Vitamin D Supplementation and Fracture Incidence in Elderly Persons

Vitamin D deficiency is common in elderly persons, especially those with hip fracture [1, 2]. It is caused by low exposure to sunshine, decreased synthesis of vitamin D3 in the aging skin, and a diet low in vitamin D [3, 4]. The mean vitamin D intake... show more

Vitamin D deficiency is common in elderly persons, especially those with hip fracture [1, 2]. It is caused by low exposure to sunshine, decreased synthesis of vitamin D3 in the aging skin, and a diet low in vitamin D [3, 4]. The mean vitamin D intake in elderly persons in the Netherlands is about 100 IU/d, half that of elderly persons in the United States [5]. Most of this vitamin D comes from margarine, which is the only vitamin D-supplemented food in the Netherlands (3 IU/g). In vitamin D deficiency, the low serum concentration of 25-hydroxyvitamin D [25(OH)D] leads to a low 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration and then to a higher serum parathyroid hormone concentration, especially in the winter [6-10]. Histologically, the increased parathyroid activity is associated with high bone turnover, leading to cortical bone loss and low density bone [5, 11], which may lead to hip fracture. We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [10]. Vitamin D3, 400 IU/d, led to an adequate increase of the serum 25(OH)D concentration, to a small but significant increase of the serum 1,25(OH)2D concentration, and to a decrease of the serum concentration of intact parathyroid hormone. It was recently observed [12, 13] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women. Therefore, it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation, it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [14]. These results suggest that vitamin D supplementation may reduce the incidence of hip fractures, because bone strength shows a strong correlation with bone mineral density [15]. However, increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength, as has been shown with sodium fluoride [16]. Bone structure and bone quality are also determinants of bone strength [17], and falls are a risk factor for hip fractures [18]. Therefore, hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation. Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients, because the outcome has an annual incidence of 0.5% to 4% in the elderly population [19]. We report the results of a large-scale, prospective study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures. Methods Participants The study included 2578 persons (1916 women and 662 men) 70 years of age and older (mean age SD, 80 6 years; range, 70 to 97 years). Participants were recruited from general practitioners, from apartment houses for elderly persons, and from homes for elderly persons in Amsterdam and its vicinity. Persons recruited from practitioners were living independently; those recruited from apartment houses and homes were receiving some care, but less than they would have received in a nursing home. Participants had to be reasonably healthy and able to give informed consent. Persons with a history of hip fracture or total hip arthroplasty, known hypercalcemia, sarcoidosis, or recent urolithiasis (< 5 years earlier) were excluded. Patients who had diseases or who used medications that influence bone metabolism (such as thyroid disease or glucocorticoid medication) were not excluded. The spontaneous use of vitamin D supplements and multivitamins was discouraged, but the prescription practices of the general practitioners were not altered. All vitamin use was carefully documented. The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital, and all participants gave informed consent. Study Design After checking the inclusion and exclusion criteria and obtaining informed consent, the participants were randomly assigned to receive either active treatment with vitamin D3 or placebo. The study was double-blind, and randomization was done in blocks of 10 per general practice, apartment house, or home. Randomization lists were made using a computerized random-number generator. Lists in sealed envelopes were sent to the hospital pharmacy for assignment. Each participant took either one tablet per day that contained vitamin D3, 400 IU, or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet. After enrollment, the participants received the first container of tablets (210 tablets). The container was replaced every 6 months with a full container. All participants were also advised in writing to consume at least three servings of dairy products per day (for example, 1 glass of milk, 1 cup of yogurt, and 1 slice of cheese) to ensure a calcium intake of at least 800 to 1000 mg/d. The study was started in August 1988. The last participant was enrolled in December 1990, and all participants had stopped using study medication by December 1993. The follow-up period had been planned to last no more than 3 years, but because the number of hip fractures during the study was lower than expected, a 6-month extension was planned. The study participants thus received medication for 3 to 3.5 years; those who received it for 3.5 years were those who consented to the 6-month extension. Total follow-up was to a maximum of 4 years. Data collected at baseline included an outdoor activity score (1 equals going outdoors less than once a week; 2 equals going outdoors 1 or 2 times per week; and 3 equals going outdoors 3 times per week or more) and a score for sunshine exposure (when outside: 1 equals in the shade as much as possible; 2 equals sometimes in sunshine; 3 equals much exposure to sunshine). These scores show a positive relation with serum 25(OH)D concentration [3]. Mobility was estimated by a walki show less