About the Comparison of Two Anabolic Agents, Teriparatide and Strontium Ranelate, in Treated Osteoporotic Women

To the Editor: We would like to comment on the article “Comparative Effects of Teriparatide and Strontium Ranelate on Bone Biopsies and Biochemical Markers of Bone Turnover in Postmenopausal Women With Osteoporosis” by Recker et al., which has recently been published in the JBMR.1 This study set out to show the superiority of teriparatide over strontium ranelate on bone histomorphometric parameters. However, there are several important limitations in this paper that need to be considered. First, there is a clear imbalance in the baseline characteristics of the 79 patients randomized, to the disadvantage of the strontium ranelate group. Indeed, this group had a lower vitamin D status than the teriparatide group (serum 25-hydroxyvitamin D, 68.5 ± 33.0 versus 79.8 ± 53.7 nM, respectively). In addition, there were more patients with previous treatment with hormone replacement therapy (HRT) or calcitonin in the strontium ranelate group than in the teriparatide group (12.5% versus 2.6%, respectively). These important differences are not discussed by the authors despite the fact that they could have had a dramatic impact on bone status and bone remodeling in the strontium ranelate group. In addition, the authors failed to give information on compliance with strontium ranelate, notably in terms of blood strontium content, which is an indirect assessment of compliance for this agent. Second, the authors report that there was no difference in osteoblast surface (Ob.S) between the teriparatide and strontium ranelate groups. Additionally, there was no significant difference in parameters related to bone structure between the two treatment groups, with the exception of cortical porosity, which was significantly increased in the teriparatide group (p = 0.037). Increased cortical porosity is a potential issue for bone quality and needs to be taken very seriously. Surprisingly, the authors interpreted these data as evidence of a limited anabolic effect of strontium ranelate in these patients. Furthermore, the authors made positive statements on the basis of nonsignificant results. For instance, the authors presented differences in histomorphometric parameters in a favorable way for teriparatide, even though the differences between strontium ranelate and teriparatide were not statistically significant. A typical example is “Although not statistically significant, the majority of the bone formation parameters in the teriparatide group were numerically greater than in the SrR group.” Such an interpretation lacks scientific basis and may be misleading for the reader. Given the lack of significant difference in the histomorphometric parameters between the two treatments, a more consistent interpretation of these data are that teriparatide and strontium ranelate have similar anabolic effects on bone microarchitecture. These data support previous studies in postmenopausal osteoporosis2 and in appropriately designed preclinical studies in animals3, 4 showing that strontium ranelate improves bone mass and microarchitecture in vivo, as revealed by histomorphometric analyses. This, however, does not preclude that teriparatide and strontium ranelate may have different amplitudes of effect and distinct mechanisms of action on bone-forming cells.