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Objectives: Studies suggest that melatonin may promote cardiovascular protection. Previous trials have primarily been performed on co-morbid patients. Little information exist on the effect in postmenopausal women with general good health. Design, participants and intervention: In a double-blinded placebo-controlled study, we randomized 41 postmenopausal women to either 10 mg melatonin per day or placebo for 3 months. Outcome measures: Outcomes of the trial was changes in blood pressure, pulse wave velocity (PWV), and quality of sleep evaluated by Pittsburgh Sleep Quality Index (PSQI). Results: Thirty-nine women completed the study. Mean age was 63 years (range 55–75 years). Over the 3 months of the trial, PWV did not differ between groups: Placebo 1.1% (IQR −2.1;9.9) vs. melatonin 0.0% (IQR-9.8;4.1), p = 0.43). The were no significant differences in blood pressure bewteen melatonin and placebo group. Both groups had a pour quality of sleep at baseline (placebo: PSQI 6.0 (IQR 3.3; 8.8) vs. melatonin PSQI 6.0 (IQR 3.0; 10.0), p = 0.94), which did not change in response to treatment. Conclusion: In healthy postmenopausal women, supplementation with 10 mg melatonin was well-tolerated, but we did not observe any significant improvements in pulse wave velocity, blood pressure or quality of sleep compared with placebo.

Background: Prior studies of the pharmacogenomics of osteonecrosis of the jaw (ONJ) have had various methodological limitations, including using candidate gene selection as their sole strategy, a small number of ONJ cases, or a study population based on an oncology setting. Objectives: The aim of our case-control study was to evaluate previously reported associations between genetic factors and ONJ, which were based on either genome-wide association studies (GWAS) or candidate gene approaches. Furthermore, we aimed to identify genetic risk factors for ONJ by using GWAS to determine single-nucleotide polymorphisms (SNPs) with statistically significant differences in frequency between ONJ patients and osteoporosis controls. Methods: Patients with medically confirmed ONJ and who were registered in the Scandinavian Cohort of ONJ patients were included. Controls from the general population were matched on age (±5 years), sex, and cumulative antiresorptive drug exposure. The ONJ diagnosis date for cases corresponded to the index date for matched controls. DNA isolation, genotyping, and data analyses were performed by Q2/EA Genomics using standard protocols and best practices. Blood or tissue samples for 55 ONJ cases and 125 controls were collected. Due to the low quality of the tissue samples, final analyses were based on blood samples of 40 ONJ cases and 124 controls. Results: We detected no significant genome-wide associations. Of the 43 SNPs with ONJ association in prior studies, none were replicated in our study. Conclusions: Even though our study sample is the largest to date, we had limited statistical power for GWAS but adequate power for replication analyses. Our study provides no evidence for any genetic predisposition to ONJ. Future studies could increase their statistical power by combining ONJ GWAS datasets and by performing a meta-analysis or pursuing a sequencing strategy in order to identify rare variants.

Introduction: Low levels of sex hormones are common in patients with chronic kidney disease (CKD) and may be a contributing factor to bone fragility. We investigated associations between levels of sex hormones and bone mineral density (BMD) in adult kidney transplantation candidates. Methods: Volumetric BMD of spine and hip were measured by computed tomography. Parathyroid hormone (PTH), testosterone (T), estradiol (E), and sex hormone–binding globulin were measured from fasting morning blood samples. Bioavailable (Bio) T and E were calculated based on constants for protein binding. Results: A total of 146 patients (102 men and 44 women) were included in the analyses. The median age was 54 years (range, 32−72 years); 32% were diabetic; and 36% received maintenance dialysis therapy. In men, Bio T was positively associated with BMD at the lumbar spine (β = 5.02, P = 0.002), total hip (β = 6.35, P = 0.001), and femoral neck (β = 13.9, P = 0.002), independently of age, body mass index, dialysis, diabetes type 1 and 2, parathyroid hormone, and steroid exposure. Bio E was positively associated with BMD at the lumbar spine (β = 0.23, P = 0.03) and femoral neck (β = 0.61, P = 0.04) using the same fully adjusted model. In postmenopausal women, Bio T was positively correlated with lumbar spine BMD (r = 0.46, P = 0.02). Conclusion: High endogenous levels of sex hormones are associated with greater BMD in male kidney transplantation candidates. Disturbances in the gonadal axis may contribute to skeletal fragility in men with late-stage CKD. Keywords: bone density, chronic kidney disease, gonadal sex steroids, hypogonadism, osteoporosis