Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis

Briana Gray, PharmD, St. Cloud VA Health Care System

Background: Fractures in community-dwelling older adults often involve a complicated recovery and loss of independence. Unfortunately, more than 20% of older adults die within the first year after a hip fracture. Current clinical guidelines recommend calcium and vitamin D supplementation to prevent osteoporosis and fractures, though previous data has yet to show a consistent benefit of supplementation.

Objective: To determine if calcium, vitamin D, or combined supplementation are associated with reduced fractures in community-dwelling older adults.

Study Design: A systematic review and meta-analysis of previously published systematic reviews and meta-analyses was obtained by searching the PubMed, Cochrane library, and EMBASE databases for calcium, vitamin D, and fracture. Publications from December 24, 2006 to December 24, 2016 studying the incidence of fracture in community-dwelling adults were included in the analysis. A similar second search was performed to identify individual studies published from July 16, 2012 to July 16, 2017.

Randomized controlled trials (RCTs) were included if they compared calcium, vitamin D, or both supplements to a placebo or no treatment group, included adults at least 50 years of age living in the community, and provided fracture data. Trials were excluded if they had no placebo or no treatment group, included corticosteroid-induced osteoporosis, included other osteoporotic treatments, used vitamin D analogs or hydroxylated vitamin D, or evaluated dietary intake. Each trial was then designated as low, moderate, or high quality based on blinding, randomization, and bias rating. Trials were assessed for bias by two researchers using the Cochrane risk-of-bias criteria.

Hip fracture was selected as the primary outcome because it is considered the most serious type of osteoporotic fracture. Secondary outcomes included rates of nonvertebral, vertebral, and total fractures. Risk ratios (RR), absolute risk differences (ARD), and 95% CIs were calculated using the Mantel-Haenszel method. Pooled data was evaluated using the random-effects model and the I2 statistic was used to evaluate heterogeneity between summary data. A sensitivity analysis was also performed that excluded low-quality trials, trials recruiting participants with particular conditions, or trials deemed different from the others. Subgroup analyses were conducted based on medication dosing and schedule differences, sex, fracture history, dietary calcium intake, and baseline vitamin D concentration. If 10 or more trials reported the primary outcome, a funnel plot was used to assess publication bias. All tests were two-tailed and p <0.05 was considered significant.

Results: Overall, 33 RCTs involving 51,145 patients were included after excluding duplicate trials. All studies were randomized and approximately 75% were also double-blind, placebo-controlled trials. Most trials were moderate quality, although one was low quality, and six were high quality. A publication bias analysis was not performed because fewer than 10 trials reported hip fracture in each comparison.

Calcium supplementation, vitamin D supplementation, and combination calcium and vitamin D supplementation were not significantly associated with hip, nonvertebral, vertebral, or total fractures compared to placebo or no treatment. There was no change in results in the sensitivity and subgroup analyses, except for patients with a baseline serum 25-hydroxyvitamin D level of ≥20 ng/mL, where vitamin D supplementation was associated with a significantly higher incidence of hip fracture (RR 1.49 [95% CI 1.03 - 2.17]; ARD 0.00 [95% CI 0.00 - 0.01]). When compared to patients with serum 25-hydroxyvitamin D level of <20 ng/mL, this result was not statistically significant. Once yearly high-dose vitamin D therapy was also associated with a higher incidence of hip fracture (RR 1.41 [95% CI 1.02 - 1.96]; ARD 0.00 [95% CI 0.00 - 0.01]).

Conclusions: Based on this meta-analysis of RCTs, supplementation with calcium, vitamin D, or combination supplementation compared to placebo or no treatment was not associated with a reduced fracture risk in community-dwelling older adults. The dose of supplementation, patient sex, fracture history, calcium intake, and baseline serum 25-hydroxyvitamin D level did not impact these findings.

Limitations: Not all studies included in the analysis tested baseline vitamin D level and vitamin D deficiency. This may be an area for further research. Due to the process for identifying RCTs, some acceptable trials may have been missed in the meta-analysis and systematic review search. Although the researchers used a relatively objective process for classifying the quality of the trials, some of the criteria could be subjectively interpreted and thus classified differently. Lastly, a few of the included trials used less desirable methods, such as uncertain allocation concealment, and were of poor quality.

Key Point: Supplementing with calcium, vitamin D, or both is not associated with reduced risk of fractures in community dwelling older adults compared to placebo or no treatment.

Reference:

  1. Zhao J, Zeng X, Wang J, Liu L. Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: a systematic review and meta-analysis. JAMA. 2017;318(24), 2466-2482.