Brief overview: Current evidence suggests vitamin D replacement may reduce risk for acute respiratory tract infections (ARTI) in people with deficiency or insufficiency, although the effects of supplementation on incidence and severity of ARTI in the general population remain unknown. Oral vitamin D supplemzentation taken at routine doses appears to be generally safe and well tolerated. Verdict: Current experimental evidence remains inconclusive regarding the effects of vitamin D supplementation in the general population for the prevention and treatment of acute respiratory tract infections (ARTI). There is also insufficient evidence to draw conclusions regarding the impact of vitamin D supplementation on the severity or duration of ARTI, nor on outcomes related to lung injury or hospitalization from ARTI. Based on this rapid review, sources of significant heterogeneity in published clinical trials include: differences study populations, inconsistent assessment of serum status at baseline, dosing variability, varying routes of administration, and/or inconsistent definitions of outcome measures. Experimental evidence and observations in large cohorts are generally consistent that vitamin D deficiency (<50 nmol/L [<20 ng/mL]) and insufficiency (<75 nmol/L [<30 ng/mL]) of serum 25-hydroxycholecalciferol (25-OHD) concentration is associated with increased risk of ARTI, and supplementation for those with deficiency/insufficiency may lead to clinically meaningful reductions in the incidence of ARTI. In this rapid review, vitamin D was primarily administered as oral supplementation, and findings suggested significant differences in daily oral dosing compared to periodic bolus dosing. Based on the available experimental evidence, vitamin D supplementation appears to have a high margin of safety with very few adverse events reported in children or adults from a variety of dosing strategies. Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. The available mechanistic evidence related to immunological requirements for adequate vitamin D, the availability of observational and experimental evidence suggestive of clinically meaningful benefits (especially in deficient/insufficient participants), and the high margin of safety, should make vitamin D a high priority for additional clinical research during the current COVID-19 pandemic.
Chronic kidney disease-mineral and bone disorder is prevalent. There is controversy regarding whether calcium-based phosphate binders or sevelamer - a non-calcium phosphate binder constitute a better therapeutic alternative. Searching in Epistemonikos database, which is maintained by screening multiple information sources, we identified 12 systematic reviews comprising 61 studies of which 41 correspond to randomized trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded sevelamer may decrease hypercalcemia, but with a higher incidence of gastrointestinal effects than calcium based phosphate binders. It is unclear if there are differences in mortality because the certainty of the evidence is very low.
The 2010 clinical practice guideline for the diagnosis and management of osteoporosis in Canada1 focused on the care of adults living in the community. However, the fracture rate for adults living in long-term care (residents) is two to four times that of adults of similar age living in the community, and one-third of older adults who experience hip fracture are residents in long-term care.2 Hip fracture is one of the most serious consequences of osteoporosis and also one of the leading causes of admission to hospital.3 When residents return to long-term care after a hospital stay, they need additional hours of specialized care.4,5 In addition, fracture pain and delirium frequently associated with analgesia are distressing for residents and their families. Vertebral fractures are also a concern for residents, and the reported prevalence is up to 30% (for at least one moderate to severe fracture).6 Multiple vertebral fractures can be a substantial cause of pain, anxiety, depression, reduced pulmonary function7 and agitation.
Frail older adults at high risk of fracture in long-term care face other challenges. More than 40% have dementia,8 a similar percentage experience swallowing difficulties,9,10 and over 20% may have renal insufficiency.11,12
It may be difficult to identify residents at high risk of fracture, as the current fracture risk assessment tools (the Canadian Association of Radiologists and Osteoporosis Canada tool13 [CAROC; www.osteoporosis.ca/multimedia/pdf/CAROC.pdf] and the Canadian WHO Fracture Risk Assessment Tool [FRAX; www.shef.ac.uk/FRAX/]) provide 10-year fracture risk and have not been validated in long-term care, where over 20% of residents may die within one year of admission.14,15 Most research regarding risk assessment and pharmacologic therapies has not included those with multiple comorbidities.16,17
OBJECTIVE: To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes.
DESIGN: Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation.
DATA SOURCES: Medline, Embase, and screening of citations and references.
ELIGIBILITY CRITERIA: Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D).
RESULTS: 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.
CONCLUSIONS: Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.
Brief overview: Current evidence suggests vitamin D replacement may reduce risk for acute respiratory tract infections (ARTI) in people with deficiency or insufficiency, although the effects of supplementation on incidence and severity of ARTI in the general population remain unknown. Oral vitamin D supplemzentation taken at routine doses appears to be generally safe and well tolerated. Verdict: Current experimental evidence remains inconclusive regarding the effects of vitamin D supplementation in the general population for the prevention and treatment of acute respiratory tract infections (ARTI). There is also insufficient evidence to draw conclusions regarding the impact of vitamin D supplementation on the severity or duration of ARTI, nor on outcomes related to lung injury or hospitalization from ARTI. Based on this rapid review, sources of significant heterogeneity in published clinical trials include: differences study populations, inconsistent assessment of serum status at baseline, dosing variability, varying routes of administration, and/or inconsistent definitions of outcome measures. Experimental evidence and observations in large cohorts are generally consistent that vitamin D deficiency (<50 nmol/L [<20 ng/mL]) and insufficiency (<75 nmol/L [<30 ng/mL]) of serum 25-hydroxycholecalciferol (25-OHD) concentration is associated with increased risk of ARTI, and supplementation for those with deficiency/insufficiency may lead to clinically meaningful reductions in the incidence of ARTI. In this rapid review, vitamin D was primarily administered as oral supplementation, and findings suggested significant differences in daily oral dosing compared to periodic bolus dosing. Based on the available experimental evidence, vitamin D supplementation appears to have a high margin of safety with very few adverse events reported in children or adults from a variety of dosing strategies. Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. The available mechanistic evidence related to immunological requirements for adequate vitamin D, the availability of observational and experimental evidence suggestive of clinically meaningful benefits (especially in deficient/insufficient participants), and the high margin of safety, should make vitamin D a high priority for additional clinical research during the current COVID-19 pandemic.
