Study finds risk factors for vertebral fractures and bone loss after denosumab discontinuation
Denosumab reduces bone resorption and improves bone mineral density (BMD). A recent study suggests that the age, treatment duration, and prior bisphosphonate therapy are all associated with potential bone mineral density (BMD) loss following the discontinuation of denosumab therapy. The study findings were published in the journal Bone on December 26, 2020.
Unlike bisphosphonates, denosumab is not incorporated into the bone. Therefore, its effect on bone resorption stops after treatment discontinuation. Denosumab discontinuation without subsequent bisphosphonates (BPs) is associated with bone loss and multiple vertebral fractures. However, the risk factors of bone loss and multiple fractures remain unclear. Therefore, researchers of Switzerland conducted a study to identify the risk factors for bone loss and vertebral fractures after denosumab discontinuation.
It was a retrospective study of 219 women with osteoporosis who discontinued denosumab treatment and received subsequent treatment with zoledronate, other BPs or a selective estrogen receptor modulator (SERM), or no therapy. Researchers analyzed the fracture rate, longitudinal bone mineral density (BMD) changes and bone turnover markers (BTMs) within 2years after denosumab discontinuation. They used the linear regression model, to evaluate the loss of BMD and age, BMI (kg/m2), denosumab treatment duration, pre-treatment, prior fracture state, baseline T-scores, use of glucocorticoids or aromatase inhibitors and BMD gains under denosumab therapy.
Key findings of the study were:
♦ Among 219 women, 171 received zoledronate after denosumab discontinuation, 26 had no subsequent treatment and 22 received other therapies (other BPs or a SERM).
♦Upon analysis, researchers found that zoledronate was associated with the fewest vertebral fractures (hazard ratio 0.16), and all subsequent therapies retained BMD at all sites to some extent.
♦ They also found that higher BMD loss was associated with younger age, lower BMI, longer denosumab treatment, lack of prior antiresorptive treatment and BMD gain under denosumab treatment.
♦ They noted that the BTM levels correlated with denosumab treatment duration and bone loss at the total hip but not the lumbar spine.
♦ These findings imply:
- Vertebral fractures after denosumab discontinuation were low with subsequent therapy.
- Pre-treatment with BPs, such as zoledronate, is associated with fewer vertebral fractures.
- Longer denosumab treatment was associated with increased bone loss afterwards.
- Higher BMD gains under treatment correlated with BMD loss upon discontinuation.
The authors concluded, "Compared to no subsequent therapy, zoledronate was associated with fewer vertebral fractures after denosumab. Further, BMD loss depended on denosumab treatment duration, age, prior BP therapy and BMD gain under denosumab therapy, whereas BTM levels were associated with bone loss at the total hip and denosumab treatment duration."
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