Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial

Abstract

Objective: To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption.

Methods: In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover.

Results: One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies.

Conclusion: Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.

Trial registration: ClinicalTrials.gov NCT00000429.

Figures

Figure 1

Total Body BMD Profile Changes in Total Body bone mineral density (BMD) mean plot for ITT data (167 subjects) over 24 month period. BMD taken at baseline, 6, 12, 18 and 24 months. Increased total BMD noted in all patients (--▲--), but more notable in calcium (--♦--) group compared to placebo () group.

Figure 2

Serum Markers of Bone Turnover Mean plot for ITT data (167 subjects)

Figure 3

Changes in urine markers of bone turnover over time. Mean plot for ITT data (167 subjects) *Urine Ca/Cr Geometric mean was used

Figure 4

Lost to Follow-up Number of patients lost to follow-up at 6 month visits (0, 6, 12, 18 and 24 months). By 24 months 28% of patients had dropped out. The rate of drop-out between the between the CALCIUM and groups was not significantly different. No evidence to support informative dropout was noted between the groups.