Letter to the Editor: “Comparison of Teriparatide and Denosumab in Patients Switching from Long-Term Bisphosphonate Use”

In a retrospective cohort analysis of 215 patients, Lyu and colleagues (1) reported that patients who switched from bisphosphonate (BP) to denosumab had a greater increase in total hip (TH) and femoral neck (FN) bone mineral density (BMD) than those who switched from BP to teriparatide. Based on changes in BMD at the TH (transient loss of 1%) and FN (unchanged after 1 year followed by a 2% increase after 2 years of teriparatide therapy), they concluded that “among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.” Fracture data were not reported in their study, except for a comment that fracture risk was low. The authors have overlooked reports from clinical trials of teriparatide in the context of prior long-term BP use with better efficacy results than those in their retrospective analysis. For instance, in the EUROFORS clinical trial, the 2-year increases versus baseline in lumbar spine, TH, and FN BMD were 9.8%, 2.3%, and 3.9%, respectively, in 285 patients who had received prior long-term antiresorptive therapy, mainly (93%) BP (2). An early, transient decrease in FN and TH BMD has been reported in several previous studies of patients switching from BP to teriparatide (3). None of these studies reported significant differences in fracture incidence. Thus, the crucial clinical question not addressed by Lyu and colleagues is whether this early transient decrease in BMD at TH and FN is associated with increased fracture risk. In the 2-year VERO trial, new vertebral and clinical fractures were significantly lower in patients receiving teriparatide than in those receiving risedronate (4). In VERO, 52.6% of patients had been exposed to prior BP, with 39.2% having had recent BP use (5). In the prespecified subgroup analysis, fracture risk reduction on teriparatide versus risedronate was similar in patients with prior BP exposure, including recent BP use, as compared with patients who were osteoporosis-treatment naïve (5), without any increase in the fracture risk during the first months of switching from BP to teriparatide—just the opposite (5). Longitudinal changes in BMD and bone markers were not assessed in VERO. Furthermore, a recent meta-analysis of clinical trials of teriparatide versus placebo or active controls showed a significant 56% reduction in hip fractures on teriparatide (6). It is likely that treatment with osteoanabolic therapies leads to improvements in bone microarchitecture and bone tissue quality above and beyond what is captured by changes in BMD on dual-energy X-ray absorptiometry (7), BMD may not be the most important surrogate marker to evaluate therapeutic response to teriparatide (8). The transient, early loss of TH and FN BMD was not associated with early or 2-year risk of vertebral, clinical, or nonvertebral fractures in any published study. Therefore, according to the VERO data, in managing patients with severe osteoporosis, a switch from BP to teriparatide remains as an effective therapeutic option in the prevention of vertebral and clinical fractures. Whether switching from BP to denosumab would have superior antifracture efficacy to teriparatide in this setting remains unknown. bisphosphonate bone mineral density femoral neck total hip Disclosure Summary: P.G. received consultant and/or speaker fees from Lilly, and research support from Pfizer, Abbott, Lilly, Amgen, MSD, Roche, UCB, BMS, and Novartis. F.M. is an employee and a shareholder of Lilly. D.L.K. received honoraria, research grants, and/or consultant fees from Amgen, Lilly, and UCB.

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