Why is the sequence of Denosumab followed by Teriparatide not recommended in osteoporosis management?

Created/Updated: #jun2025

Research by : Perplexity
Edited by: Dr. Om J Lakhani

Introduction

Switching from denosumab to teriparatide in the management of osteoporosis is not generally considered the optimal therapeutic sequence, and evidence suggests it may be associated with significant risks and suboptimal outcomes compared to other transitions.

Evidence on Switching from Denosumab to Teriparatide

Bone Mineral Density (BMD) and Bone Loss:
Multiple studies have shown that switching from denosumab to teriparatide results in transient bone loss at the spine and hip, as well as progressive bone loss at the radius shaft2 4 5. This is in contrast to switching from teriparatide to denosumab, which leads to further increases in BMD at all measured sites.
Bone Turnover Markers:
Transitioning to teriparatide after denosumab causes a marked and sustained increase in bone resorption and formation markers (e.g., CTX and osteocalcin), exceeding the levels seen with teriparatide alone, which may indicate accelerated bone remodeling and potential instability2 5.
Impact on Bone Microarchitecture:
Switching from denosumab to teriparatide can transiently degrade spine trabecular microarchitecture, as measured by trabecular bone score (TBS)4. The clinical consequences of this effect require further study, but it raises concerns about bone quality and stability.
Fracture Risk:
The accelerated bone remodeling and BMD loss observed with this transition may increase the risk of fractures, especially multiple vertebral fractures, similar to the "rebound effect" seen when denosumab is discontinued without appropriate follow-on therapy5 6.
Expert Consensus:
Current recommendations and expert opinion advise against switching from denosumab directly to teriparatide. If denosumab is discontinued, a bisphosphonate is generally preferred to mitigate the risk of rapid bone loss and vertebral fractures5 6. There are emerging data that romosozumab (another anabolic agent) may be more effective than teriparatide after denosumab, but teriparatide alone is not considered the best choice6.

Summary Table

Transition	Effect on BMD/Microarchitecture	Bone Turnover Markers	Fracture Risk	Consensus
Denosumab → Teriparatide	Transient/progressive bone loss	Markedly increased	Potentially increased	Avoid or use with caution2 5 6
Teriparatide → Denosumab	Further BMD increase	Decreased	Reduced	Recommended2 4
Denosumab → Bisphosphonate	Maintains or increases BMD	Controlled	Reduced	Recommended5 6

Conclusion

Switching from denosumab to teriparatide is associated with adverse effects on BMD, bone microarchitecture, and bone turnover markers, and may increase the risk of fractures. Current consensus and evidence recommend against this transition, favoring the use of a bisphosphonate after denosumab to protect bone health2 5 6. If an anabolic agent is needed, romosozumab may be a better option than teriparatide after denosumab, but more data are needed to confirm this.