Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges.

Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length-dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared with axial angle data of 13 young women. In the scans without a deviated axial angle and compared with normative HR-pQCT data, Z-scores at the radius for trabecular bone mineral density (BMD), number, and separation were -1.6 ± 1.3, -2.5 ± 1.4, and -2.7 (IQR: 2.7), respectively. They were -1.4 ± 1.5 and -1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed, most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores <-4 or >4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.

OI is a rare condition with large clinical heterogeneity. One of the major characteristics associated with OI is the increased fracture risk due to defects in bone structure and material. Data on the defects in bone structure at the micrometer level (i.e. bone microarchitecture) are scarce. Bone microarchitecture can be assessed noninvasively using HR-pQCT, but its use in OI has not extensively been described. Yet, potential challenges may arise related to among others the occurrence of short extremities and skeletal deformities in OI. We assessed bone microarchitecture and strength in 118 adults with OI types I, III, or IV using HR-pQCT with an extremity-length-dependent scan protocol. Additionally, we evaluated potential challenges of using HR-pQCT in this cohort. Our results demonstrated that predominantly trabecular microarchitecture­especially trabecular number and separation­and overall bone strength were impaired in adults with OI as compared with normative data. Furthermore, we observed various microarchitectural inhomogeneities, most pronounced being trabecular void volumes. Regarding applicability, HR-pQCT could be used without challenges in most adults with OI. However, deviations in scan region may potentially influence HR-pQCT parameters, and standard HR-pQCT analyses may not always give accurate results due to microarchitectural inhomogeneities nor fully reflect all microarchitectural inhomogeneities.

PPI use is not associated with bone microarchitecture and strength assessed with HR-pQCT after three-years follow-up in patients visiting the Fracture Liaison Service.

BACKGROUND: The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS). METHODS: This three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56-69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females). RESULTS: In total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use. CONCLUSION: Compared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies.

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.

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 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.

Assessment of Trabecular Bone Score: a 7-year follow-up study in institutionalized adults with refractory epilepsy and intellectual disability.

PURPOSE: The aim of this longitudinal study was to assess trabecular bone scores (TBS) in institutionalized adults with refractory epilepsy and intellectual disability and to study the association of TBS and incident fractures during seven years of follow-up. METHODS: In 2009 and 2016, all institutionalized adult patients of a long-stay care facility in the Netherlands (n=261) were invited to undergo a dual-energy X-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and assessment of TBS. Vertebrae T4-L4 were analyzed using quantitative morphometry. New and worsening vertebral fractures (VFs) were considered as incident VFs. Data regarding clinical fractures were extracted from the medical files. Patients were treated with anti-osteoporosis medication according to the Dutch guideline. RESULTS: Baseline and follow-up DXA, VFA and TBS could be obtained in 136 patients (83 male) aged between 18 and 79 years old (44.7±15.5). At baseline, 36 patients (26.5%) were diagnosed with osteoporosis, 68 (50.0%) with osteopenia and 32 patients (23.5%) had a normal bone mineral density (BMD). As for TBS, 26 patients (19.1%) had a partially degraded microarchitecture and 26 patients (19.1%) a degraded microarchitecture. During seven years of follow-up, 80 patients (59%) sustained at least one fracture, of which 28 patients (35%) had one or more major osteoporotic fractures. Thirty-four patients (25.0%) had at least one new or worsening morphometric VF. Compared to baseline, TBS significantly decreased over seven years of follow-up in non-treated patients (-0.039±0.064, p<.001). In patients who were treated with bisphosphonates for more than one year during follow-up, TBS did not change significantly (p=.093). In multivariate analyses, no significant associations were found between TBS at baseline and incident fractures during follow-up. CONCLUSION: In this study, we found a high incidence of fractures and TBS decreased significantly over seven years of follow-up in non-treated institutionalized adult patients with refractory epilepsy and intellectual disability, but TBS was not associated with incident fractures.

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.

Assessment of the healing of conservatively-treated scaphoid fractures using HR-pQCT.

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.

Incidence of clinical fractures: A 7-year follow-up study in institutionalized adults with epilepsy and intellectual disability.

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<.001). 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.

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.

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.

Improved Detection of Scaphoid Fractures with High-Resolution Peripheral Quantitative CT Compared with Conventional CT.

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.

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.

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.

The association between prevalent vertebral fractures and bone quality of the distal radius and distal tibia as measured with HR-pQCT in postmenopausal women with a recent non-vertebral fracture at the Fracture Liaison Service.

We evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration. INTRODUCTION: We evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service. METHODS: In this cross-sectional study in women aged 50-90 with a recent non-vertebral fracture (NVF), VFs were identified on lateral spine images by dual-energy X-ray absorptiometry. Bone micro-architecture and strength were measured at the non-dominant distal radius and distal tibia using HR-pQCT. Linear regression analyses were used to estimate the association between prevalent VFs and HR-pQCT parameters. RESULTS: We included 338 women of whom 74 (21.9%) women had at least one prevalent VF. After adjustment for femoral neck aBMD (FN aBMD) and other parameters, women with at least one prevalent vertebral fracture had significantly lower total and trabecular vBMD and trabecular number (ß - 16.7, - 11.8, and - 7.8 in the radius and - 21.4, - 16.6, and - 7.2 in the tibia, respectively), higher trabecular separation at the radius and tibia (ß 9.0 and 9.3, respectively), and lower cortical thickness and calculated ultimate failure load and compressive bone strength at the tibia (ß - 5.9, - 0.6, and - 10.9, respectively) as compared with those without prevalent VFs. Furthermore, more severe prevalent VFs were associated with even lower total and trabecular vBMD and lower ultimate failure load and compressive stiffness at the radius and tibia, and lower trabecular number and higher trabecular separation at the radius. CONCLUSION: This study indicates that the presence and severity of prevalent VFs reflect generalized bone deterioration in women with a recent NVF, independently of FN aBMD.

Two-year persistence with teriparatide improved significantly after introduction of an educational and motivational support program.

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 < 0.001). Overall, the risk of non-persistence was 28% lower in the EMSP compared with the BSP group (HR: 0.72; 95% CI: 0.55-0.93). CONCLUSION: The introduction of the EMSP has demonstrated to improve the persistence with TPTD, resulting in 78% of the patients being persistent with TPTD during the 2-year treatment period.

All-cause mortality with current and past use of antidepressants or benzodiazepines after major osteoporotic and hip fracture.

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 (< 30 days before) was not. 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.

Incidence of subsequent fractures in the UK between 1990 and 2012 among individuals 50 years or older.

We 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. INTRODUCTION: Recent 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Patients 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.

Comorbidities and medication use in patients with a recent clinical fracture at the Fracture Liaison Service.

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.

The influence of bone mineral density and cortical index on the complexity of fractures of the proximal humerus.

OBJECTIVES: The goal of this study is to investigate the relation between indicators of osteoporosis (i.e., bone mineral density (BMD), and Cortical Index (CI)) and the complexity of a fracture of the proximal humerus as a result of a low-energy trauma. METHODS: A retrospective chart review of 168 patients (mean age 67.2 years, range 51 to 88.7) with a fracture of the proximal humerus between 2007 and 2011, whose BMD was assessed at the Fracture Liaison Service with Dual Energy X-ray Absorptiometry (DXA) measurements of the hip, femoral neck (FN) and/or lumbar spine (LS), and whose CI and complexity of fracture were assessed on plain anteroposterior radiographs of the proximal humerus. RESULTS: No significant differences were found between simple and complex fractures of the proximal humerus in the BMD of the hip, FN or LS (all p > 0.3) or in the CI (p = 0.14). Only the body mass index was significantly higher in patients with a complex fracture compared with those with a simple fracture (26.9 vs 25.2; p = 0.05). CONCLUSION: There was no difference in BMD of the hip, FN, LS or CI of the proximal humerus in simple compared with complex fractures of the proximal humerus after a low-energy trauma. Factors other than the BMD and CI, for example body mass index, may play a more important role in the complexity of this fracture.Cite this article: J.W.A.M. den Teuling, B.S. Pauwels, L. Janssen, C.E. Wyers, H. M. J. Janzing, J.P.W. van den Bergh, J. W. Morrenhof. The Influence of bone mineral density and cortical index on the complexity of fractures of the proximal humerus. Bone Joint Res 2017;6:584-589. DOI: 10.1302/2046-3758.610.BJR-2017-0080.