Can you switch from denosumab to teriparatide? Exploring the Risks and Sequential Therapy for Osteoporosis

October 10, 2025 •

4 min read

According to the DATA-Switch study, postmenopausal women with osteoporosis who switched from denosumab to teriparatide experienced transient bone loss. The question, Can you switch from denosumab to teriparatide? involves understanding the profound differences between these medications and the significant risks associated with an abrupt transition without an appropriate bridging agent.

Quick Summary

Directly switching from the anti-resorptive denosumab to the anabolic teriparatide for osteoporosis can trigger rapid bone loss and increase fracture risk. The proper sequence and careful transition management are essential for treatment success.

Key Points

Direct Switch is Risky: Switching directly from denosumab (Prolia) to teriparatide (Forteo) is not recommended due to the high risk of rapid bone loss and multiple vertebral fractures.
Denosumab Rebound Effect: Discontinuation of denosumab leads to a potent and rapid rebound increase in bone turnover, causing a reversal of bone gains.
Teriparatide Cannot Mitigate Rebound: Teriparatide, a bone-forming agent, is not effective at suppressing the accelerated bone resorption that occurs when denosumab is withdrawn.
Proper Sequencing is Key: The optimal sequence for many patients is teriparatide first, followed by denosumab, which leads to cumulative BMD increases.
Bridge with a Bisphosphonate: The recommended strategy for stopping denosumab is to use a potent bisphosphonate, such as zoledronic acid, to block the rebound effect.
Importance of Clinical Oversight: Any transition involving these powerful medications must be managed by a healthcare provider with close monitoring of bone turnover and density.

Understanding the Different Mechanisms: Denosumab vs. Teriparatide

To understand why the sequence of osteoporosis medication matters, it is crucial to recognize how denosumab (Prolia) and teriparatide (Forteo) function differently. Their opposing mechanisms have a significant impact on bone remodeling, the process of old bone being replaced with new bone.

How Denosumab Works

Denosumab is an anti-resorptive medication. It is a monoclonal antibody that targets and inhibits a protein called RANKL. By blocking RANKL, denosumab prevents the formation and function of osteoclasts, which are the cells responsible for breaking down bone. This action effectively slows down the rate of bone resorption, leading to increased bone mineral density (BMD) and reduced fracture risk. The anti-resorptive effect of denosumab, however, is not permanent and is rapidly reversed upon discontinuation of the medication.

How Teriparatide Works

In contrast, teriparatide is an anabolic medication, meaning it helps build new bone. It is a recombinant form of parathyroid hormone that stimulates osteoblasts, the cells responsible for forming new bone tissue. Unlike anti-resorptive agents that slow down bone loss, teriparatide actively promotes bone formation, which can lead to significant increases in BMD, particularly in the spine. Because teriparatide's effect is reversed once treatment is stopped, it is typically followed by a long-term anti-resorptive agent to preserve the bone mass gained.

The High Risk of Switching from Denosumab to Teriparatide

Studies have demonstrated that transitioning directly from denosumab to teriparatide carries significant risks, primarily due to the potent and rapid rebound effect that occurs when denosumab is stopped. This rebound leads to a surge in bone remodeling activity that can negate the bone-building efforts of teriparatide.

The Denosumab Withdrawal Effect

Upon discontinuation of denosumab, the inhibition of RANKL is lifted, causing a powerful and synchronized activation of osteoclasts. This leads to a spike in bone turnover markers, a rapid loss of the BMD gained during treatment, and a heightened risk of multiple vertebral fractures. This rebound phenomenon is the main reason why a direct transition to teriparatide is problematic.

The DATA-Switch Study Findings

The pivotal DATA-Switch study highlighted the consequences of this specific sequencing. The trial involved postmenopausal women with osteoporosis who were transitioned between denosumab and teriparatide after two years of initial treatment. The results were clear and impactful:

Switching from denosumab to teriparatide: Patients in this group experienced transient bone loss at the spine and hip, and progressive bone loss at the radius. The anabolic effect of teriparatide was not sufficient to counteract the high bone resorption rate following denosumab withdrawal.
Switching from teriparatide to denosumab: In contrast, women who switched from teriparatide to denosumab continued to gain BMD, with significant increases at all measured sites. This sequence demonstrated continued therapeutic benefit.

Clinical Implications and Expert Consensus

Experts now recommend against transitioning directly from denosumab to teriparatide. Instead, a potent anti-resorptive agent, most commonly zoledronic acid, should be used as a bridging therapy to prevent the rebound effect and associated vertebral fractures that occur when denosumab is discontinued. Failure to do so can result in serious harm to the patient.

The Critical Role of Proper Sequencing

The order in which anti-resorptive and anabolic therapies are administered is paramount to optimizing treatment outcomes and minimizing risks in osteoporosis management. The following table summarizes the different outcomes based on the sequencing of denosumab and teriparatide.

Comparison of Denosumab and Teriparatide Treatment Sequences


Feature	Teriparatide Followed by Denosumab	Denosumab Followed by Teriparatide	Denosumab Discontinued (No Follow-on)
Effect on BMD	Continues to increase	Results in progressive or transient bone loss	Rapid BMD loss, reversal of gains
Effect on Bone Turnover	Initial increase with teriparatide, followed by suppression with denosumab	Rebound increase in bone turnover above baseline levels	Rebound increase in bone turnover above baseline levels
Fracture Risk	Low risk, continued fracture reduction	Increased risk of multiple vertebral fractures	High risk of multiple vertebral fractures
Clinical Recommendation	Recommended sequence to maximize BMD gains	Avoided sequence due to safety and efficacy concerns	Never recommended; requires follow-on therapy
Bridging Therapy	Not required for this sequence	Requires a potent bisphosphonate like zoledronic acid	Requires follow-on anti-resorptive therapy

Recommended Strategy and Monitoring

When transitioning off denosumab, careful planning and close monitoring are essential to prevent the rebound bone resorption and fracture risk. The recommended approach is to 'hand off' from denosumab to a different class of anti-resorptive medication.

Steps for Transitioning off Denosumab

Choose an Appropriate Follow-On Agent: A potent bisphosphonate, such as intravenous zoledronic acid or oral alendronate, is the most common and effective option to mitigate the bone loss after denosumab discontinuation. Teriparatide is generally not considered an appropriate first choice for this transition.
Administer a Bridge Dose: The follow-on anti-resorptive agent should be administered at the correct time, typically six months after the last denosumab injection, to block the impending rebound bone turnover.
Monitor Bone Turnover Markers and BMD: Healthcare providers should monitor biochemical markers of bone turnover and BMD to assess the effectiveness of the bridging therapy and ensure that bone resorption is adequately suppressed.

Why the Order Matters: A Concluding Thought

In the complex landscape of osteoporosis treatment, the order of medication plays a critical role. While it may seem logical to follow an anti-resorptive with an anabolic agent to build new bone, the specific pharmacology of denosumab makes this sequence highly problematic and dangerous. The rapid withdrawal effect of denosumab requires a different, potent anti-resorptive bridging strategy to maintain bone gains and prevent multiple vertebral fractures. Patients and clinicians must work together to create a carefully sequenced treatment plan to ensure the best possible long-term outcomes for skeletal health. Based on clinical evidence from studies like DATA-Switch, the answer to "Can you switch from denosumab to teriparatide?" is a definitive no, without a bridging agent.

For more detailed clinical information on the management of denosumab discontinuation, consult guidelines from professional organizations such as the American College of Rheumatology, which emphasize careful planning and risk mitigation.

Frequently Asked Questions

Stopping denosumab abruptly leads to a rebound in bone turnover, where osteoclast activity rapidly increases beyond pre-treatment levels. This can cause a swift and significant loss of bone mineral density (BMD) and raises the risk of multiple new vertebral fractures.

Teriparatide is an anabolic agent that stimulates the formation of new bone, while denosumab is an anti-resorptive agent that prevents bone breakdown. The opposite mechanisms of action mean they affect bone remodeling in fundamentally different ways, making the sequence of treatment critical.

The standard of care involves using a potent bisphosphonate, like zoledronic acid (intravenous) or alendronate (oral), as a bridging therapy when discontinuing denosumab. This helps to prevent the rapid increase in bone resorption.

Yes, but the effect may be less robust. Studies show that teriparatide treatment after prior bisphosphonate use can still increase BMD, though the gains might be smaller than in treatment-naive patients. This is a clinically acceptable sequence.

The DATA-Switch study found that patients switching from denosumab to teriparatide experienced transient bone loss at the spine and hips, and progressive loss at the forearm. In contrast, those switching from teriparatide to denosumab continued to gain bone mineral density.

During a transition off denosumab, close monitoring of bone mineral density (BMD) and bone turnover markers is recommended to ensure the rebound effect is mitigated and bone health is protected.

Timing is crucial because the anti-resorptive effects of denosumab fade relatively quickly after the last injection. Starting a bridging bisphosphonate at the appropriate time—typically around six months after the last denosumab dose—is necessary to capture the window of opportunity to prevent the rebound effect.