Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals

Background: A variety of studies demonstrated that vitamin D supplementation may reduce the risk of falls by 16% and higher 25(OH) D concentrations were associated with better lower-extremity function.

Objective: The objective of the study was to investigate long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men.

Methods: This study was 20-month, double-blinded, randomized, and controlled trial. The study included ambulatory women and men 70 years of age or older who were recruited through newspaper advertisements and mailing lists. The inclusion criterion was a 25-(OH) D serum level below 78 nmol/l. The exclusion criteria included hypercalcemia or primary hyperparathyroidism; fractures of the extremities due to osteoporosis; therapy with thiazide, bisphosphonate, calcitonin, vitamin D and vitamin D metabolites, estrogen, anti-estrogen in the past sixth months or fluoride treatment in the past two years. Furthermore, known intolerance to study medication, chronic renal failure, history of drug or alcohol abuse, nicotine abuse, more than seven cups of coffee daily, schedule holidays along the geographic longitude during the study period, diabetes mellitus and severe cardiovascular disease were also excluded. 121 participants were assigned to each treatment group. The study participants took either one tablet containing 500 mg of elemental calcium in the form of calcium carbonate or one tablet with 500 mg of elemental calcium and 400 IU of cholecalciferol at breakfast and dinner together with the meals. Both groups received the treatment over a period of 12 months which was followed by 8 months without treatment until month 20. The main outcome measure was the occurrence of falls at months 20 as determined by diaries. Secondary endpoints include non-vertebral fractures, isometric leg extensor strength, body sway total path length, timed-up-and-go or TUG test score, serum 25(OH) D, and parathyroid hormone levels.

Results: Baseline characteristics including age, height, weight, gender, serum 25 (OH) D, nutritional calcium intake, and intact parathyroid hormones level were not different in both treatment groups. Compared to baseline, an expected increase in mean serum 25(OH) D level was observed after 12 months of treatment in the calcium plus vitamin D group, whereas 25 (OH) D levels were similar to baseline in the calcium mono group (p<0.001 compared to baseline versus p<0.001 compared to calcium mono). By the end of treatment-free observation period 25 (OH) D levels had decreased to below baseline levels in both groups and were still significantly higher in the calcium plus vitamin D group.
Parathyroid hormone levels in both groups showed a similar decline by month 12 and were no longer different to baseline values by the end of the observation period.
 Quadriceps strength at the left leg was significantly higher in the calcium plus vitamin D group at month 12 when compared to either baseline (p<0.001) or the calcium mono group (p<0.01). This difference remained statistically significant at the end of the observation period.
 Similar results were observed with respect to the timed-up-and-go test: significant decreases in the mean time needed to perform the test were observed during treatment with calcium plus vitamin D compared to baseline (p<0.001) as well as to the calcium mono group (p<0.05). These differences remained significant at the end of the trial (p<0.001 compared to baseline versus p<0.05 compared to calcium mono).
No differences in body sway were seen at month 12 in comparison to baseline. At the end of the observation period; however, the former calcium plus vitamin D group showed a significant improvement in body sway compared to baseline (p< 0.001) as well as to the calcium mono group (p<0.05).
Falls were followed by diaries and decreased significantly over time. The cumulative development of the number of subjects with no falls is shown in a Kaplan Meier analysis. During this 20 months lasting clinical trial, 63% of the individuals in the calcium mono group versus 40% in the calcium plus vitamin D group had at least one fall (p<0.001). The mean number of falls per group was 1.41 in the calcium plus vitamin D group and 0.63 in the calcium plus vitamin D group (p<0.001). This translated into a total number of falls of 171 in the calcium mono group and 76 falls in the calcium plus vitamin D group. The time to first fall was evaluated using Cox regression analysis providing a 95% confidence interval. Concerning the time to the first fall, a 27% reduction in the vitamin D plus calcium group as compared to the calcium mono group was observed. This reduction was statistically significant (RR=0.73; 95% CI 0.54-0.96; p<0.01). At month 20 this comparable reduction reached 39% and was also statistically significant (RR=0.61; 95% CI 0.34-0.76; p<0.01). This reduced number of falls was accompanied by a reduction in the number of fractures: 19 fractures in the calcium mono group and 12 fractures in the calcium plus vitamin D group (p=0.12). In total, 13 subjects in the calcium mono group and 7 participants in the calcium plus vitamin D group experienced at least one fracture (p=0.08). The authors concluded that combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.

Strengths: P value was reported for each outcome measure.

Weaknesses: The power of the study was not reported for secondary outcome measurement, number of fractures which makes type II error possible. Side effects of drugs were not assessed and mentioned in the study. In addition, other confounding factors such as concomitant use of medications that can induce falls; diet; sun exposure; and physical activity could have affected the study results as well. Meda Pharma Inc. which markets vitamin D and calcium funded this study which may cause a potential of conflict.

Conclusion: Calcium plus vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improve muscle function in the elderly. However, it should be noted that the assessment of falls based on diaries and phone interviews solely is not sufficient and reliable. Future studies could have weekly visits in addition to daily diaries and phone interviews just in case falls may have been forgotten by the patients. Another consideration is concomitant use of medications was not reported in this study; therefore, the risk of medication-induced falls is another concern.  

Prepared by: Khan-ha Nguyen, Doctor of Pharmacy Candidate