Vitamin D deficiency as a risk factor for osteoporotic fractures
Introduction
Vitamin D deficiency is very common in the elderly. The prevalence varies strongly between different studies, depending on the population and definition used [1]. Vitamin D deficiency in older persons is caused by insufficient sunlight exposure, a decreased functional capacity of the skin to synthesize vitamin D3 and low dietary vitamin D intake [1]. Vitamin D plays an important role in calcium homeostasis [1]. In addition, it stimulates bone growth while protecting osteoblasts from apoptosis [2].
Fractures are one of the most severe consequences of osteoporosis. Osteoporotic fractures are associated with impaired functioning, decreased quality of life, increased nursing home admission, increased mortality, and high health care costs [3], [4], [5], [6], [7], [8], [9]. In epidemiological studies, vitamin D deficiency has been associated with several determinants of fractures, such as low bone mineral density, muscle weakness, increased body sway and falls [10], [11], [12], [13]. Two meta-analyses show that the incidence of falls and fractures can be decreased by vitamin D supplementation [14], [15]. The meta-analysis on fractures suggests that the anti-fracture effect only exists for a vitamin D dose of 700 to 800 IU daily. Since the publication of this meta-analysis, five large trials were published that did not find an effect of vitamin D supplementation on fractures [16], [17], [18], [19], [20]. One of these studies used a vitamin D dose of 400 IU daily [18]; two studies used 800 IU daily [16], [17], one study used 100,000 IU four-monthly (equivalent to 822 IU daily) [20], and one study used 2.5 mg three-monthly (equivalent to 1100 IU daily) [19]. Two of these studies used ergocalciferol [19], [20].
Prospective cohort studies are needed to examine the strength of the association between different levels of serum 25(OH)D deficiency and fractures. Up till now, the association between low serum 25(OH)D levels and fracture risk was only examined in three large cohort studies [21], [22], [23]. The first study did find an association between serum 1,25-dihydroxyvitamin D and risk for hip fracture, but not for serum 25(OH)D. In addition, no association with vertebral fractures was found [21]. The second study found an increased fracture risk for a subgroup of women with 25(OH)D levels below 20 ng/ml, but not for 30 ng/ml [22]. The third study found an increased fracture risk for women with 25(OH)D levels below 12 ng/ml and 20 ng/ml, but these were explained by age [23]. In the latter study, no significant associations with fracture risk were found for women having 25(OH)D levels below 30 ng/ml.
Because the evidence on the association between vitamin D deficiency and fracture incidence is contradictory, the aim of the present study was to examine whether low serum 25(OH)D levels are associated with osteoporotic fractures. The study was performed using data of the LASA study, an ongoing multidisciplinary cohort study in a representative sample of older Dutch men and women. The analyses were performed using both commonly used cut points of serum 25(OH)D (< 10 ng/ml, 10–19.9 ng/ml, 20–29.9 ng/ml, ≥ 30 ng/ml), as well as the optimal cut point found in our dataset.
Section snippets
Subjects
LASA is an ongoing multidisciplinary cohort study on predictors and consequences of changes in physical, cognitive, emotional and social functioning in older persons [24]. A random sample of men and women aged 55 years and over, stratified by age, sex, urbanization grade and expected 5-year mortality rate was drawn from the population registers of eleven municipalities, in three regions of the Netherlands. In total, 3107 persons were enrolled in the baseline examination in 1992/93. For the
Results
In Table 1, the baseline characteristics are presented. In total, 115 persons had an osteoporotic fracture of which 31 (27.0%) were wrist fractures, 29 (25.2%) hip fractures, 14 (12.2%) rib fractures, 11 (9.6%) vertebral fractures and 30 (26.0%) other fractures. Persons with fractures were significantly older, were more often female, had a lower number of years of education, were more often cognitively impaired, and had a lower physical performance than persons without fractures. In addition,
Discussion
In this study, a statistically significant and independent relationship between serum 25(OH)D levels lower than or equal to 12 ng/ml and fractures was found in persons aged 65–75 years, while no association was observed for older persons. When using the commonly used cut points of serum 25(OH)D, significant associations in univariate analyses were observed, but these disappeared after adjustment for confounding.
One of the most striking results is that serum 25(OH)D was only associated with
Conflict of interest
Dr. Lips served as a consultant for Merck and received research grants from Merck. All other authors have no conflicts of interest.
Acknowledgments
This study is based on data collected in the context of the Longitudinal Aging Study Amsterdam (LASA), which is largely funded by the Ministry of Health, Welfare, and Sports of the Netherlands.
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