Elsevier

Autoimmunity Reviews

Volume 9, Issue 11, September 2010, Pages 709-715
Autoimmunity Reviews

Review
Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice

https://doi.org/10.1016/j.autrev.2010.06.009Get rights and content

Abstract

Background

There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations.

Methods

Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale.

Results and conclusion

Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care.

A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D2 and 25(OH)D3 is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing.

Introduction

Once thought to have consequences only for bone health, vitamin D deficiency has been associated with a large number of conditions such as cancer, autoimmune disease, and cardiovascular disease. A large part of the population does not meet vitamin D requirements because vitamin D is mainly synthesized when the skin is exposed to ultraviolet (UV) B radiation and contemporary life is associated with reduced sun exposure (we expose less than 5% of our skin to the sun) and use of UVB-blocking sunscreens [1]. Dark-skinned individuals require more sun exposure to have the same vitamin D production as people with less skin pigmentation, and the same is true for older versus younger individuals [2]. Dietary sources of vitamin D3 (cholecalciferol) are few and only significant in oily fish. Vitamin D2 (ergocalciferol), the plant/mushroom form of vitamin D, is almost absent in the diet. Supplementation with vitamin D can be done either with vitamin D2 or vitamin D3 but availability of these two forms greatly differs between countries. The optimal serum level of 25-hydroxyvitamin D (25(OH)D)—the primary circulating form of vitamin D—needed for optimal health is unknown. However, a recent benefit–risk assessment of vitamin D suggested that it may be similar or possibly higher than needed for optimal bone health and calcium metabolism [3].

The abundance of publications on vitamin D (PubMed search: 2844 in 2000–2001 increasing to 4635 in 2008–2009), differing in level of evidence and consequences for clinical practice, hinders the physician in assessing the importance of vitamin D status for a specific patient. Therefore, a 2-day Vitamin D Summit Meeting was held on 7–8 November 2009 in Paris, with the goal of translating current evidence from clinical, experimental and epidemiological studies into recommendations for everyday clinical practice. The recommendations are intended to be used in clinical practice and concern adult patients with, or individuals at risk for, classical applications of vitamin D such as osteoporosis, chronic kidney disease (CKD), and endocrinopathies. On the other hand the recommendations apply to adult patients with, or individuals at least 18 years old at risk for, diseases in which the role of vitamin D is emerging such as cardiovascular and autoimmune diseases and cancer. Therefore, a multidisciplinary group of 25 experts, from 12 different countries, addressed the following questions with regard to the described population:

  • Who should be tested for vitamin D deficiency?

  • What is the recommended range of serum 25(OH)D?

  • Who should be supplemented?

  • When should the testing be performed?

This perspective differs from, and could result in another set of standards than policy documents intended for the community at large (e.g. Institute of Medicine [4] and Standing Committee of European Doctors [5]). Until the results of long-term large scale randomized controlled trials (RCTs) in the emerging fields are available, the recommendations presented in this paper should not be extrapolated to the general healthy population.

The chairpersons of the meeting (MP, JCS, JJB, JL, YS, and TW), all experts in the field, defined the format of the meeting and warranted that the participants consisted of experts on vitamin D in different clinical specialties. The meeting started with a plenary session in which the state of the art was outlined from different perspectives and disciplines. Afterwards, the most important literature referring to a disease area was discussed in group sessions per specialty and translated into recommendations for each specialty. The recommendations were then presented and discussed during a plenary session.

The paper, consisting of a brief summary of the most important evidence and recommendations for clinical practice, based on the literature review and the experience of the authors, was drafted by the chairpersons. The draft was reviewed by all panel members and a scoring system was applied to measure agreement for each of the recommendations.

Section snippets

Classical clinical effects of vitamin D

Vitamin D has an impact on bone density and bone quality. In addition, by increasing muscle strength, adequate vitamin D status reduces the risk of falling in older individuals. Therefore, vitamin D has a dual benefit for prevention of fractures in the elderly, a benefit on bone density and muscle strength. To determine the anti-fracture efficacy of oral vitamin D supplementation in individuals ≥ 65 years old, Bischoff-Ferrari et al. did a meta-analysis of 12 double-blind RCTs for non-vertebral

Recommendations of the expert panel

The authors acknowledged the lack of adequate RCT data in the non-musculoskeletal disease areas and the fact that most RCTs were performed in older individuals, but they formulated recommendations based on the available evidence, risk–benefit considerations and clinical experience. All recommendations were individually scored using an agreement index ranging from 1 (not agree at all) to 5 (fully agree). The mean score is presented in the text next to each recommendation.

Conclusions

The role of vitamin D in maintaining normal calcium–phosphorus homeostasis is well-established. Vitamin D deficiency leads to rickets in children and osteomalacia in adults, and long-term deficiency contributes to osteoporosis. More recently, vitamin D deficiency has been associated with other chronic conditions, including cardiovascular disease, autoimmune disease, and cancer. The current recommendations address vitamin D supplementation, testing and monitoring in individuals with or at risk

Take-home messages

  • The 25(OH)D level in specific groups of patients with or at risk for musculoskeletal health problems, cardiovascular disease, autoimmune disease and cancer should be above 30 ng/mL for optimal health benefit

  • The expert panel agreed on an upper safety limit for 25(OH)D of 100 ng/mL

  • In these patients, a large correcting dose can be proposed initially, followed by a maintenance treatment of 800 IU/day (or equivalent with intermittent dosing), which can be increased if levels remain insufficient during

Acknowledgements

The authors are grateful to Ismar Healthcare for their assistance in editing of the manuscript. The Vitamin D Summit Meeting was financially supported by DiaSorin S.p.A.

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