Background Inhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established. Methods We conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated. Results There was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively. Conclusions The findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

Introduction: Osteoporosis and fragility fractures are associated with corticosteroids which are the mainstay treatment for asthma; however, these bone comorbidities within asthma need to be better described.Methods: A matched cohort study was conducted using the UK Clinical Practice Research Database (CPRD). Adults with an incident asthma code were identified and matched, with up to four randomly selected people without asthma, by age, sex and practice. Osteoporosis and fragility fracture incidence rates were calculated, and Cox regression was performed comparing hazard rates to the general population. We report the impact of age, sex, glucocorticoids and the risk of specific fractures.Results: Patients with asthma had a higher risk of osteoporosis (adjusted hazard ratio (aHR) 1.18, 95% CI 1.13–1.23) and were 12% (aHR 1.12, 95% CI 1.07–1.16) more likely to sustain fragility fractures than the general population. Age modified the effect of asthma on osteoporosis and fragility fractures, such that the effect was stronger in younger people (p_interaction<0.0001). The vertebra (aHR 1.40, 95% CI 1.33–1.48) and forearm/wrist (aHR 1.27, 95% CI 1.22–1.32) were the sites linked with a larger incidence. A dose–response relationship between oral corticosteroids (OCS) and osteoporosis was observed, whereas the risk of fragility fractures increased in those with six or more OCS courses per year. Regular use of inhaled corticosteroids (ICS) increased the risk of both bone conditions.Conclusions: Patients with asthma are more likely to develop osteoporosis or sustain fragility fractures than the general population, with a particular concern in younger people and those more frequently using OCS and ICS.

Co-existing long-term conditions (LTC) in psoriasis and their potential causal associations with the disease are not well-established. This study aims to determine distinct clusters of LTC in people with psoriasis and the potential bi-directional causal association between these LTC and psoriasis. Using latent class analysis, cross-sectional data of people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related co-morbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTC. Two-sample bidirectional Mendelian randomisation (MR) analysis assessed potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10^-8). Five co-morbidity clusters were identified in a population of 10,873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure (rg = 0.23, p = 8.8 × 10⁻⁸), depression (rg = 0.12, p = 2.7 × 10⁻⁵), coronary artery disease (CAD) (rg = 0.15, p = 2 × 10⁻⁴), and type 2 diabetes (rg = 0.19, p = 3 × 10⁻³). Genetic liability to CAD was associated with an increased risk of psoriasis (OR_IVW = 1.159; 95%CI 1.055-1.274; p = 2 × 10⁻³). The MR-PRESSO (OR_MR-PRESSO = 1.13; 95%CI 1.042-1.228; p = 6 × 10⁻³) and the MR-RAPS (OR_MR-RAPS = 1.149; 95%CI 1.062-1.242; p = 5 × 10⁻⁴) approaches corroborate the IVW findings. The weighted median generated similar and consistent effect estimates but was not statistically significant (OR_WM = 1.076; 95%CI 0.949-1.221; p = 0.251). Evidence for a suggestive increased risk was detected for CAD (OR_IVW = 1.031; 95%CI 1.003-1.059; p = 0.032) and heart failure (OR_IVW = 1.019; 95%CI 1.005-1.033; p = 9 × 10⁻³) in those with genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance. Five distinct clusters of psoriasis co-morbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Co-existing LTC share with psoriasis common genetic and non-genetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted coronary artery disease is possibly associated with an increased risk of psoriasis, altering our prior knowledge.

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have clinical, pathological and genetic overlapping. Lipid pathways are implicated in ALS. This study examined the effect of blood lipid levels on ALS, FTD risk, and survival in ALS. Methods: A systematic review and meta-analysis of high and low-density lipoprotein cholesterol (HDL-c and LDL-c), total cholesterol, triglycerides, apolipoproteins B and A1 levels with ALS was performed. Two-sample Mendelian randomisation (MR) analysis sought the causal effects of these exposures on ALS, FTD, and survival in ALS. The effect of lipid-lowering drugs was also examined using genetic proxies for targets of lipid-lowering medications. Results: Three cohort studies met the inclusion criteria for meta-analysis. Meta-analysis indicated an association between higher LDL-c (HR_{per mmol/L} = 1.07, 95%CI:1.02–1.12; $${I}^{2}$$I 2 =18%) and lower HDL-c (HR_{per mmol/L} = 0.83, 95%CI:0.74–0.94; $${I}^{2}$$I 2 =0%) with an increased risk of ALS. MR suggested causal effects of higher LDL-c (OR_IVW = 1.085, 95%:CI 1.008–1.168, p_FDR = 0.0406), total cholesterol (OR_IVW = 1.081, 95%:CI 1.013–1.154, p_FDR = 0.0458) and apolipoprotein B (OR_IVW = 1.104, 95%:CI 1.041–1.171, p_FDR = 0.0061) increasing ALS risk, and higher apolipoprotein B level increasing FTD risk (OR_IVW = 1.424, 95%CI 1.072–1.829, p_FDR = 0.0382). Reducing LDL-c through APOB inhibition was associated with lower ALS (OR_IVW = 0.84, 95%CI 0.759–0.929, p_FDR = 0.00275) and FTD risk (OR_IVW = 0.581, 95%CI 0.387–0.874, p_FDR = 0.0362). Conclusion: These data support the influence of LDL-c and total cholesterol on ALS risk and apolipoprotein B on the risk of ALS and FTD. Potential APOB inhibition might decrease the risk of sporadic ALS and FTD. Further work in monogenic forms of ALS and FTD is necessary to determine whether blood lipids influence penetrance and phenotype.