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.

Comparison of characteristics of patients with lung cancer in U.K. primary care databases: Clinical Practice Research Datalink Aurum and GOLD.

INTRODUCTION: In recent years, the number of general practices contributing to the Clinical Practice Research Datalink (CPRD) database GOLD is decreasing. Therefore, for research questions addressing for instance novel treatments requiring up-to-date data, sample size will become an important consideration in study feasibility. In recent years, CPRD Aurum, containing information of practices that use EMIS software, has become an additional data source that is being used for CPRD studies. In order to establish whether Aurum is suited to act as data source for future studies in the field of lung cancer research, we aimed to compare characteristics between patients with lung cancer in Aurum and GOLD. METHODS: A retrospective study was performed comparing characteristics and overall survival (OS) of patients with lung cancer in Aurum and GOLD. To further evaluate similarity, hypothetical eligibility of these patients in Aurum and GOLD was compared for 11 randomized clinical trials (RCTs). RESULTS: Baseline characteristics registered in Aurum and GOLD were largely similar, with some clinically irrelevant differences for previous malignancies, deviant laboratory values and drug use. Median OS was 9.8 and 9.0 months for patients in Aurum and GOLD, respectively. Potential RCT eligibility varied between 49.4% and 79.5% and 49.1% and 78.1% for patients in Aurum and GOLD, respectively. Mortality rates and the comparison of the obtained HRs per hypothetical eligibility cohort per RCT were similar in Aurum and GOLD. CONCLUSION: This study showed that data of patients with lung cancer in Aurum and GOLD are largely comparable, suggesting that Aurum is suitable for future epidemiological lung cancer research.

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.

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.

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.

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.

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.

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.

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.

Use of systemic glucocorticoids and the risk of major osteoporotic fractures in patients with sarcoidosis.

This study revealed the risk of major osteoporotic fracture in patients with sarcoidosis exposed to glucocorticoids. Current use of glucocorticoids was associated with a risk of fracture, with no difference between patients with and without sarcoidosis. Sarcoidosis per se was not associated with an increased fracture risk. INTRODUCTION: Sarcoidosis is a multi-organ, chronic inflammatory, granulomatous disorder that most frequently affects the lungs, lymph nodes, skin, eyes, and liver, but may occur in any organ, including the bones. While oral glucocorticoids (GCs) are commonly used as initial treatment, little is known about the risk of major osteoporotic fractures in patients with sarcoidosis exposed to GCs. METHODS: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1995 and December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) of major osteoporotic fractures in subjects with and without sarcoidosis stratified by average daily and cumulative dose exposures. RESULTS: A total of 376,858 subjects with a major osteoporotic fracture and the same number of subjects without this event were identified (mean age 64.2 ± 19.5 years, 69% female). In patients with sarcoidosis (n = 124), current use of GC was associated with an increased risk of major osteoporotic fracture (adjusted (adj.) OR 1.74; 95% CI 1.17-2.58), which dropped to baseline levels after discontinuation. In subjects without sarcoidosis, this risk was comparable (adj. OR 1.36; 95% CI 1.32-1.40). In sarcoidosis patients, cumulative dose 1.0-4.9 g and >10 g prednisolone equivalents were associated with increased risk of major osteoporotic fracture (adj. OR 2.75; 95% CI 1.06-7.14 and 2.22; 95% CI 1.17-4.22, respectively), whereas a cumulative dose of <1.0 g and 5.0-9.9 g was not associated with major osteoporotic fracture risk. CONCLUSION: Both in subjects with and without sarcoidosis, current expose to GC is associated with increased risk of major osteoporotic fractures, with no between-group difference. Sarcoidosis per se was not associated with increased fracture risk. Having sarcoidosis per se, i.e., if not treated with GC, is not a risk factor for fracture, and such patients may only need risk assessment when they commence GC therapy.

Risk of infections in patients with gout: a population-based cohort study.

To investigate the risk of various types of infections (pneumonia and urinary tract infection (UTI)), and infection-related mortality in patients with gout compared with population-based controls. A retrospective cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD). All patients with a first diagnosis of gout and aged >40 years between January 1987-July 2014, were included and matched with up to two controls. Time-varying Cox proportional hazards models were used to estimate the risk of infections and mortality. 131,565 patients and 252,763 controls (mean age: 64 years, 74% males, mean follow-up of 6.7 years) were included in the full cohort. After full statistical adjustment, the risk of pneumonia was increased (adj. HR 1.27, 95% CI 1.18 to 1.36), while the risk of UTI (adj. HR 0.99, 95% CI 0.97 to 1.01) was similar in patients compared to controls. No differences between patients and controls were observed for infection-related mortality due to pneumonia (adj. HR 1.03, 95% CI 0.93 to 1.14) or UTI (adj. HR 1.16, 95% CI 0.98 to 1.37). In conclusion, patients with gout did not have decreased risks of pneumonia, UTI or infection-related mortality compared to population-based controls.

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.

The epidemiology of fractures in Denmark in 2011.

UNLABELLED: In the present study, we used national health care databases to estimate fracture incidence rates (IRs) and compared these IRs based on imputed data. We showed that imputation could lead to both over- and underestimation of IRs, and future research should therefore focus on how to improve those imputations. INTRODUCTION: Osteoporosis is a major public health burden through associated (osteoporotic) fractures. In Denmark, the incidence rates (IRs) of hip fracture are widely available. However, there is limited data about other fracture sites. A recent report could only provide imputed IRs, although nationwide data is readily available in electronic healthcare databases. Therefore, our aim was to estimate fracture site-specific IRs for Denmark in 2011 and to compare those to the previously reported imputed data. METHODS: Data from the Danish National Hospital Discharge Register was used to estimate age- and gender-specific IRs for any fracture as well as for different fracture sites in the Danish population aged 20 years and older in 2011. Hip fracture IRs were stratified to sub-sites, and IRs were determined for all hip fractures which were confirmed by surgery. RESULTS: The total number of incident fractures in 2011 was 80,760 (IR 191, 95 % confidence interval (CI) 190-192 (per 10,000 person-years)), of which 35,398 (43.8 %, IR 171, 95 % CI 169-173) occurred in men and 45,362 (56.2 %, IR 211, 95 % CI 209-213) in women. The majority of the fractures occurred in the population aged 50 years and older (n = 50,470, IR 249, 95 % CI 247-251). The numbers of any hip fracture were lower than the previously imputed estimates, whereas the number of forearm fractures was higher. CONCLUSION: We showed age- and gender-specific fracture rates for any fracture as well as for different fracture sites. The IRs of most fracture sites increased with age. Estimating the number of fractures for Denmark based on imputation of data from other countries led to both over- and underestimation. Future research should therefore focus on how to improve those imputations as not all countries have nationwide registry data.

Use of incretin agents and risk of pancreatic cancer: a population-based cohort study.

AIM: To investigate the association between the use of incretin agents and the risk of pancreatic cancer. METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink, 2007-2012, was conducted. Patients (n = 182 428) with at least one non-insulin antidiabetic drug (NIAD) prescription and aged ≥18 years during data collection, were matched one-to-one to control patients without diabetes. Multivariable Cox proportional hazards models and a new user design were used to estimate the hazard ratio (HR) of pancreatic cancer in incretin users (n = 28 370) compared with control subjects without diabetes and other NIAD-treated patients. Time-dependent adjustments were made for age, sex, lifestyle, comorbidities and drug use. RESULTS: The mean duration of follow-up was 4.1 years for incretin users. Current NIAD use was associated with a fourfold increased risk of pancreatic cancer [HR 4.28, 95% confidence interval (CI) 3.49-5.24]. This risk was almost doubled among current incretin users as compared with control subjects. Incretin use was not associated with pancreatic cancer when compared with control subjects with diabetes (HR 1.36, 95% CI 0.94-1.96); however, the 'new user' design did show an association between incretin use and pancreatic cancer when compared with control subjects with diabetes. In both cohorts with prevalent and incident users of antidiabetic drugs, the risk of pancreatic cancer almost doubled in those who had recently initiated incretin therapy (up to seven prescriptions), whereas this elevated risk dropped to baseline levels with prolonged use. CONCLUSIONS: We found that incretin use was not associated with pancreatic cancer after adjustment for the severity of the underlying Type 2 Diabetes Mellitus (T2DM). The elevated risk of pancreatic cancer in those recently initiating incretin agents is likely to be caused by protopathic bias or other types of unknown distortion. The presence of considerable confounding by disease severity and the lack of a duration-of-use relationship do not support a causal explanation for the association between incretin agents and pancreatic cancer.

Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients.

AIM: The aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort). METHODS: We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti-diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP-4-inhibitors, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration. RESULTS: The inception cohort included 165,398 participants of whom 132,960 were metformin users and 32,438 were SU only users. During a mean follow-up time of more than 5 years 693 patients developed UBC, 124 of the control group and 461 of the all metformin users. There was no association between metformin use and UBC risk (HR = 1.12, 95% CI 0.90, 1.40) compared with SU only users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant. CONCLUSION: Metformin has no influence on the risk of UBC compared with SU in type 2 diabetes patients using a new user design.