Clinical Question: In older persons who have already experienced an osteoporosis-related fracture, does vitamin D, calcium, or the combination prevent secondary fractures?
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Two studies conducted in the United Kingdom examined the effect of calcium and vitamin D on the prevention of secondary fractures. In the first study, researchers recruited 5,292 patients following treatment for a fracture. Most (85 percent) were white women and all were at least 70 years of age, ambulatory, and had a previous osteoporotic fracture an average of one month before entering the study. Approximately 20 percent of participants were taking a thiazide diuretic, which blocks calcium excretion. Using concealed allocation to avoid selective enrollment of patients, the researchers randomly assigned patients to receive 800 IU per day of oral vitamin D3, 1,000 mg of calcium, a combination of both, or placebo. The patients were assigned treatment for at least two years.
Overall, new fractures occurred in 13.0 percent of the participants; hip fracture, the more clinically relevant outcome, occurred in 3.4 percent of participants. Compliance was poor in the study: by two years, only one half of the patients were still taking their assigned treatment. The two groups taking calcium had significantly higher rates of noncompliance, with only 42 percent still taking their assigned treatment at two years. The results were analyzed using intention to treat, which leaves patients in their assigned groups even if they dropped out of the study or were not compliant. Supplementation with calcium, vitamin D, or the combination was ineffective in decreasing the rate of any fracture or hip fracture. Compliant patients also did not have lower rates of fractures, although the number of patients (508) taking vitamin D and calcium may not have been large enough to find a difference, if one existed.
In the second study, researchers surveyed general practices across England to find women 70 years or older who had a previous fracture or at least one of the following risk factors: low body weight, maternal history of fracture, smoking, or poor to fair health. The 3,314 women were randomized, using concealed allocation, to receive placebo or a combination of 1,000 mg of calcium and 800 IU of vitamin D3. Over a median follow-up of slightly more than two years, 4.3 percent of women experienced a fracture and 0.7 percent experienced a hip fracture. Similar to the first study, there was no difference in the rates of any fracture or hip fracture with treatment among all patients or in those who were compliant.
Bottom Line: The combination of 1,000 mg of calcium and 800 IU of vitamin D3 was ineffective in preventing fractures in two studies that involved more than 8,500 participants, almost all of whom were women, at least 70 years of age, with a previous osteoporotic fracture or high risk for a fracture. The dosage of calcium is lower than the 1,500 mg per day commonly recommended. These results conflict with a meta-analysis showing that combination therapy reduced the rate of fractures, including hip fracture, in older patients who had not had a previous hip or nonvertebral fracture (Bischoff-Ferrari HA, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA May 11, 2005;293:2257–64). (Level of Evidence: 1b)