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Comparative outcomes of denosumab and zoledronic acid discontinuation in hip fracture surgery: a nationwide database
Seok Ha Hong1, Yeon Ju Yu2, Seung Beom Han3
1Department of Orthopedic Surgery, College of Medicine, Korea University Anam Hospital, 73, Inchon-Ro, Seongbuk-Gu, Seoul, 02841, Republic of Korea.
Insights
Discontinuing denosumab (DMAB) after hip fracture surgery significantly raises the risk of vertebral and rib fractures, especially in patients with poor adherence and comorbidities. Maintaining treatment is vital for fracture prevention.
Area of Science:
- Orthopedics
- Pharmacology
- Geriatrics
Background:
- Hip fracture patients often have comorbidities and medication adherence challenges.
- Osteoporosis treatment, including denosumab (DMAB) and zoledronic acid (ZOL), is crucial for preventing secondary fractures.
- Understanding the fracture risks associated with discontinuing these medications is essential for patient management.
Purpose of the Study:
- To evaluate the risk of major osteoporotic and periprosthetic fractures in hip fracture patients who stopped denosumab (DMAB) or zoledronic acid (ZOL).
Main Methods:
- A nationwide South Korean health insurance database analysis included patients aged ≥ 60 years post-hip fracture surgery who initiated DMAB or ZOL.
- 1737 DMAB and 3720 ZOL discontinuers were identified; 3240 patients were matched 1:1 using propensity scores.
- Subsequent fractures after discontinuation were assessed, with discontinuation defined by specific gaps in treatment.
Main Results:
- DMAB discontinuation markedly increased vertebral fracture risk (HR 1.81) and rib fracture risk (HR 2.04) compared to ZOL discontinuation.
- Higher Charlson Comorbidity Index (CCI) scores correlated with increased vertebral (HR 1.05) and rib fracture (HR 1.12) risks.
- No significant differences were found in hip, other nonvertebral, or periprosthetic fracture risks between the groups.
Conclusions:
- Denosumab discontinuation significantly elevates vertebral and rib fracture risks in hip fracture patients with poor adherence and comorbidities.
- Real-world data highlights the importance of optimizing medication adherence to mitigate fracture risk in this population.
- Maintaining treatment continuity is critical for vulnerable patients to prevent further skeletal-related events.
Abstract:
In hip fracture patients with poor medication adherence, DMAB discontinuation significantly increased the risk of subsequent vertebral and rib fractures. Additionally, higher CCI scores were associated with an increased risk of these fractures. These findings underscore the importance of maintaining treatment adherence to minimize fracture risk in this vulnerable population.
Purpose:
To assess the risk of major osteoporotic fractures and periprosthetic fractures in hip fracture patients who discontinued denosumab (DMAB) or zoledronic acid (ZOL).
Methods:
Data from the South Korean National Health Insurance Review and Assessment Service were analyzed, focusing on patients aged ≥ 60 years who underwent hip fracture surgery and initiated DMAB or ZOL treatment. Among 20,180 patients, 1737 discontinued DMAB, and 3720 discontinued ZOL. After 1:1 propensity score matching, 3240 patients were included in the final analysis. The DMAB group was stratified into three subgroups based on the cumulative DMAB duration after hip fracture surgery: 1-2, 2-3, and > 3 Y. Discontinuation was defined as a 270-day gap for DMAB or 540-day gap for ZOL last injections. Subsequent osteoporotic fractures after discontinuation were evaluated.
Results:
DMAB discontinuation significantly increased the risk of subsequent vertebral fractures (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.28-2.56, P = 0.01) and rib fractures (HR = 2.04; 95% CI, 1.27-3.23, P = 0.004) compared to ZOL discontinuation. Higher Charlson Comorbidity Index (CCI) scores were also significantly associated with an increased risk of subsequent vertebral (HR 1.05, 95% CI 1.03-1.09, P = 0.02) and rib fractures (HR 1.12, 95% CI 1.06-1.19, P < 0.01). Although the incidence of hip fractures was lower in DMAB discontinuation group (1 case) than in the ZOL discontinuation group (10 cases), this difference did not reach statistical significance. No significant difference was observed in the risk of other nonvertebral fractures (humerus, wrist, ankle) and periprosthetic fracture between the two groups.
Conclusion:
This nationwide study, the first to use real-world data, highlighted the significant increase in the risk of vertebral and rib fracture associated with DMAB discontinuation in patients with poor adherence and higher comorbidity burden. Optimizing medication adherence is crucial to minimize the fracture risk in this vulnerable population.
Level Of Evidence:
Level III, Prognostic.
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