Randomised controlled trial of vitamin D supplementation in sarcoidosis

Abstract

Objectives: The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain. However, authoritative reviews have recommended avoiding sunlight exposure and vitamin D supplements, which might lead to adverse skeletal outcomes from vitamin D insufficiency. We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency.

Design: Randomised, placebo-controlled trial.

Setting: Clinical research centre.

Participants: 27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D (25OHD) <50 nmol/L.

Intervention: 50 000 IU weekly cholecalciferol for 4 weeks, then 50 000 IU monthly for 11 months or placebo.

Primary and secondary outcome measures: The primary endpoint was the change in serum calcium over 12 months, and secondary endpoints included measurements of calcitropic hormones, bone turnover markers and bone mineral density (BMD).

Results: The mean age of participants was 57 years and 70% were women. The mean (SD) screening 25OHD was 35 (12) and 38 (9) nmol/L in the treatment and control groups, respectively. Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks, 84 nmol/L at 6 months and 78 nmol/L at 12 months, while levels remained stable in the control group. 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks, but not at 6 or 12 months. There were no between-groups differences in albumin-adjusted serum calcium, 24 h urine calcium, markers of bone turnover, parathyroid hormone or BMD over the trial. One participant developed significant hypercalcaemia after 6 weeks (total cholecalciferol dose 250 000 IU).

Conclusions: In patients with sarcoidosis and 25OHD <50 nmol/L, vitamin D supplements did not alter average serum calcium or urine calcium, but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia.

Trial registration: This trial is registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au). The registration number is ACTRN12607000364471, date of registration 5/7/2007.

Keywords: THORACIC MEDICINE.

Figures

Figure 1

Flow of participants.

Figure 2

The effect of vitamin D supplementation on 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Data are mean and 95% CI. p Values are for time-by-treatment interaction. Asterisks indicate significant between-groups differences at individual points.

Figure 3

The effect of vitamin D supplementation on albumin-adjusted serum calcium and 24 h urine calcium levels. Data are mean and 95% CI. p Values are for time-by-treatment interaction.

Figure 4

The effect of vitamin D supplementation on bone turnover markers and serum parathyroid hormone. Data are mean and 95% CI. p Values are for time-by-treatment interaction. P1NP, Procollagen type-I N-terminal propeptide; β-CTx, β-C-terminal telopeptide of type I collagen.

Figure 5

The effect of vitamin D supplementation on bone mineral density (BMD). Data are mean and 95% CI for the percentage change from baseline adjusted for baseline BMD. p Values are for time-by-treatment interaction.