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


CONCLUSIONS
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.
Carrasco
Ruy
R
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. rcarrasco@sfcaustin.com
Lovell
Daniel J
DJ
Giannini
Edward H
EH
Henderson
Carol J
CJ
Huang
Bin
B
Kramer
Sandy
S
Ranz
Julie
J
Heubi
James
J
Glass
David
D
D000284:Administration, Oral; D000293:Adolescent; D000596:Amino Acids / Q000097:blood / Q000652:urine; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy / Q000652:urine; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D002648:Child; D003404:Creatinine / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood / Q000652:urine; D010281:Parathyroid Hormone / Q000097:blood; D010349:Patient Compliance; D010758:Phosphorus / Q000097:blood / Q000652:urine; D010919:Placebos; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D014815:Vitamins / Q000008:administration & dosage / Q000097:blood / Q000652:urine
D000596:Amino Acids; D015415:Biomarkers; D010281:Parathyroid Hormone; D010919:Placebos; D014815:Vitamins; D015675:Osteocalcin; D014807:Vitamin D; D010758:Phosphorus; C015484:pyridinoline; D003404:Creatinine; D002118:Calcium