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.

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.

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.

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.

Long-term functional outcome of distal radius fractures is associated with early post-fracture bone stiffness of the fracture region: An HR-pQCT exploratory study.

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 (µFEA) 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 (R2: 0.49, p = 0.006 and R2: 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 µFEA 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.

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.

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.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

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.

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.

Diagnosis of vertebral deformities on chest CT and DXA compared to routine lateral thoracic spine X-ray.

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.

A dedicated Fracture Liaison Service telephone program and use of bone turnover markers for evaluating 1-year persistence with oral bisphosphonates.

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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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% (< 415 ng/L) as LSC of s-CTX and > 36% (< 53.1 µg/L) as LSC of P1NP was determined optimally showing alendronate persistence after 1 year (being 93 and 88%, respectively). CONCLUSIONS: 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.

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.

Effect of implementation of guidelines on assessment and diagnosis of vertebral fractures in patients older than 50 years with a recent non-vertebral fracture.

We evaluated the impact of a new Dutch guideline on systematic implementation of densitometric Vertebral Fracture Assessment (VFA) in patients with a recent non-vertebral 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 association between insulin use and volumetric bone mineral density, bone micro-architecture and bone strength of the distal radius in patients with type 2 diabetes - The Maastricht study.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62±7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (ß):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (ß:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (ß:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (ß:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (ß:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (ß:-0.39 (95% CI:-0.62 to -0.17)) and failure load (ß:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.

Trends in oral anti-osteoporosis drug prescription in the United Kingdom between 1990 and 2012: Variation by age, sex, geographic location and ethnicity.

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 50years 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 10,000person-years (py). RESULTS: In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 2.3 to 169.7 per 10,000py), 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 10,000py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85-89years (248.9 per 10,000py in women and 119.3 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.