Glucocorticoids Are Not Associated with Bone Mineral Density in Patients with Polymyalgia Rheumatica, Giant Cell Arteritis and Other Vasculitides-Cross-Sectional Baseline Analysis of the Prospective Rh-GIOP Cohort.

BACKGROUND: Glucocorticoids (GCs) can cause osteoporosis (OP). Prior observational research on bone density and the effects of GCs in polymyalgia rheumatica (PMR) and vasculitides is scarce and inconclusive. METHODS: Rh-GIOP is a prospective cohort study of bone health in patients with inflammatory rheumatic diseases. In this cross-sectional baseline analysis, we focused on patients with PMR and different forms of vasculitides. Multivariable linear regression was used to model the effect of current and cumulative GC intake on the minimum T-score at any site (mTs; at either lumbar spine or hip), with comprehensive adjustment for confounders. In separate models, GCs were modelled both as continuous and categorical predictors. Sensitivity analyses, stratifying by measurement site and disease, were conducted. RESULTS: A total of 198 patients, with a mean age of 67.7 ± 11.4 years and a mean disease duration of 5.3 ± 6.3 years, were included. Most patients suffered from PMR (36%), giant cell arteritis (26%) or granulomatosis with polyangiitis (17%). Women comprised 66.7% of the patients, and 87.4% were currently taking GCs. The mean CRP was 13.2 ± 26.1 mg/L. OP diagnosed by dual energy X-ray absorptiometry (DXA) (T-score ≤ -2.5) was present in 19.7% of the patients. While 88% were taking vitamin D supplements, calcium supplementation (4%) and treatment with anti-resorptive agents (17%) were relatively infrequent. Only 7% had a vitamin D deficit. Neither current (ß(continuous model) = -0.01, 97.5% CI -0.02 to 0.01; p(all models) ≥ 0.49) nor cumulative (ß(continuous model) = 0.01, 97.5% CI -0.04 to 0.07; p(all models) ≥ 0.35) GC doses were associated with mTs in any model. CRP was not associated with mTs in any model (p(all models) ≥ 0.56), and no interaction between CRP and GC intake was observed (p for interaction(all models) ≥ 0.32). Across all analyses, lower body mass index (p(all models) ≤ 0.01), history of vertebral fractures (p(all models) ≤ 0.02) and proton-pump inhibitor intake (p(all models) ≤ 0.04) were associated with bone loss. Sensitivity analyses with femoral neck and lumbar spine T-scores as dependent variables led to similar results as the analysis that excluded patients with PMR. CONCLUSIONS: In this cohort of PMR and vasculitides, we found a similar prevalence of OP by DXA to the overall elderly German population. Vitamin D supplementation was very common, and vitamin D insufficiency was less frequent than expected in Germans. There was no association between current or cumulative GC intake, CRP and impaired bone density. Proton-pump inhibitors seem to be a major, but somewhat neglected, risk factor for OP and should be given more attention. Our findings require confirmation from longitudinal analyses of the Rh-GIOP and other cohorts.

Effects of Calcium and Vitamin D Co-supplementation on the Lipid Profile: A Systematic Review and Meta-analysis.

PURPOSE: Calcium and vitamin D co-supplementation is common and widely used, but randomized, controlled trials (RCTs) have yielded inconclusive results concerning its impact on the serum lipid profile. METHODS: A comprehensive literature search of Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinical trial registry databases was conducted to identify placebo-controlled RCTs that were published through September 2020 and that evaluated the impact of calcium and vitamin D co-supplementation on total cholesterol (TC), triglycerides (TGs), low- and very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C). Standardized mean differences (SMDs) were pooled using random-effects meta-analysis models. FINDINGS: Thirteen studies in a total of 2304 participants met the inclusion criteria. Calcium and vitamin D co-supplementation was associated with significant reductions in both TC (SMD, -0.81; 95% CI, -1.35 to -0.27; I2 = 94.6%) and TGs (SMD, -0.50; 95% CI, -0.91 to -0.08; I2 = 91.5%), and with a significant increase in HDL-C (SMD, 1.22; 95% CI, 0.60 to 1.83; I2 = 95.4%). However, calcium and vitamin D co-supplementation were not found to be associated with significantly decreased low-density lipoprotein cholesterol (SMD, -0.39; 95% CI, -0.78 to 0.01; I2 = 90.1%) or very-low-density lipoprotein cholesterol (SMD, -0.01; 95% CI, -0.70 to 0.69; I2 = 82.3%). IMPLICATIONS: The findings from the present systematic review and meta-analysis suggest that calcium and vitamin D co-supplementation has a beneficial effect on TC, TG, and HDL-C. Larger-scale, well-designed RCTs are needed to clarify the effect of calcium and vitamin D co-supplementation on all lipid-profile components.

Effects of coffee consumption on arterial stiffness and endothelial function: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Endothelial function (EF) and arterial stiffness (AS) are predictors of cardiovascular disease. As previous research concerning the effect of coffee intake on EF and AS was controversial, we conducted a systematic review and meta-analysis to synthesize research. METHODS: We performed a systematic search in PubMed, Scopus and Web of Science to find clinical trials investigating the effect of coffee intake on EF or AS up to March 2020.Random-effects models were used to estimate the pooled weighted mean difference (WMD) between intervention and control groups for randomized controlled trials (RCTs). Between study heterogeneity was estimated using Cochran's Q and the I 2-inconsistency index. Internal validity of included randomized trials was determined with the Cochrane Collaboration's tool for assessing the risk of bias. RESULTS: Twenty-three articles were included for qualitative and 11 articles for quantitative synthesis. Meta-analysis of 14 RCTs (nine articles) indicated a positive short-term (postprandial) effect of coffee intake on flow-mediated dilation (FMD) as a measure of EF (WMD: 1.93%[95% CI: 1.10-2.75]; I 2= 97.9%). Meta-analysis of three long-term RCTs(two articles) found no such effect on FMD (WMD: -0.08% [-3.82 to 3.66]; I 2= 61.4%).Most short-term information was from studies at low or unclear risk of bias, while the proportion of long-term information from studies at high risk of bias was considerable. CONCLUSION: The results from this meta-analysis suggest a beneficial short-term effect of coffee intake on EF as measured by FMD. However, there might be unfavorable effects on AS. Our findings must be interpreted cautiously as the number of studies were low and included studies had a considerable risk of bias.

Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.

Effects of Melissa officinalis (Lemon Balm) on cardio-metabolic outcomes: A systematic review and meta-analysis.

Recent evidence indicates a beneficial effect of Melissa officinalis (MO) intake on several chronic diseases. However, the effects of MO intake have not yet been systematically reviewed. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of MO intake and focused on several cardiometabolic outcomes. MEDLINE, Scopus, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials were searched for MO-RCTs evaluating cardiometabolic outcomes. Random-effects meta-analyses estimated the pooled standardized mean differences (SMD) between intervention and control groups. Risk of bias was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in RCTs. Seven RCTs were finally deemed eligible. MO intake was associated with a reduced total cholesterol (TC) (SMD: -0.26; 95% CI: -0.52, -0.01; I2 = 13.7%; k = 6) and a reduced systolic blood pressure (SBP) (SMD: -0.56; 95% CI: -0.85, -0.27; I2 = 00.0%; k = 3). MO intake was not associated with statistically significant changes in triglycerides, low-density lipoprotein, diastolic blood pressure, high sensitivity c-reactive protein levels, fasting blood sugar, HbA1c, insulin or high-density lipoprotein levels. No serious adverse events were reported. The risk of bias was high in a considerable amount of studies. Our study suggests that MO is a safe supplement with beneficial effects on TC and SBP. However, the findings of our study must be seen in the light of major limitations such as a low number of included studies and a serious risk of bias. High-quality RCTs are needed for firm conclusions concerning the effects of MO on cardiometabolic outcomes.

Pitfalls in meta-analysis.

Systematic reviews with meta-analyses are powerful instruments to synthesize research. If done correctly, they may constitute the highest level of evidence by combining several individual studies. As high-quality evidence is scarce in the field of complementary medicine, meta-analyses of randomized trials may shed new light on both efficacy and safety, but they must be properly conducted. In this commentary to a recently published paper we elaborate on methodological pitfalls in meta-analysis that every researcher should avoid to gain true high-quality evidence.