Research Article: Randomized controlled trial of vitamin D supplementation in older people to optimize bone health

Date Published: January 08, 2019

Publisher: Oxford University Press

Author(s): Terry J Aspray, Thomas Chadwick, Roger M Francis, Elaine McColl, Elaine Stamp, Ann Prentice, Alexander von Wilamowitz-Moellendorff, Inez Schoenmakers.

http://doi.org/10.1093/ajcn/nqy280

Abstract

Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results.

This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry.

A total of 379 adults aged ≥70 y (48% women; mean age: 75 y) from the northeast of England were randomly allocated to 1 of 3 doses of vitamin D3 [12,000 international units (IU), 24,000 IU, or 48,000 IU] given once a month. The primary outcome was change in BMD (ΔBMD) at the hip. Secondary endpoints comprised the dose effects on femoral neck BMD, falls, circulating calciotropic hormones, bone turnover markers, and adverse events.

The mean ± SD baseline plasma 25-hydroxyvitamin D [25(OH)D] concentration was 40.0 ± 20.1 nmol/L, which increased after 12 mo to a mean 25(OH)D of 55.9, 64.6, or 79.0 nmol/L for participants receiving a monthly dose of 12,000, 24,000, or 48,000 IU, respectively (P < 0.01 for difference). There was no between-group difference in ΔBMD. However, parathyroid hormone concentrations decreased in all 3 groups, with a significantly greater decrease in the 48,000-IU group compared with the 12,000-IU group (P < 0.01). There were no differences in any adverse events between groups, with 3 cases of hypercalcemia, none of nephrolithiasis, and 249 falls observed. There was no difference in change in BMD over 12 mo between the 3 doses of vitamin D, suggesting no effect of the intervention or a similar attenuation of the anticipated decrease in BMD over 12 mo. The treatment was safe and effective in increasing plasma 25(OH)D concentrations, with no dose-related adverse events. This trial was registered at the EU Clinical Trials Register (EudraCT 2011-004890-10) and the ISRCTN Registry (ISRCTN35648481).

Partial Text

Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, impairment of muscle function, and an increased risk of falls and fractures. The results of clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD), bone loss, falls, and fractures have yielded conflicting results, and, although a recent meta-analysis of clinical trials reported a possible relation between vitamin D supplementation and higher BMD at the neck of femur, it suggested that supplementation with vitamin D has a benefit for bone health only in those at risk of vitamin D deficiency (1).

The Vitamin D Supplementation in Older People (VDOP) Trial (ISRCTN35648481) was a single-center, parallel-group, participant-randomized, double-blind interventional trial testing the effects on hip BMD of 3 doses—300, 600, and 1200 µg (12,000, 24,000, and 48,000 IU)—of oral vitamin D3 given each month to men and women aged ≥70 y for 1 y as described earlier (12), with the first dose given between November 2012 and May 2013. The study was funded by Arthritis Research UK (D19544). Potential participants were identified from electronic medical records from 25 general practitioner practices in the northeast of England. Participants were invited to take part after ensuring they did not meet the following exclusion criteria:
treatment with anti­resorptive or anabolic treatment for osteoporosis in the previous 3 y;current consumption of supplementary vitamin D at a dose >10 μg (400 IU)/d or calcium at a dose >500 mg/d;experience of a fragility fracture in the previous 6 mo;a history of renal stones, previous bilateral hip replacements, or primary hyperparathyroidism;past or present history of hypercalcemia (albumin ­adjusted plasma calcium >2.60 mmol/L), hypocalcemia (albumin­ adjusted plasma calcium <2.15 mmol/L), or an estimated glomerular filtration rate <30 mL · min−1 · 1.73 m−2. A total of 379 participants were recruited, with 343 (91%) participants completing the study at 12 mo [see Figure 1; Consolidated Standards of Reporting Trials (CONSORT) diagram]. Baseline characteristics, including anthropometric parameters, markers of calcium and vitamin D metabolism and intakes, renal function, falls, and major osteoporotic or hip fracture risk, were well balanced across the 3 arms (see Table 1). There was also no difference in self-reported habitual sun exposure between the 3 arms at baseline. There were no differences between arms in subsequent dropout from the study. The mean ± SD baseline 25(OH)D concentration was 40.0 ± 20.1 nmol/L. There was no significant dose effect on BMD at the total femur or neck of femur when giving a monthly dose of 12,000, 24,000, or 48,000 IU vitamin D. This is equivalent to a daily dose of 10, 20, or 40 µg (400, 800, and 1600 IU), respectively. The primary objective of this study was to evaluate the dose effect of vitamin D supplementation on the attenuation of the age-associated decline in BMD (12, 19), and our results complement a recent meta-analysis by Reid et al. (1), which concluded that there was no clinically significant effect of vitamin D supplementation on BMD, although that study showed a 0.8% greater BMD at the neck of femur over a mean study duration of 2 y. A more recent study (not included in Reid et al.'s meta-analysis) showed a significant effect of vitamin D supplementation on total hip BMD, at a dose of 25 µg (1000 IU) but not at 10 µg (400 IU)/d, when compared with placebo (19). Of note, the latter study, performed in Aberdeen, United Kingdom, recruited a younger population than ours (mean age: 65 y), comprising only women who also had a lower mean serum 25(OH)D concentration at baseline (34 nmol/L) (19). However, it is difficult to compare the results of either the meta-analysis or the Aberdeen study with the VDOP because both evaluated the effect of vitamin D compared with placebo, whereas the VDOP was a dose-ranging study, with the 10-µg (400-IU)/d equivalent dose as reference.   Source: http://doi.org/10.1093/ajcn/nqy280

 

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