Strontium ranelate improves bone mineral density in thalassemia major related osteoporosis and reduces sclerostin levels

Patients with thalassemia major (TM) show reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment of postmenopausal and male osteoporosis. This randomized, placebo controlled study was designed to evaluate the effects of SrR on bone mineral density (BMD), bone turn-over markers and Wnt signaling modulators as sclerostin and DKK-1. Twenty-four TM osteoporotic women were randomized to receive daily SrR 2g or placebo in addition to calcium (1 gr) and vitamin D (800 IU). BMD at lumbar spine and femoral neck, bone turn-over markers (C-terminal telopeptide of procollagen type I [CTX]; bone specific alkaline phosphatase [BSAP]), IGF-1, and Wnt signaling inhibitors (sclerostin, DKK-1) were assessed at baseline and after 24 months. Back pain was measured by visual analogue scale (VAS) 6-monthly. After 24 months, TM women treated with SrR increased their spine BMD values in comparison to baseline (+4%, p<0.05), but no significant change was observed at femoral site. Only in SrR group, bone turn-over markers significantly changed, with a reduction of CTX (0.69±0.19 vs 0.60±0.15 ng/ml, at baseline and after 24-months, respectively, p<0.05) and an increase of BSAP levels (14.85±1.91 vs. 17.3±3.06; p<0.05); sclerostin, but not DKK-1 levels were also reduced by SrR treatment (-17%, p<0.05). A significant reduction of back pain was already observed at 18 months (-30% vs. baseline values) in the SrR group and was maintained at 24 months (-60% and -30% vs. baseline and placebo values, respectively) (p<0.05). Our study reports for the first time the effects of SrR in TM related osteoporosis; SrR treatment improved BMD and normalized bone turn-over markers, reduced also sclerostin serum levels and improved back pain.