Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis.

The effects of anabolic medications (teriparatide [TPTD] and parathyroid hormone [PTH]) differ in patients who have received recent treatment with potent antiresorptives. This perspective reviews studies evaluating bone density (BMD) and histomorphometric effects of treatment sequences beginning with TPTD/PTH followed by potent antiresorptives and those beginning with potent antiresorptives followed by switching to or adding TPTD. Effect of treatment sequence on spine BMD outcome is minor, with modest quantitative differences. However, when individuals established on potent bisphosphonates are switched to TPTD, hip BMD declines below baseline for at least the first 12 months after the switch to TPTD. This transient hip BMD loss is more prominent when the antiresorptive is denosumab; in this setting, hip BMD remains below baseline for almost a full 24 months. In a controlled comparison of those who switched from alendronate to TPTD versus those who added TPTD to ongoing alendronate, the effect on hip BMD was improved with combination therapy. Furthermore, hip strength improved with the addition of TPTD to ongoing alendronate, whereas it was neutral after switching from alendronate to TPTD, primarily due to the effect on cortical bone. Bone biopsy studies indicate that TPTD stimulates bone formation in patients who have not been treated previously as well as in patients on prior and ongoing bisphosphonates. Histomorphometric evidence suggests that use of alendronate with TPTD blocks the TPTD-induced increase in cortical porosity. When possible, we suggest anabolic therapy first, followed by potent antiresorptive therapy. The common practice of switching to TPTD only after patients have an inadequate response to antiresorptives (intercurrent fracture or inadequate BMD effect) is not the optimal utilization of anabolic treatment. In fact, this may result in transient loss of hip BMD and strength. In this setting, continuing a potent antiresorptive while starting TPTD might improve hip outcomes.