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Transition to denosumab monotherapy after combination results in favorable BMD changes
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Postmenopausal women with osteoporosis who switched from combination denosumab therapy to denosumab monotherapy experienced the most favorable total and cortical volumetric bone mineral density changes compared with switching from denosumab to teriparatide or from teriparatide to denosumab.
Joy N. Tsai, MD, of the endocrine unit at Massachusetts General Hospital, and colleagues evaluated data from 679 postmenopausal women with osteoporosis to determine the effect on BMD of switching from teriparatide (Forteo, Eli Lilly) to denosumab as part of the DATA-Switch HR-pQCT study.
In the first 24 months of the study, participants were randomly assigned to teriparatide 20 µ daily, denosumab 60 mg every 6 months or both. During the 24-month extension period, participants who had received teriparatide were switched to denosumab, participants who had been assigned to denosumab received teriparatide, and participants assigned to both received denosumab monotherapy.
High-resolution peripheral quantitative CT (HR-pQCT) at the distal tibia and radius was used to assess the effects on BMD of switching medication.
The combination-to-denosumab group experienced greater increases in total volumetric BMD at the tibia over 48 months (5.8%) compared with the teriparatide-to-denosumab group (3.3%) and the denosumab-to-teriparatide group (-1.1%).
Cortical BMD at the tibia continued to increase over 48 months by 3.1% in the combination-to-denosumab group whereas no change was observed in the teriparatide-to-denosumab group and a decrease was seem in the denosumab-to-teriparatide group (-3.7%).
Cortical porosity at the tibia increased more in the denosumab-to-teriparatide group (16.2%) compared with the teriparatide-to-denosumab group (7.2%) and the combination-to-denosumab group (-3.4%). Stiffness at the tibia increased more in the combination-to-denosumab group (4.9%) over the 48 months compared with the teriparatide-to-denosumab group (3.1%) and denosumab-to-teriparatide group (-0.1%).
The combination-to-denosumab group experienced greater increases in total volumetric BMD at the radius at 48 months (5.1%) compared with the teriparatide-to-denosumab group (0.5%; P = .016) and the denosumab-to-teriparatide group (-3.3%; P < .001).
Cortical volumetric BMD at the radius increased only in the combination-to-denosumab group (2.4%) whereas it decreased in both the teriparatide-to-denosumab group (-0.8%; P = .003) and the denosumab-to-teriparatide group (-3.4%; P < .001).
Over the 48 months, cortical porosity at the radius increased the most in the denosumab-to-teriparatide group (45.6%) compared with the teriparatide-to-denosumab group (31.9%) and the combination-to-denosumab group (24.8%). Stiffness at the radius increased the most in the combination-to-denosumab group (3.3%) compared with the teriparatide-to-denosumab group (0.2%) and the denosumab-to-teriparatide group (-1.2%).
There were no significant differences between the groups for changes in trabecular microarchitecture at the tibia or radius.
“These results strengthen our emerging understanding of the importance of the sequence of antiresorptive and anabolic therapy, particularly as it relates to these specific medications,” the researchers wrote. “In particular, our findings demonstrate that transitioning patients from denosumab to teriparatide stimulates progressive detrimental changes in cortical density and structure at the tibia and radius, which, in turn, decrease stiffness at these sites. As such, even in the absence of fracture-efficacy data, these findings support the concept that physicians should avoid transitioning patients from denosumab directly to teriparatide. Additionally, this study continues to reinforce the potential of combined denosumab/teriparatide therapy to durably improve skeletal integrity in postmenopausal osteoporotic women and supports the consideration of such an approach in those at the greatest risk of fragility fracture.” – by Amber Cox
Disclosure: Tsai reports serving on an advisory board for Amgen. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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This study confirms the DXA results from the same cohort: Following teriparatide treatment with denosumab seems to be a good idea; following denosumab with teriparatide is not. Teriparatide produces its main anabolic effect by stimulating bone formation that follows bone resorption. Because denosumab reduces bone turnover, it is not surprising that some amount of time after discontinuation of denosumab is required before teriparatide starts to work (the DXA results showed, after changing from denosumab to teriparatide, loss in the spine for 6 months and in the hip for 12 months before gains began to appear).
This is extremely important information that I hope is noted by insurers. Many of them refuse to authorize treatment with teriparatide unless the patient has first failed denosumab. This and other studies show why that is not a good idea.
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