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      Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group

      review-article
      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 17 , 5 , 6 , 11 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 1
      Aging Clinical and Experimental Research
      Springer International Publishing
      Vitamin D, Fragility fracture, Falls, Osteoarthritis

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          Abstract

          Vitamin D is a key component for optimal growth and for calcium–phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

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          Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

          The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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            Interventions for preventing falls in older people living in the community

            Cochrane Database of Systematic Reviews
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              Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.

              Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor. To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008. 500,000 IU of cholecalciferol or placebo. Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels. Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing. Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures. anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.
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                Author and article information

                Contributors
                Thierry.chevalley@hcuge.ch
                Journal
                Aging Clin Exp Res
                Aging Clin Exp Res
                Aging Clinical and Experimental Research
                Springer International Publishing (Cham )
                1594-0667
                1720-8319
                26 October 2022
                26 October 2022
                : 1-21
                Affiliations
                [1 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Service of Bone Diseases, , Geneva University Hospitals and Faculty of Medicine, ; Geneva, Switzerland
                [2 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, , University of Florence, ; Florence, Italy
                [3 ]GRID grid.7872.a, ISNI 0000000123318773, Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, , University College Cork, ; Cork, Ireland
                [4 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Department of Clinical Chemistry, , University of Liege, CHU de Liege, ; Liege, Belgium
                [5 ]GRID grid.5491.9, ISNI 0000 0004 1936 9297, MRC Lifecourse Epidemiology Centre, , University of Southampton, ; Southampton, UK
                [6 ]GRID grid.430506.4, ISNI 0000 0004 0465 4079, NIHR Southampton Biomedical Research Centre, , University of Southampton and University Hospital Southampton NHS Foundation Trust, ; Southampton, UK
                [7 ]CNR Aging Branch-IN, Padua, Italy
                [8 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, UKNIHR Oxford Biomedical Research Centre, , University of Oxford, ; Oxford, UK
                [9 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Chair for Biomarkers of Chronic Diseases, Biochemistry Department, , College of Science King Saud University, ; Riyadh, 11451 Saudi Arabia
                [10 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of Osteoporosis, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland
                [11 ]International Osteoporosis Foundation, Nyon, Switzerland
                [12 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Division of Public Health, Epidemiology and Health Economics, WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing, , University of Liège, ; Liege, Belgium
                [13 ]GRID grid.9983.b, ISNI 0000 0001 2181 4263, Centro de Estudos Egas Moniz Faculdade de Medicina da Universidade de Lisboa, ; Lisbon, Portugal
                [14 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, Department of Rheumatology, , University of Lille, CHU Lille, MABlab ULR 4490, ; Lille, France
                [15 ]GRID grid.411347.4, ISNI 0000 0000 9248 5770, Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS), ; Madrid, Spain
                [16 ]Dipartimento dei percorsi geriatrici della fragilità, Geriatria, Accettazione geriatrica e Centro di ricerca per l’invecchiamentodella continuità di cura e riabilitativi, IRCCS INRCA, Ancona, Italy
                [17 ]GRID grid.508992.f, ISNI 0000 0004 0601 7786, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, ; Boston, MA USA
                [18 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, Centre for Metabolic Bone Diseases, , University of Sheffield Medical School, ; Sheffield, UK
                [19 ]GRID grid.411958.0, ISNI 0000 0001 2194 1270, Mary McKillop Institute for Health Research, , Australian Catholic University, ; Melbourne, Australia
                [20 ]GRID grid.410566.0, ISNI 0000 0004 0626 3303, Department of Endocrinology, , Ghent University Hospital, ; Ghent, Belgium
                [21 ]GRID grid.8515.9, ISNI 0000 0001 0423 4662, Bone Unit, , Lausanne University Hospital and University of Lausanne, ; Lausanne, Switzerland
                [22 ]Scientific Office, Federal Office for Safety in Health Care, Austrian Medicines and Medical Devices Agency, Vienna, Austria
                [23 ]GRID grid.443875.9, ISNI 0000 0001 2237 4036, Spanish Agency for Medicines and Medical Devices, ; Madrid, Spain
                [24 ]GRID grid.411374.4, ISNI 0000 0000 8607 6858, Department of Clinical Pharmacology Diabetes, Nutrition and Metabolic Disorders, , CHU Liege, ; Liège, Belgium
                [25 ]GRID grid.3575.4, ISNI 0000000121633745, Ageing and Health Unit, Department of Maternal, Newborn, Child and Adolescent Health & Ageing, , WHO HQ, ; Geneva, Switzerland
                [26 ]GRID grid.25697.3f, ISNI 0000 0001 2172 4233, Department of Rheumatology, North Hospital, CHU Saint-Etienne and INSERM U1059, , University of Lyon-University Jean Monnet, ; Saint-Etienne, France
                [27 ]GRID grid.10776.37, ISNI 0000 0004 1762 5517, Geriatric Unit, Department of Internal Medicine and Geriatrics, , University of Palermo, ; Palermo, Italy
                [28 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Department of Medical Humanities, , Amsterdam University Medical Centre, ; Amsterdam, The Netherlands
                [29 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Department of Public Health, Epidemiology and Health Economics, , University of Liège, ; Liège, Belgium
                Author information
                http://orcid.org/0000-0003-3338-1148
                http://orcid.org/0000-0003-3684-2376
                Article
                2279
                10.1007/s40520-022-02279-6
                9607746
                36287325
                f4d423ce-5455-44be-8ef9-6f893dfb7861
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 September 2022
                : 10 October 2022
                Funding
                Funded by: University of Geneva
                Categories
                Review Article

                vitamin d,fragility fracture,falls,osteoarthritis
                vitamin d, fragility fracture, falls, osteoarthritis

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