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Purpose: People with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D., Methods: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls., Results: The crude HRs for any fracture (HR: 1.30, CI95%: 1.11-1.51), lower-arm (HR: 1.22, CI95%: 1.00-1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11-2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70-2.36; MOFs: HR: 1.89, CI95%: 1.44-2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53-2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34-3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20-1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21-1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47-3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10-2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67-0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38-0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0-4 years: HR: 1.20, CI95%: 1.00-1.44; 5-9 years: HR: 1.17, CI95%: 0.91-1.50; <10 years: HR: 0.83, CI95%: 0.54-1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04-1.95)., Conclusion: The overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones., Competing Interests: Declaration of competing interest Peter Vestergaard is head of research in the Steno Diabetes Center North Denmark sponsored by the Novo Nordisk Foundation. Joop van den Bergh: unrestricted research grant and lecture fee from Amgen and UCB, is consultant for PoroUS. Nicklas H. Rasmussen holds shares in Novo Nordisk, has lecture fees from Boehringer Ingelheim and travel expenses from UCB. The other authors Johanna Driessen, Patrick Souverein and Annika Kvist declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the hazard ratios (HR) for various fracture sites and identify associated risk factors in a cohort of relatively healthy adult people with newly diagnosed type 1 diabetes (T1D)., Methods: The study utilized data from the UK Clinical Practice Research Datalink GOLD (1987-2017). Participants included people aged 20 and above with a T1D diagnosis code (n = 3281) and a new prescription for insulin. Controls without diabetes were matched based on sex, year of birth, and practice. Cox regression analysis was conducted to estimate HRs for any fracture, major osteoporotic fractures (MOFs), and peripheral fractures (lower-arm and lower-leg) in people with T1D compared to controls. Risk factors for T1D were examined and included sex, age, diabetic complications, medication usage, Charlson comorbidity index (CCI), hypoglycemia, previous fractures, falls, and alcohol consumption. Furthermore, T1D was stratified by duration of disease and presence of microvascular complications., Results: The proportion of any fracture was higher in T1D (10.8 %) than controls (7.3). Fully adjusted HRs for any fracture (HR: 1.43, CI95%: 1.17-1.74), MOFs (HR: 1.46, CI95%: 1.04-2.05), and lower-leg fractures (HR: 1.37, CI95%: 1.01-1.85) were statistically significantly increased in people with T1D compared to controls. The primary risk factor across all fracture sites in T1D was a previous fracture. Additional risk factors at different sites included previous falls (HR: 1.64, CI95%: 1.17-2.31), antidepressant use (HR: 1.34, CI95%: 1.02-1.76), and anxiolytic use (HR: 1.54, CI95%: 1.08-2.29) for any fracture; being female (HR: 1.65, CI95%: 1.14-2.38) for MOFs; the presence of retinopathy (HR: 1.47, CI95%: 1.02-2.11) and previous falls (HR: 2.04, CI95%: 1.16-3.59) for lower-arm and lower-leg fractures, respectively. Lipid-lowering medication use decreased the risk of MOFs (HR: 0.66, CI95%: 0.44-0.99). Stratification of T1D by disease duration showed that the relative risk of any fracture in T1D did not increase with longer diabetes duration (0-4 years: HR: 1.52, CI95%: 1.23-1.87; 5-9 years: HR: 1.30, CI95%: 0.99-1.71; <10 years: HR: 1.07, CI95%: 0.74-1.55). Similar patterns were observed for other fracture sites. Moreover, the occurrence of microvascular complications in T1D was linked to a heightened risk of fractures in comparison to controls. However, when considering the T1D cohort independently, the association was not statistically significant., Conclusion: In a cohort of relatively healthy and newly diagnosed people with T1D HRs for any fracture, MOFs, and lower-leg fractures compared to controls were increased. A previous fracture was the most consistent risk factor for a subsequent fracture, whereas retinopathy was the only diabetes related one. We postulate a potential initial fracture risk, succeeded by a subsequent risk reduction, which might potentially increase in later years due to the accumulation of complications and other factors., Competing Interests: Declaration of competing interest Peter Vestergaard is head of research in the Steno Diabetes Center North Denmark sponsored by the Novo Nordisk Foundation. Joop van den Bergh: unrestricted research grant and lecture fee from Amgen and UCB, is consultant for PoroUS. Nicklas H. Rasmussen holds shares in Novo Nordisk, has lecture fees from Boehringer Ingelheim and travel expenses from UCB. The other authors Johanna Driessen, Patrick Souverein and Annika Kvist declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures., Methods: A case-control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date., Results: We identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69-2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16-1.63 and 1.40, 95% CI 1.06-1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63-2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19-1.72 (medium) and OR 1.32 95% CI 0.98-1.79 (low) (p<0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend., Conclusions: The extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objectives: To assess and compare the risk of prostatic surgery in (subsets of) patients with a diagnosis of BPH. We sought to expand on data of an earlier pharmacy-based study by obtaining more information on BPH disease parameters by using a Dutch GP-based research database., Methods: A retrospective cohort study (1994-mid-year 2002) was conducted among 1430 men aged > or =45 years with > or =6 months of registration with the GP. BPH case identification was based on review of medical records., Results: Overall, we found that there was no difference in the risk of prostatic surgery between patients on medical treatment and watchful waiting. Patients using 5alpha-reductase inhibitors (5-ARIs) at any stage had a statistically significant reduced risk of surgery compared to patients using alpha-blockers only: adjusted hazard ratio 0.35 (95%CI: 0.13-0.96). The routine collection of BPH parameters were insufficient to be useful in the analysis., Conclusion: Patients using 5-ARIs seemed to have a reduced risk of prostatic surgery compared to patients using alpha-blockers. However, it was unknown whether the disease profile of 5-ARI users is different compare to non-5-ARI-treated and untreated patients with BPH, as detailed medical information necessary to characterise patients according to the BPH disease severity and development of disease parameters is not routinely recorded by GPs.

Objective: To investigate whether there is a difference in the risk of progressing to BPH-related prostatic surgery between patients using alpha-blockers and patients using the 5-alpha-reductase inhibitors (5-ARIs)., Methods: A population-based cohort study was conducted, using data from the PHARMO Record Linkage System. We identified 5671 patients (> or =50 years old, no history of using both alpha-blockers and 5-ARIs, more than one year of database history prior to the first date of BPH drug-dispensing), who filled at least one prescription for either alpha-blockers (alfuzosin, tamsulosin, terazosin) or 5-ARIs (finasteride). The incidence of BPH-related surgery was compared between patients treated with alpha-blockers and patients treated with 5-ARIs., Results: The cumulative incidence of BPH-related prostatic surgery was 15.2% and mainly involved transurethral resection of the prostate (TURP) (13.4%). Patients using alpha-blockers had a significantly increased risk of BPH-related prostatic surgery compared to patients using 5-ARIs, which remained after adjusting for age, calendar time, type of prescriber and chronic disease score (adjusted HR: 1.52, 95% CI: 1.24-1.88). The difference between alpha-blockers and 5-ARIs was sustained after stratification of time period (<1995, > or =1995) and exclusion of patients with prostatic surgery within one month of treatment initiation., Conclusions: It is concluded that alpha-blocker treated patients had a higher risk of BPH-related surgery compared to 5-ARI treated patients. Additional research on the long-term outcomes and risk factors for the natural progression of BPH is necessary to identify the optimal medical treatment for BPH patients according to their baseline characteristics.

Objective: Given the high possibility of co-occurrence of benign prostatic hyperplasia (BPH) and cardiovascular disease, we evaluated whether patients using BPH drugs are at an increased risk of acute hospital admission for ischemic heart disease (IHD)., Methods: A nested case control study within a cohort of 4414 men (aged > or =30 years) who had a history of using BPH products between 1992 and 1998 was conducted. Cases were defined as men with a first record of an acute hospital admission for IHD during the study period; three controls were matched to each case on year of birth, pharmacy and calendar time (index date)., Results: The study population comprised 220 cases and 515 controls. Current use of alpha-blockers (adjusted odds ratio 1.0, 95% confidence interval: 0.5-2.2) or finasteride (adjusted odds ratio 0.3, 95% CI: 0.1-1.4) was not associated with hospital admission for IHD. Furthermore, current use of BPH drugs was not associated with IHD in patient subgroups (age, history of cardiovascular disease, diabetes), nor with duration of use prior to hospitalization., Conclusion: Although the power of the study was low, we found no evidence for an association between current use of BPH drugs and hospital admission for IHD. Therefore, our study seems to confirm the good cardiovascular safety profile of modern BPH drugs.