Effects of Denosumab and Teriparatide Transitions on Bone Microarchitecture and Estimated Strength: the DATA-Switch HR-pQCT study.

In postmenopausal osteoporosis, switching from teriparatide to denosumab results in continued bone mineral density (BMD) gains whereas switching from denosumab to teriparatide results in BMD loss. To assess the effects of these transitions on bone microarchitecture and strength, we performed high-resolution peripheral QCT (HR-pQCT) at the distal tibia and radius in postmenopausal osteoporotic women who received 24 months of teriparatide 20 μg daily followed by 24 months of denosumab 60 mg every 6 months, 24 months of denosumab followed by 24 months of teriparatide, or 24 months of both medications followed by 24 months of denosumab. The 77 women who completed at least one post-switch visit are included in this analysis. Tibial cortical volumetric BMD (vBMD) increased between months 24 and 48 in the teriparatide-to-denosumab (net 48-month change -0.8% ± 2.4%) and combination-to-denosumab groups (net 48-month changes +2.4% ± 4.1%) but decreased in the denosumab-to-teriparatide group (net 48-month change -3.4% ± 3.2%, p < 0.001 for all between-group comparisons). Changes in total vBMD, cortical thickness, and estimated stiffness (by micro-finite element analysis [µFEA]) followed a similar pattern, as did changes at the radius. Conversely, tibial cortical porosity remained stable between months 24 and 48 in the teriparatide-to-denosumab and combination-to-denosumab groups (net 48-month changes +7.2% ± 14.8% and -3.4% ± 12.1%, respectively) but increased in the denosumab-to-teriparatide group (net 48-month change +16.2% ± 11.5%, p < 0.05 versus other groups). Trabecular vBMD changes did not differ among groups. Together, these findings demonstrate that in women treated with denosumab, switching to teriparatide is associated with a reduction in total and cortical vBMD, cortical thickness, and estimated strength, whereas switching to denosumab from teriparatide or combination therapy results in improvements in these parameters with the greatest improvements observed in women treated with combined therapy followed by denosumab. These findings strongly suggest that the use of teriparatide after denosumab should be avoided and that the use of combined teriparatide/denosumab followed by denosumab alone may be a useful treatment strategy in those with severe osteoporosis.