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Bisphosphonates improve BMD in pediatric rheumatic disease



Prophylactic treatment with bisphosphonates could significantly improve bone mineral density (BMD) in children and adolescents receiving steroids for chronic rheumatic disease, a study has found.

A paper published in EClinicalMedicine reported the outcomes of a multicenter, double-dummy, double-blind, placebo-controlled trial involving 217 patients who were receiving steroid therapy for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, or juvenile vasculitis. The patients were randomized to risedronate, alfacalcidol, or placebo, and all of the participants received 500 mg calcium and 400 IU vitamin D daily.

Lumbar spine and total body (less head) BMD increased in all groups, but the greatest increase was seen in patients treated with risedronate.

After 1 year, lumbar spine and total body (less head) BMD had increased in all groups, compared with baseline, but the greatest increase was seen in patients who had been treated with risedronate.

The lumbar spine areal BMD z score remained the same in the placebo group (−1.15 to −1.13), decreased from −0.96 to −1.00 in the alfacalcidol group, and increased from −0.99 to −0.75 in the risedronate group.

The change in z scores was significantly different between placebo and risedronate groups, and between risedronate and alfacalcidol groups, but not between placebo and alfacalcidol.

“The acquisition of adequate peak bone mass is not only important for the young person in reducing fracture risk but also has significant implications for the development of osteoporosis in later life, if peak bone mass is suboptimal,” wrote Madeleine Rooney, MBBCH, from the Queens University of Belfast, Northern Ireland, and associates.

There were no significant differences between the three groups in fracture rates. However, researchers were also able to compare Genant scores for vertebral fractures in 187 patients with pre- and posttreatment lateral spinal x-rays. That showed that the 54 patients in the placebo arm and 52 patients in the alfacalcidol arm had no change in their baseline Genant score of 0 (normal). However, although all 53 patients in the risedronate group had a Genant score of 0 at baseline, at 1-year follow-up, 2 patients had a Genant score of 1 (mild fracture), and 1 patient had a score of 3 (severe fracture).

In biochemical parameters, researchers saw a drop in parathyroid hormone in the placebo and alfacalcidol groups, but a rise in the risedronate group. However, the authors were not able to see any changes in bone markers that might have indicated which patients responded better to treatment.

Around 90% of participants in each group were also being treated with disease-modifying antirheumatic drugs. The rates of biologic use were 10.5% in the placebo group, 23.9% in the alfacalcidol group, and 10.1% in the risedronate group.

The researchers also noted a 7% higher rate of serious adverse events in the risedronate group, but emphasized that there were no differences in events related to the treatment.

In an accompanying editorial, Ian R. Reid, MBBCH, of the department of medicine, University of Auckland (New Zealand) noted that the study was an important step toward finding interventions for the prevention of steroid-induced bone loss in children. “The present study indicates that risedronate, and probably other potent bisphosphonates, can provide bone preservation in children and young people receiving therapeutic doses of glucocorticoid drugs, whereas alfacalcidol is without benefit. The targeted use of bisphosphonates in children and young people judged to be at significant fracture risk is appropriate. However, whether preventing loss of bone density will reduce fracture incidence remains to be established.”

The study was funded by Arthritis Research UK. No conflicts of interest were declared.

SOURCE: Rooney M et al. EClinicalMedicine. 2019 Jul 3. doi: 10.1016/j.eclinm.2019.06.004.

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