Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

Abstract

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m² , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.

Keywords: Elderly; IOM; bone markers; bone mineral density (BMD); high-dose vitamin D.

Figure 1

CONSORT flow diagram detailing recruitment status from pre-screening to study completion.

Figure 2

25OHD, PTH, Cross Laps, osteocalcin, and 1,25(OH)₂D levels by vitamin D supplementation high dose (closed circles) and low dose (open circles) groups. Numbers expressed as mean ± SEM. P-values depicted in the Figure are derived from repeated measures ANOVA within each treatment group. Values within each treatment group depicted with different letters are significantly different from each other in post-hoc analyses by ANOVA. *p<0.05 by independent t-test for 25OHD and 1,25(OH)₂ D at 12 months.

Figure 3

Percent change in BMD at 12 months, at various skeletal sites, by vitamin D treatment dose. Numbers expressed as mean ± SEM. BMD increased significantly at 12 months both at spine and total hip in both treatment groups, and at the sub-total BMD in the high dose treatment arm only. * p<0.05 for the % change at 12 months low dose vs. high dose by independent t-test.