“Vitamin D – why does it matter?” – Defining Vitamin D deficiency and its prevalence

Abstract

Vitamin D deficiency is prevalent in about 50 % of adults and limited data support a similar prevalence in children. This is of concern, as vitamin D deficiency is a risk factor for falls and fractures and several double-blind RCTs provide evidence that supplementation reduces the risk of fall and fractures among the senior population. Further, large epidemiologic studies consistently report that vitamin D deficiency confers an increased risk of mortality, cardiovascular disease and cancer, especially colo-rectal cancer. However, as large clinical trials for non-musculoskeletal endpoints are missing today, public health recommendations are based primarily on bone health to argue vitamin D repletion in the population.

Key Words::

• vitamin D deficiency
• falls
• fractures
• children
• adults

Introduction

Most reports on the prevalence of vitamin D deficiency support that about 50 % of adults and children are vitamin D deficient, reaching 25-hydroxyvitamin D (25(OH)D) serum concentrations below 50 nmol/L [1]. Further, several studies support that 60 to 70 % of the adult population, including those treated for osteoporosis [2], and over 90 % of hip fracture patients [3,4], may not reach a desirable serum concentration of 75 nmol/L for optimal bone mineral density [5], fall and fracture reduction [6]. This is of concern, as we have evidence today that vitamin D supplementation of about 800 IU per day may reduce non-vertebral fractures, including those at the hip, and falls in the senior population by about 20 % [7–10]. Vitamin D has a unique potential for fracture prevention at older age because of its dual benefit on fall and fracture prevention [11,12]. As 75 % of all fractures occur in those aged 65 and older [13], falls are the primary risk factor for fracture [14,15], and the senior population in Europe, the US and large parts of the world will double by 2030 [16], such benefits have major public health implications.

Vitamin D supplementation for bone health and fracture prevention is supported by the Institute of Medicine (IOM) [17], the International Osteoporosis Foundation (IOF) [18], and the Endocrine Society [19]. Further, given the available evidence today, vitamin D supplementation for fall prevention is supported by the Agency for Healthcare Research and Quality (AHRQ) for the U.S. Preventive Services Task Force [20], the 2010 American Geriatric Society/British Geriatric Society Clinical Practice Guideline [21], the 2010 assessment by the IOF [18], and the US Endocrine Task Force on Vitamin D [19], all four of which identified vitamin D as an effective intervention to prevent falling in older adults based on their review of the evidence. In contrast to all published and peer reviewed meta-analysis, the meta-analysis commissioned by the IOM (never peer reviewed individually), has a misleading conclusion that the evidence of vitamin D regarding fall prevention is inconsistent and therefore insufficient. The IOM overall analysis of 12 randomized trials (n = 14,101) showed a significant benefit of vitamin D on fall prevention (OR = 0.89; 95 % CI 0.80–0.99), as did the majority of their subset analyses, clearly supporting the use of vitamin D in the prevention of falling [7].

Beyond the evidence on fall and fracture prevention, large observational studies, mechanistic data and small clinical trials suggest benefits of vitamin D relevant to general health. These data are discussed by other authors in this review and need confirmation from a large clinical trial. Notably, however, the majority of epidemiologic data that link 25(OH)D status to cardio-vascular health [22–25], cancer incidence (especially incidence of colo-rectal cancer [26,27]), and mortality [22,28–31] suggest that serum concentrations between 75 and 110 nmol/L confer the lowest risk of disease [6]. Limited data suggest that very low and high serum concentrations of 25(OH)D may increase the risk of mortality [30,32].

As a next step to define the role of vitamin D supplementation for general health endpoints (cardiovascular health, cognitive decline, functional decline, immunity) two large RCTs have been funded: VITAL has been funded by the NIH and is currently recruiting (principal investigator JoAnn E. Manson); DO-HEALTH has been funded by the European Commission and is planned to start recruitment in 5 European countries in June/July 2012 (prinicipal investigator Heike A. Bischoff-Ferrari).

Defining vitamin D deficiency

25(OH)D serum concentrations of less than 50 nmol/L (< 20 ng/mL) are considered as indicative of vitamin D deficiency. Severe vitamin D deficiency is marked by a threshold of less than 25 nmol/L (< 10 ng/mL) and vitamin D insufficiency by concentrations in the range of 25 to 49 nmol/L (10–19 ng/mL) [19]. At a concentrations below 25 nmol/L (< 10 ng/mL) adverse effects like rickets and osteomalacia are observed in children and adults, and increased bone resorption and elevated risk for secondary hyperparathyroidism are seen at concentrations between 25 and 49 nmol/L (10–19 ng/mL).

The Institute of Medicine recommends a 25(OH)D threshold of at least 50 nmol/L as an adequate 25(OH)D concentration to support bone health in all age groups.

A 25(OH)D threshold of 75 nmol/L (30 ng/mL) is needed for optimal bone mineral density in younger (age 19–49 yrs) and middle aged adults (age 50+) in the largest population-based study (NHANES III [5]), and fracture and fall prevention in adults age 60 yrs and older based on double-blind randomized controlled trials [6,8, 9,33], consistent with the IOF [18] and the US Endocrine Society [19].

Regarding general health endpoints, the Institute of Medicine in agreement with the US Endocrine Society, suggests that evidence from RTCs is lacking. The Endocrine Society, however, states that numerous epidemiological studies have suggested that 25(OH)D serum concentrations of 75 to 110 nmol/L (30 to 44 ng/mL) may have additional health benefits in reducing the risk of common cancers, autoimmune diseases, type 2 diabetes, cardiovascular disease, and infectious diseases [22,23,25,34,35].

Prevalence of vitamin D deficiency

Children

In a larger survey of German children (KIGGS) age 1 to 17 yrs, median 25(OH)D concentrations were 44 nmol/L among native children, and 35 nmol/L among immigrant children [36]. Concentrations in boys and girls were similar, however, there was a some decline with age with the highest median concentrations measured in the first year of life, likely due to the German supplementation recommendation of 500 IU per day (12.5 μg/d) in infants of this age group [36]. The Optiford study of 4 Northern European countries (Denmark, Finland, Poland, Ireland) included 199 children with a mean age of 12.5 years who had in 30 % to 50 % of the cases serum 25(OH)D concentrations below 25 nmol/L, and in over 90 % of the cases serum concentrations were below 48 nmol/L [37]. The same study also assessed 25(OH)D concentrations in senior adults and suggested that in comparison, vitamin D deficiency was more prevalent in children [37].

Adults

In a large survey in 1992 of 3,276 Swiss adults aged 25 to 75 years, 25(OH)D concentrations were relatively stable across age groups. The median concentration was 46 nmol/L, 34 % had concentrations below 38 nmol/L, and about 70 % had concentrations below 75 nmol/L [38]. These data are largely consistent with other European countries [39], the US [40] and many regions of the world [1].

Older adults and hip fracture patients

Most vulnerable to vitamin D deficiency are older adults with acute hip fracture who were found to have severe vitamin D deficiency (< 30 nmol/L) in 50 % of cases, both in Europe and in the US [3,4]. In general, older adults are at an increased risk for vitamin D deficiency for avoiding direct sun exposure, for being unable to get sufficient sun exposure due immobility, and due to reduced skin production of vitamin D with age [41]. In the European SENECA study, 36 % of older men and 47 % older women had 25(OH)D serum concentrations below 30 nmol/L [42]. Also in the US, NHANES III [5,40] and IV [43] confirm a high prevalence of vitamin D deficiency in the oldest segment of the US population. Notably, in an international survey of postmeopausal women treated for osteoporosis, 64 % did not reach a serum concentration of 75 nmol/L [2], the desirable threshold supported by the evidence from double-blind randomized controlled trials for optimal non-vertebral fracture prevention [8].

Declaration of interest: The author report no conflicts of interest. The author alone is responsible for the content and writing of the paper.