05)), and tibia/fibula (IRR: 1.67 CI95%: 1.08-2.59)). In women with T1D, higher IRs were seen at the ankle (IRR: 2.25 (CI95%: 1.10-4.56)) and foot (IRR: 2.11 (CI95%: 1.27-3.50)), whereas in men with T1D, higher IRs were seen for carpal (IRR: 1.45 (CI95%: 1.14-1.86)), clavicle (IRR: 2.13 (CI95%: 1.13-4.02)), and humerus (IRR: 1.77 (CI95%: 1.10-2.83)) fractures. CONCLUSION: The incidence of carpal, clavicle, foot, humerus, and tibia/fibula fractures was higher in newly treated T1D, but there was no difference at other fracture sites compared to controls. Therefore, the higher incidence of fractures in newly treated people with T1D has been found mainly for distal fracture sites.

Health-related quality of life of patients with a recent fracture attending a fracture liaison service: a 3-year follow-up study.

This study explored the course of health state utility value over 3 years in patients with a recent fracture attending a Fracture Liaison Service and suggested that the overall change in health-related quality of life was not significant, although significant improvements were observed at 6 and 12 months compared to baseline. INTRODUCTION: To estimate the 3-year health-related quality of life (HRQoL) of patients with a recent fracture presenting at a Fracture Liaison Service (FLS) and to explore factors associated with health state utility value (HSUV). METHODS: Patients' HSUVs were derived from the EQ-5D-5L and SF-6D and calculated at six time points. Multiple imputation was applied for missing data. Linear mixed-effects regression analysis with random intercept and slope was applied to explore the course of HSUV over 3 years. The impact of subsequent fracture and the length of time between FLS visit and patients' index fracture on HSUV were also investigated. A backward stepwise elimination was applied to identify factors associated with HSUV. RESULTS: A total of 499 patients were included. The change of EQ-5D HSUV was not significant over 3-year follow-up (P = 0.52), although slightly but significantly higher HSUV was captured at 6 months (mean difference (MD): 0.015, P = 0.02) and 12 months (MD: 0.018, P = 0.01). There was no significant difference in the course of EQ-5D HSUV between fracture locations (P = 0.86). A significant increase in HSUV was only captured for patients had shorter time period (< 107 days) between FLS visit and their index fracture. Suffering a subsequent fracture was associated with significant QoL loss (MD: - 0.078, P < 0.001). Subsequent fracture, previous treatment with anti-osteoporosis medication, a prevalent vertebral fracture (grade 2 or 3), use of a walking aid, previous falls, and higher BMI were negatively associated with mean EQ-5D HSUV over 3 years. Comparable results were found using SF-6D HSUV. The lack of HRQoL data immediately after fracture and selection bias were two main limitations. CONCLUSION: The 3-year change in HSUV was not statistically significant, although significant improvements were observed at 6 and 12 months in comparison with baseline. Six factors were negatively associated with EQ-5D HSUV.

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions.

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.

The impact of fracture liaison services on subsequent fractures and mortality: a systematic literature review and meta-analysis.

This systematic review and meta-analysis suggests that fracture liaison service (FLS) is associated with a significantly lower probability of subsequent fractures and mortality although the latter was only found in studies comparing outcomes before and after the introduction of an FLS. INTRODUCTION: To systematically review and evaluate the impact of fracture liaison services (FLSs) on subsequent fractures and mortality using meta-analysis. METHODS: A literature search was performed within PubMed and Embase to identify original articles published between January 1, 2010, and April 30, 2020, reporting the effect of FLSs on subsequent fractures and/or mortality. Only studies comparing FLS to no-FLS were included. A meta-analysis using random-effects models was conducted. The quality of studies was appraised after combining and modifying criteria of existing quality assessment tools. RESULTS: The search retrieved 955 published studies, of which 16 studies fulfilled the inclusion criteria. Twelve studies compared outcomes before (pre-FLS) and after (post-FLS) FLS implementation, two studies compared outcomes between hospitals with and without FLS, and two other studies performed both comparisons. In total, 18 comparisons of FLS and no-FLS care were reported. Follow-up time varied from 6 months to 4 years. Sixteen comparisons reported on subsequent fractures and 12 on mortality. The quality assessment revealed methodological issues in several criteria. Excluding studies with very high selection bias, the meta-analysis of nine comparisons (in eight papers) revealed that the FLS care was associated with a significantly lower probability of subsequent fractures (odds ratio: 0.70, 95% CI: 0.52-0.93, P=0.01). In studies with a follow-up > 2 years, a significantly lower probability of subsequent fractures was captured for FLS care (odds ratio: 0.57, 95% CI: 0.34-0.94, P=0.03), while in studies ≤ 2 years, there was no difference in the odds of subsequent fractures. No significant difference in the odds of mortality was observed (odds ratio: 0.73, 95% CI: 0.49-1.09, P=0.12) in the meta-analysis of eight comparisons (in seven papers). However, a significantly lower probability of mortality was identified in the six pre-post FLS comparisons (odds ratio: 0.65, 95% CI: 0.44-0.95, P=0.03), but not in studies comparing hospitals with and without FLS. No difference was observed in mortality stratified by follow-up time. CONCLUSION: This systematic review and meta-analysis suggests that FLS care is associated with a significantly lower probability of subsequent fractures and mortality although the latter was only found in studies comparing outcomes before and after the introduction of an FLS. The quality assessment revealed that some important methodological issues were unmet in the currently available studies. Recommendations to guide researchers to design high-quality studies for evaluation of FLS outcomes in the future were provided.

Associations between bone attenuation and prevalent vertebral fractures on chest CT scans differ with vertebral fracture locations.

Vertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs. INTRODUCTION: Vertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7-T8 and T11-T12 ("cVFs") and less commonly at T4-T6 and T9-T10 ("lcVF"). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs. METHODS: Chest CT images of T4-T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex). RESULTS: On vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (p < 0.0001), 25% lower in subjects with lcVFs (p < 0.0001) and lowest in subjects with cVFs and lcVFs (- 32%, p < 0.0001). The highest ORs for presence of VFs per - 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6). CONCLUSIONS: The association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00292552.

Fracture Patterns in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review of Recent Literature.

PURPOSE OF REVIEW: In this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications. RECENT FINDINGS: T1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.

Bone mineral density and fractures in institutionalised children with epilepsy and intellectual disability.

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.

Association of secondary displacement of distal radius fractures with cortical bone quality at the distal radius.

INTRODUCTION: The aim of this study was to investigate the associations of patient characteristics, bone mineral density (BMD), bone microarchitecture and calculated bone strength with secondary displacement of a DRF based on radiographic alignment parameters. MATERIALS AND METHODS: Dorsal angulation, radial inclination and ulnar variance were assessed on conventional radiographs of a cohort of 251 patients, 38 men and 213 women, to determine the anatomic position of the DRF at presentation (primary position) and during follow-up. Secondary fracture displacement was assessed in the non-operatively treated patients (N = 154) with an acceptable position, preceded (N = 97) or not preceded (N = 57) by primary reduction (baseline position). Additionally, bone microarchitecture and calculated bone strength at the contralateral distal radius and tibia were assessed by HR-pQCT in a subset of, respectively, 63 and 71 patients. OUTCOME: Characteristics of patients with and without secondary fracture displacement did not differ. In the model with adjustment for primary reduction [OR 22.00 (2.27-212.86), p = 0.008], total [OR 0.16 (95% CI 0.04-0.68), p = 0.013] and cortical [OR 0.19 (95% CI 0.05-0.80], p = 0.024] volumetric BMD (vBMD) and cortical thickness [OR 0.13 (95% CI 0.02-0.74), p = 0.021] at the distal radius were associated with secondary DRF displacement. No associations were found for other patient characteristics, such as age gender, BMD or prevalent vertebral fractures. CONCLUSIONS: In conclusion, our study indicates that besides primary reduction, cortical bone quality may be important for the risk of secondary displacement of DRFs.

Characterization of fracture liaison service non-responders after invitation by home visits and questionnaires.

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.

Diabetes and fractures: new evidence of atypical femoral fractures?

Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures. INTRODUCTION: Patients with diabetes have an increased risk of femoral fractures, but little is known about the risk of atypical femoral fractures (AFFs). The aim of this study was to identify the risk of subtrochanteric and femoral shaft (ST/FS) fractures and estimate the risk of AFFs in patients with type 1 (T1D) and type 2 diabetes (T2D). METHODS: From the nationwide Danish National Patient Register, we identified patients with T1D (n = 19,896), T2D (n = 312,188), and sex- and aged-matched controls without diabetes (n = 996,252) from the general population and all ST/FS fractures (n = 7509). Data were analyzed using a Cox proportional-hazards model and the incidence rate and rate ratio of ST/FS fractures were estimated. RESULTS: The incidence rate of ST/FS fractures in T1D was 52.14 events per 100,000 person years and 73.21 per 100,000 person years in T2D. T1D was associated with an increased risk of ST/FS (HR 2.07 (95% CI 1.68-2.56)), whereas T2D was not (HR 0.99 (95% CI 0.94-1.10)). Previous ST/FS fractures were associated with an increased risk of subsequent ST/FS fractures (HR 6.95 (95% CI 6.00-8.05)) and the use of bisphosphonates with an increased risk of ST/FS fractures (HR 1.72 (95% CI 1.54-1.91)). CONCLUSION: Patients with T1D have a higher risk of ST/FS fractures compared with sex- and age-matched controls. Since a proportion of ST/FS fractures are classified as AFFs, this could point towards the fact that AFFs also are increased in patients with T1D, but not T2D.

The risk of new fragility fractures in patients with chronic kidney disease and hip fracture-a population-based cohort study in the UK.

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.

Association between vertebral fractures and coronary artery calcification in current and former smokers in the ECLIPSE cohort.

In smokers and former smokers from the ECLIPSE cohort, there is an association between prevalent vertebral fractures (VFs) and coronary artery calcification (CAC). Chest CT scans provide the opportunity to evaluate VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions. INTRODUCTION: Prevalence of VFs among smokers and patients with chronic obstructive pulmonary disease (COPD) is high, and an association between CAC and osteoporosis has been described. We investigated the associations between VFs and CAC (expressed in Agatston score) in (former) smokers. METHODS: Current and former smokers from the ECLIPSE study (designed to determine underlying COPD progression mechanisms) were studied. Baseline Agatston score (zero (0), medium (1-400), or high (> 400)), baseline bone attenuation (BA), and prevalent and incident VFs (vertebrae T1-L1) were assessed on CT. RESULTS: A total of 586 subjects were included (mean age 59.8 ± 8.3; 62.3% men; 70.1% with COPD; 21.0% with prevalent VFs; 196 with zero, 266 with medium, and 124 with high Agatston score). Of these, 23.4% suffered incident VFs within 3 years. In multivariate models, prevalent VFs were associated with medium (1.83 [95% CI 1.01-3.30]) and with high (OR = 3.06 [1.45-6.47]) Agatston score. After adjustment for BA, prevalent VFs were still associated with high (OR = 2.47 [1.13-5.40]), but not significantly with medium Agatston score (OR = 1.57 [0.85-2.88]). Similarly, after adjustment for BA, high (OR = 2.06 [1.02-4.13]) but not medium Agatston score (OR = 1.61 [0.88-2.94]) was associated with prevalent VFs. Agatston score at baseline was not associated with short-term VF incidence. CONCLUSION: In (former) smokers, there was an association between prevalent VFs and Agatston score. Chest CT scans provide the opportunity to also evaluate for VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.

Glucose-Lowering Drugs and Fracture Risk-a Systematic Review.

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. 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.

The Feasibility of High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Patients with Suspected Scaphoid Fractures.

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 (<1.0%). 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.

Challenges and opportunities to improve fracture liaison service attendance: fracture registration and patient characteristics and motivations.

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.

Vertebral bone attenuation in Hounsfield Units and prevalent vertebral fractures are associated with the short-term risk of vertebral fractures in current and ex-smokers with and without COPD: a 3-year chest CT follow-up study.

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.