The Effects of Acute and Chronic Alcohol Administration and Withdrawal on Bone Microstructure, Mechanical Strength, and Remodeling Protein Expression and Their Relation to an Antioxidant and FGF23 In Vivo.

Alcohol's detrimental effects on bone health are well established, yet some literature suggests moderate consumption may offer benefits. With alcohol use on the rise, we investigate the impact of acute and chronic alcohol administration, along with withdrawal, on male Wistar rat femurs. We observed a transient cortical thickness increase with acute alcohol (AA) compared to chronic exposure (CA) but no significant changes in trabecular parameters or mechanical properties. High osteocalcin and osteopontin expression levels were noted in AA, alongside elevated RANKL expression. Conversely, CA showed low TRAP levels. FGF23 expression significantly increased during alcohol withdrawal (AW), while GPX decreased after chronic exposure but rose during withdrawal. Although mechanical strength changes were insignificant, biochemical shifts suggest alcohol exposure promotes bone resorption, reduces antioxidant protection, and potentially hampers active vitamin D and phosphate reabsorption via FGF23 upregulation.

Effects of E'Jiao on Skeletal Mineralisation, Osteocyte and WNT Signalling Inhibitors in Ovariectomised Rats.

E'Jiao is a traditional Chinese medicine derived from donkey skin. E'Jiao is reported to suppress elevated bone remodelling in ovariectomised rats but its mechanism of action is not known. To bridge this research gap, the current study aims to investigate the effects of E'Jiao on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. Female Sprague-Dawley rats (3 months old) were ovariectomised and supplemented with E'Jiao at 0.26 g/kg, 0.53 g/kg and 1.06 g/kg, or 1% calcium carbonate (w/v) in drinking water. The rats were euthanised after two months of supplementation and their bones were collected for Fourier-transform infrared spectroscopy, histomorphometry and protein analysis. Neither ovariectomy nor treatment affected the skeletal mineral/matrix ratio, osteocyte number, empty lacunar number, and Dickkopf-1 and sclerostin protein levels (p > 0.05). Rats treated with calcium carbonate had a higher Dickkopf-1 level than baseline (p = 0.002) and E'Jiao at 0.53 g/kg (p = 0.002). In conclusion, E'Jiao has no significant effect on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. The skeletal effect of E'Jiao might not be mediated through osteocytes.

A Mini Review on Osteoporosis: From Biology to Pharmacological Management of Bone Loss.

Osteoporosis refers to excessive bone loss as reflected by the deterioration of bone mass and microarchitecture, which compromises bone strength. It is a complex multifactorial endocrine disease. Its pathogenesis relies on the presence of several endogenous and exogenous risk factors, which skew the physiological bone remodelling to a more catabolic process that results in net bone loss. This review aims to provide an overview of osteoporosis from its biology, epidemiology and clinical aspects (detection and pharmacological management). The review will serve as an updated reference for readers to understand the basics of osteoporosis and take action to prevent and manage this disease.

Reduction in Absolute Neutrophil Counts in Patient on Clozapine Infected with COVID-19.

Despite its severe adverse effects, such as agranulocytosis, clozapine is the primary treatment for treatment-resistant schizophrenia. The established clozapine monitoring system has contributed to reducing agranulocytosis incidence and mortality rates. However, the pandemic coronavirus disease 2019 (COVID-19) has caused changes in the monitoring system. This review aimed to assess the current evidence on the neutrophil changes in the patient on clozapine treatment and infected with COVID-19. Individual cases reported various absolute neutrophil count (ANC) levels, normal, reduced, or elevated. No agranulocytosis case was reported. One case had a borderline moderate-severe ANC level, but the patient was in the 18-week period of clozapine treatment. A cumulative analysis of case the series initially reported inconclusive results. However, a more recent study with a larger sample size reported a significant reduction in the ANC during COVID-19 infection. Nevertheless, this effect is transient as no significant difference was found between the baseline and the post-infection period in ANC levels. In conclusion, COVID-19 is associated with a temporary reduction in ANC levels. The results supported the recommendation to reduce the frequency of clozapine monitoring in the eligible candidates. However, more data are required to confirm the current findings given the limitations, including study design, sample size, and statistical analysis.

Treatments of Sexual Dysfunction in Opioid Substitution Therapy Patients: A Systematic Review and Meta-Analysis.

Sexual dysfunction is a common condition in the opioid substitution therapy (OST) population. We aimed to determine the efficacy and safety of treatment for sexual dysfunction in the OST population. We searched for interventional studies from Medline, PubMed, and Scopus. Three independent authors conducted a risk-of-bias assessment (RoB 2). A total of seven studies (five randomized-controlled trials, two quasi-experimental), including 473 patients with sexual dysfunction, were identified. Among these, three bupropion (n=207), one trazodone (n=75), two rosa Damascena (n=100), and one ginseng (n=91) studies had reported significantly improve various sexual functioning domains in both genders. In a meta-analysis, bupropion significantly increased male sexual function with standardized mean difference of 0.53; 95% confidence interval of 0.19-0.88; P < 0.01; I2=0. The adverse effects were minor for all agents, and no significant difference between treatment and placebo groups in randomized-controlled trials. These agents have a promising future as therapy for sexual dysfunction in the OST population. However, given the limited sample size and number of studies, further studies should be conducted to confirm the use of these agents.

Factors Associated with Low Bone Density in Opioid Substitution Therapy Patients: A Systematic Review.

Background: Long-term opioid therapy is a risk factor for low bone mineral density (BMD). However, other factors may also contribute to low BMD. Several studies have examined the variables that might contribute to low BMD in patients receiving opioid replacement therapy (OST). However, to our knowledge, there was no systemic review conducted to address this particular issue. Thus, we reviewed the articles on the factors associated with low BMD in the population of opioid use disorder receiving substitution therapy. Methods: The articles that examined correlates or risk factors of low BMD in OST population were retrieved from OVID, SCOPUS, and PUBMED from inception until July 2020 by two independent investigators. Results: A total of 429 articles from three databases were retrieved initially. After screening based on eligibility criteria, five articles were included in the final analysis. The risk factors or correlates found to be significantly associated with low BMD in the OST population include male gender, low body mass index, low testosterone level, methadone or heroin use, and longer duration of heavy alcohol use. The review limitations include small sample sizes and inconsistent definition of variables. Conclusion: OST patients should be screened for BMD and its associated factors. Guidelines and training of practitioners involving in the OST service should be provided to increase the detection of low BMD in the OST population.