A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia

Abstract

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of beta-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than -1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3-15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5-12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5-12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7-6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in beta-thalassaemia-associated osteopenia.

Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration

“…encouraging results in this setting. 4,19,20 It increases BMD of L1-L4/R/FN even after its discontinuation. 5 ZOL mode of action includes mainly osteoclast inhibition.…”

Continuous Increase in Erythropoietic Activity despite the Improvement in Bone Mineral Density by Zoledronic Acid in Patients with Thalassemia Intermedia-Induced Osteoporosis

“…The placebo group showed an aggravation of BMD of all studied sites, although of nonsignificant difference, and a dramatic increase in CTX (p = 0.001) after 12 months of therapy. The results of this study suggest that zoledronic acid is an effective agent for the management of TI-induced osteopenia/osteoporosis, as in TM-induced bone loss [7, 8, 11, 12]. This is mainly due to the reduction in the increased bone resorption, which is present in thalassemia [4,5,6, 9] and assessed here by the measurement of CTX.…”

Talasemi Osteoporozunda Zoledronik Asit Kullanımı: İki Olgu Sunumu ve Literatürün Gözden Geçirilmesi

“…Olguların lomber KMY ölçümlerinde belirgin düzelme saptanmış ve tedaviye başlandıktan sonra yeni kırık oluşmamıştır. Birinci olguda tedavi aralıklarının daha sık olmasının sebebi sık kırık öyküsü olmasıdır ve bu konu ile ilgili yapılan yayınlarda da farklı aralıklarla uygulamalar yapılmıştır (2,(16)(17)(18)(19).…”