Background: Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested. Objectives: This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia. Results: The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia). Conclusion: The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.

MicroRNA (miRNA) regulate post-transcriptionally the expression of osteogenesis and angiogenesis associated genes and emerge as potential non-invasive biomarkers in vascular and bone diseases. Severe abdominal aortic calcification (AAC) is associated with higher risk of cardiovascular event and of fragility fracture. To identify miRNA linked to the aggravation of AAC and to incident osteoporotic fracture. Postmenopausal women (>50 years) with available serum at inclusion and data for each outcome (Kauppila score and incident fracture) were selected from the OFELY prospective cohort. We conducted a case-control study in 434 age-matched women, 50% with incident osteoporotic fracture over 20 years of follow-up and a second study in 183 women to explore AAC over 17 years. Serum expression of three miRNA involved in vascular calcification and bone turnover regulation (miRs-26a-5p,-34a-5p, and -223-5p) was quantified at baseline by TaqMan Advanced miRNA technology and expressed by relative quantification. Outcomes were the association of miRNA levels with (1) incident osteoporotic fractures during 20 years, (2) AAC aggravation during 17 years. MiRNA level was not associated with incident fractures (miR-26a-5p: 1.06 vs 0.99, p = 0.07; miR-34a-5p: 1.15 vs 1.26, p = 0.35; miR-223a-5p: 1.01 vs 1.05, p = 0.32). 93 women had an increase in Kauppila score over 17 years while 90 did not. None of the miRNAs was associated with an aggravation in AAC (miR-26a-5p: 1.09 vs 1.10, p = 0.95; miR-34a-5p: 0.78 vs 0.73, p = 0.90; miR-223-5p: 0.97 vs 0.78, p = 0.11). Circulating miR-26a-5p, -34a-5p and -223-5p are not significantly associated with incident fracture and AAC aggravation.

Magnesium (Mg) is a pivotal and very complex component of healthy aging in the cardiovascular-muscle-bone triad. Low Mg levels and low Mg intake are common in the general aging population and are associated with poorer outcomes than higher levels, including vascular calcification, endothelial dysfunction, osteoporosis, or muscle dysfunction/sarcopenia. While Mg supplementation appears to reverse these processes and benefit the triad, more randomized clinical trials are needed. These will allow improvement of preventive and curative strategies and propose guidelines regarding the pharmaceutical forms and the dosages and durations of treatment in order to optimize and adapt Mg prescription for healthy aging and for older vulnerable persons with comorbidities.

Advantages and disadvantages of intermittent versus daily vitamin D supplementation especially in adults with or at risk of osteoporosis are discussed by the Osteoporosis Research and Information Group (GRIO). The analysis of the literature suggests that intermittent long-term high doses vitamin D supplementation (such as 60,000IU/month or more), may increase the risk of falls, fracture and premature death in certain populations, while daily doses of 800-1000IU with calcium decrease falls and non-vertebral fractures in the elderly with vitamin D deficiency. In patients with or at risk of osteoporosis we hence recommend measuring the 25(OH)D concentration prior to supplementation and to provide vitamin D supplementation (with optimization of calcium intake if needed) to obtain a concentration between 30 and 60ng/mL. We recommend the use of an initial loading dose, especially in those who need a quick repletion of vitamin D store (symptoms of osteomalacia and/or 25(OH)D concentration <12ng/mL, patients eligible for treatment with potent antiresorptive therapy), followed by a maintenance dose. A daily supplementation should be the rule when possible. When daily forms are however not available or not reimbursed, we recommend, like other experts, to continue using intermittent dosing with the smallest available dose (≤50,000IU) and the shortest interval between doses as a stopgap until reimbursement or adequate daily pharmaceutical forms (pills or soft capsules of 1000, 2000IU) are available.