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• W2912245472 abstract "Mark Bolland and colleagues1Bolland MJ Grey A Avenell A Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis.Lancet Diabetes Endocrinol. 2018; 6: 847-858Summary Full Text Full Text PDF PubMed Scopus (247) Google Scholar identified 81 open-label and blinded randomised trials with 53 537 adult participants that compared vitamin D with untreated controls, placebo, or another dose of vitamin D. The authors report no effect of vitamin D supplementation on fractures and falls. They also report no benefit for bone mineral density given their subjectively defined futility boundary of 0·5% improvement. Notably, in three of five skeletal locations, the benefits of vitamin D on bone mineral density were significant, with increases of 0·34% (95% CI 0·13–0·55) at the total hip, 0·76% at the femoral neck (0·42–1·09), and 0·25% (0–0·49) at the lumbar spine. Bolland and colleagues also excluded a substantial portion of the literature on vitamin D from their meta-analysis, namely all trials that combined vitamin D with calcium and compared with placebo. Such trials constitute about 40% of the high-quality data on fracture reduction and have contributed to the current guidelines recommending 800 IU vitamin D daily. The extent of this bias is documented by a 2016 meta-analysis2Weaver CM Alexander DD Boushey CJ et al.Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.Osteoporos Int. 2016; 27: 367-376Crossref PubMed Scopus (315) Google Scholar that summarised eight randomised clinical trials (n=30 970 participants) that were not considered by Bolland and colleagues. That meta-analysis showed a significant reduction in risk of total fractures (relative risk [RR] 0·85, 95% CI 0·73–0·98) and a significant reduction in hip fractures (0·70, 0·56–0·87).2Weaver CM Alexander DD Boushey CJ et al.Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.Osteoporos Int. 2016; 27: 367-376Crossref PubMed Scopus (315) Google Scholar Furthermore, previous meta-analyses and international guidelines for older adults (aged ≥65 years) support a daily dose of 800–1000 IU vitamin D, and lower doses are considered ineffective.3Bischoff-Ferrari HA Orav EJ Willett WC et al.A pooled analysis of vitamin D dose requirements for fracture prevention.N Engl J Med. 2012; 367: 40-49Crossref PubMed Scopus (613) Google Scholar, 4Foundation IO Guideline on Vitamin D.https://www.iofbonehealth.org/new-vitamin-d-recommendations-older-men-and-womenDate accessed: October 17, 2018Google Scholar Additionally, large annual bolus doses of vitamin D have consistently increased the risk of falls and fractures.5Sanders KM Stuart AL Williamson EJ et al.Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.JAMA. 2010; 303: 1815-1822Crossref PubMed Scopus (1081) Google Scholar, 6Smith H Anderson F Raphael H Maslin P Crozier S Cooper C Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population-based, randomized, double-blind, placebo-controlled trial.Rheumatology (Oxford). 2007; 46: 1852-1857Crossref PubMed Scopus (306) Google Scholar Our re-analysis of eight randomised, placebo-controlled trials for total fractures and 11 for falls (that tested 800–1000 IU vitamin D daily with more than 50% adherence, and excluding the large annual dosing trials), all of which were among those analysed by Bolland and colleagues, suggests a significant reduction in total fractures (RR 0·86, 95% CI 0·75–0·98) and a significant reduction in falls (0·88, 0·81–0·95; appendix). In conclusion, we disagree with Bolland and colleagues and suggest that their selection of studies is biased for the reasons stated above. In view of the small risk and cost, we believe that it is essential not to discourage older adults from receiving 800–1000 IU vitamin D daily, and to further study the optimal dose and application of vitamin D. Clinical decisions should also consider other health outcomes in addition to fractures and falls, as explored in the recently published VITAL trial7Manson JE Cook MR Lee IM et al.Vitamin D supplements and prevention of cancer and cardiovascular disease.N Engl J Med. 2018; (published online Nov 10.)DOI:10.1056/NEJMoa1809944Google Scholar and the soon to be published DO-HEALTH trial (NCT01745263). HAB-F reports grants from DSM Nutritional Products, grants from Pfizer and Wild, and personal fees from Roche-Diagnostics, MedaPharma, and Nestlé, outside the submitted work. BD-H reports grants from DSM Nutritional Products, and grants and personal fees from Pfizer, outside the submitted work. EJO, LA, and WCW declare no competing interests. Download .pdf (.24 MB) Help with pdf files Supplementary appendix Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysisOur findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines. Full-Text PDF Vitamin D supplementation and musculoskeletal health – Authors' replyHeike Bischoff-Ferrari and colleagues are concerned that, in our meta-analysis and trial sequential analysis of vitamin D supplementation for musculoskeletal health in adults,1 we concluded that statistically significant effects of vitamin D supplements on bone density were not clinically important. However, differences (compared with controls) of −0·16% to 0·76% that do not progressively increase over 1–5 years are smaller than the average loss of bone density in post-menopausal women of 0·5–1·0% over one year,2 and so are clinically irrelevant. Full-Text PDF Vitamin D supplementation and musculoskeletal healthProtective effects of vitamin D supplementation against non-musculoskeletal outcomes, such as acute respiratory infection, are strongest in people with baseline 25-hydroxyvitamin D (25OHD) concentrations less than 25 nmol/L.1 It would seem reasonable to expect a similar phenomenon to apply to the musculoskeletal outcomes investigated in the meta-analysis of aggregate data by Mark Bolland and colleagues.2 Unfortunately, methodological problems—including a lack of access to individual participant data—limit the ability of this analysis to determine whether effects of vitamin D supplementation vary according to baseline 25OHD concentration. Full-Text PDF Vitamin D supplementation and musculoskeletal healthIn their meta-analysis1 of randomised clinical trials (RCTs) assessing the effects of vitamin D supplementation on fractures, falls, and bone mineral density in people older than 18 years, Mark Bolland and colleagues reported that vitamin D supplementation did not prevent falls or fractures in this age group. However, their approach to evaluating such RCTs might not have been sufficiently comprehensive. Full-Text PDF Vitamin D supplementation and musculoskeletal healthMark Bolland and colleagues1 conclude that vitamin D supplementation is futile as a therapeutic agent to prevent falls and fractures. Many physicians and patients might thus conclude that they can stop prescribing or taking vitamin D supplements, which is a potentially dangerous message given the prevalence of vitamin D deficiency worldwide. Full-Text PDF" @default.
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