SAT-776 - Unintended Denosumab Discontinuation and Rebound Fractures: A Retrospective Analysis of Patients with Osteoporosis in A Single Veterans Endocrine Clinic

Background: Discontinuation of denosumab has been associated with an increased risk of rebound vertebral fractures.

Objectives: We aim to review the risks of our veteran patients.

Methods: This was a retrospective study of the patients on denosumab at Kansas City veteran affairs (VA) endocrine clinic between 2017 and 2025. The period of denosumab discontinuation was defined as > 240 days (about 8 months). Demographics, number of doses prior to the lapse, vertebral fractures, exposure to previous osteoporotic medications, the emergency room visits, bone density, non-lapse related contributing factors, reasons of discontinuations and clinical course of osteoporosis diagnosis were reviewed from electronic records. Also, we investigated reasons that could have prevented the rebound vertebral fracture.

Results

95 patients out of 118 were included in the study (76% male, 24% female). 38%(N=36) identified with unintended denosumab lapse of which 3 (8%) had vertebral compression fractures. With risk factors as follows: one 65-year-old female with intermittent /previous exposure to steroid) and 2 males > 75 years with a previous history of vertebral facture. All 3 received 4 or less doses of denosumab and previous bisphosphonate therapy.

Of the 33 patients without rebound fractures, 70% were men, 30% women, with age < /= 64years (9%), 65-74 years (42%); 75 years (49%). Doses of Denosumab before the lapse, 64% < 5 and 36% >5. Prior bone-modifying agents included teriparatide (6%), bisphosphonate (oral 30%, intravenous (IV) 18%, oral followed by IV 15%.

The most common reasons for treatment lapse were logistical barriers: lack of transportation/distance, missed or rescheduled appointments (41%), covid 19 related pandemic related loss of follow up (15%), dental procedures (22%), and social and medical factors (22%).

Discussion/

Conclusion:

At Veterans Affairs we typically see elderly male patients and Denosumab is considered second line agent unless there is history of renal insufficiency. Prior treatment with oral or IV bisphosphonate may render some protection. Being male could be contributing factor that needs to be investigated further. Preexisting vertebral fracture and intermittent steroid exposure probably contribute more than the duration of denosumab use prior to the lapse.

Despite these findings, denosumab treatment lapses remain common in real-world practice and have been associated with increased fracture risk. There is a need for care coordination to identify risk for treatment interruption and early intervention. Identifying patients who are at high risk for rebound fracture is essential before initiating denosumab treatment. Considering alternative treatment options when available in these high-risk patients could minimize the rebound fracture risk.

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