The effects of strontium ranelate on biochemical markers of bone turnover and their relationship with bone mineral density

Abstract

Dear Editors, We would like to comment on the article by Bruyere et al. [1]. In our opinion, the conclusion that short-term changes in biochemical markers of bone formation and their association with BMD changes suggest a bone-forming activity of strontium ranelate (SrR) is flawed, given the several limitations in this post hoc analysis that need to be considered. Biochemical markers of bone remodelling were assessed at baseline, after 3 and 6 months, and every 6 months thereafter over 3 years. However, only 3-month results are presented [1]. Given the lack of data at later time points, it can be argued that a single early measurement could be a spurious finding, and a full description of the changes of these biochemical markers over time would be more conclusive of the effects of SrR on bone remodelling. The authors state that early changes in markers are close to the coefficient of variation of the immunoassays, and in a substantial proportion of subjects, the changes could be within the variability of the method. Indeed, it is not indicated whether the increases in bone-specific alkaline phosphatase (BALP) (9.6%) and C-terminal propeptide of type I procollagen (PICP) (9.9%) were statistically significant compared to baseline after a 3month treatment with SrR. Previous studies have shown that treatment with SrR was associated with statistically significant decreases in the concentrations of total aminoterminal propeptide of type I collagen and C-telopeptide cross-links (S-CTX) from baseline [2–4], a finding that is consistent with a weak anti-remodelling activity of this drug [2]. The hypothetical bone-forming effect of SrR would be better demonstrated by comparing the changes in bone markers induced by this drug, with those observed in the pooled placebo-treated patients of the trials included in the analysis, but these data are missed in the paper. The comparison of the response of PICP between the SrR and the placebo groups would be of special interest A reply to this letter can be found at doi 10.1007/s00198-009-1156-y