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September 27, 2019
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BMD gains can be maintained when switching from denosumab to alendronate

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Postmenopausal women who took denosumab for a year did experienced no significant decrease in bone mineral density after switching to alendronate, according to findings presented at the American Society of Bone and Mineral Research annual meeting.

David L. Kendler

“Denosumab and alendronate are both antiresorptive therapies effective in the treatment of postmenopausal osteoporosis. Their mechanism of action is very different, and our study focuses on sequential therapy,” David L. Kendler, MD, a clinical professor in the division of endocrinology at the University of British Columbia in Vancouver, told Endocrine Today. “Our study demonstrates that after 1 year on denosumab, on average, there is preservation of bone mineral density when patients are switched to weekly alendronate. Therefore, the declines in bone density, which would otherwise be seen, can be prevented.”

Kendler and colleagues analyzed data from 126 postmenopausal women (mean age, 65 years) who were randomly assigned to a year of a 60 mg denosumab (Prolia, Amgen) regimen followed by a year of a 70 mg alendronate regimen as part of the Denosumab Adherence Preference Satisfaction study. At baseline, all participants had T-scores between –2 and –4 at the lumbar spine, total hip and femoral neck, but none had been treated for osteoporosis before the study.

The researchers measured BMD at baseline and 12 and 24 months. Participants who experienced a 3% or greater increase in BMD were considered to have a significant increase in BMD while participants who experienced a decrease of more than 3% were considered to have a significant decrease in BMD. All other participants were considered to have maintained BMD.

Osteoporosis consultation with older woman 2019 
Postmenopausal women who took denosumab for a year did experienced no significant decrease in bone mineral density after switching to alendronate.
Source: Adobe Stock

After the year of denosumab treatment, the researchers observed a mean 5.6% increase in BMD at the lumbar spine compared with baseline. In the year of alendronate treatment, the researchers observed a mean 0.6% increase in lumbar spine BMD compared with measurements taken at 12 months. Lumbar spine BMD following denosumab treatment was maintained by 63.4% of participants after alendronate treatment.

The researchers also observed a mean 3.2% increase in BMD at the total hip after the year of denosumab treatment, compared with baseline. During alendronate treatment, the researchers observed an additional mean 0.4% increase in total hip BMD. Total hip BMD following denosumab treatment was maintained by 81.5% of participants after alendronate treatment.

At the femoral neck, there was a mean 3.1% increase in BMD after a year of denosumab treatment compared with baseline. In the following year with alendronate treatment, there was an additional 0.1% decrease in femoral neck BMD. In total, femoral neck BMD achieved during denosumab treatment was maintained by 60.9% of participants after alendronate treatment.

However, Kendler also noted that “patients with the greatest increase in BMD on denosumab in the first year were at risk for the greatest declines in BMD on alendronate in the second year.”

“This may be a feature of ‘regression to the mean,’” Kendler said. “This is an artifact of imprecision of BMD measurements. It may also relate to patients whose bone turnover is highest having the greatest BMD response to denosumab’s antiresorptive effect. When denosumab is discontinued, this higher endogenous bone turnover may be incompletely suppressed by alendronate resulting in bone loss. We had hoped that there would be other predictors of bone loss on switching to alendronate, which would be clinically helpful. The lack of other predictors means that following bone density a year after switching to alendronate would be prudent.” – by Phil Neuffer

Reference:

Kendler D, et al. Abstract 1047. Presented at: American Society of Bone and Mineral Research; Sept. 20-23, 2019; Orlando.

For more information:

David L. Kendler, MD, can be reached at davidkendler@gmail.com.

Disclosures: This study was sponsored by Amgen. Kendler reports he has received grant and/or research support from Amgen, AstraZeneca, and Eli Lilly and has served as a consultant, served on the speakers bureau and performed advisory activities for Amgen, Eli Lilly and Pfizer.