Daily supplementation with calcium and vitamin D boosted bone mineral density by a small but statistically significant amount in children with juvenile rheumatoid arthritis who were not being treated with corticosteroids, according to findings from a randomized, double-blind, placebo-controlled trial.
“Since peak bone mass is achieved no later than the end of the second decade of life, efforts to increase bone mineralization in children with JRA must be started at an early age,” said Dr. Daniel J. Lovell of the Cincinnati Children's Hospital Medical Center and his associates.
The investigators were cautious in their interpretation of the findings, however, concluding that the increase in bone mineral density (BMD) was not enough to provide “strong support” for the use of routine calcium supplementation in children with JRA who are not taking corticosteroids. The 198 children in the study had not received corticosteroids for at least 3 months prior to the 24-month study, and many had normal or nearly normal baseline BMD.
The children, aged 6-18 years (mean age of 12 years), had had JRA for a mean of 6 years. They were randomized to receive two daily oral tablets—either an oral supplement of 1,000 mg calcium (taken as 2,500 mg calcium carbonate) and a tablet containing 400 IU of vitamin D, or a matched placebo tablet and 400 IU of vitamin D, for 24 months.
They underwent dual x-ray absorptiometry at baseline and then every 6 months, and their adherence to the treatment regimen was regularly assessed. They were permitted to continue taking nonsteroidal anti-inflammatory drugs and antirheumatic medications. Patients in both treatment groups had similar levels of physical activity and dietary intake of calcium at baseline and throughout the study.
At baseline, the mean total body BMD was 0.89 gm/cm2 among patients randomized to receive calcium, and 0.87 gm/cm2 among those randomized to receive placebo. At 24 months, the total body BMD had increased to 0.95 gm/cm2 in the calcium group (a 6.7% increase) and 0.92 gm/cm2 (a 5.8% increase) in the placebo group.
Similarly, patients treated with calcium had a higher lumbar spine BMD—and a higher percentage change in lumbar spine BMD—than did control patients. But, “as expected, all patients demonstrated increases in (total body BMD) and lumbar spine BMD,” Dr. Lovell and his associates said (Arthritis Rheum. 2006;54:2235-42).
When the investigators adjusted for baseline differences in BMD and relevant “outcome effect modifiers,” they found significantly higher total body and mean lumbar spine BMD in patients who received calcium.
The increased rate of bone mineralization in the calcium group was seen during the first 18 months only, however. For the last 6 months of the study, BMD increased at a similar rate in both groups, “suggesting that a threshold for the biologic effect of Ca supplementation had been reached,” the investigators said.
And although statistically significant, the increases in BMD were surprisingly small, they said. Based on an earlier small, open study that showed increased bone mineralization with calcium supplementation, the investigators had projected a 10% greater increase in total body BMD in calcium-treated patients.
The “modest response … may be a reflection of the pathogenic mechanisms of JRA-associated osteopenia,” they wrote. “The potency of [inflammatory cytokines] to mediate BMD, and their systemic overproduction in autoimmune diseases such as JRA may be difficult to overcome with oral calcium treatment alone.”
Adherence to the supplementation regimen was “very good overall” in the study—much higher than in other studies—which means that “the effect of calcium supplementation, when used as part of routine clinical care … may therefore be less than the effect seen [here],” they said.
The study did not address the role of calcium supplementation in patients with JRA who require treatment with corticosteroids or who already have significantly decreased BMD, they noted.