Abstract Disclosure: A. Khan: None. B.P. Ramchandani: None. R.A. Zielinski: None. J. Liu: None. F.S. Mirza: None. Introduction: Discontinuation of denosumab (Dmab) results in rebound increase in bone turnover and increased risk of vertebral fracture. Guidelines recommend that discontinuation of denosumab should be followed by an oral or intravenous bisphosphonate (BP), hormone therapy or selective estrogen receptor modulator (SERM). Hypothesis: We hypothesize that patients who received weekly alendronate (ALEN) after discontinuation of Dmab will have less of a decline in bone mineral density (BMD) compared to patients who received once yearly zoledronic acid (ZA). Methods: We conducted a retrospective chart review to compare the change in BMD and factors affecting BMD loss in patients who received sequential therapy with ZA versus ALEN. IRB approval was obtained. Patients were selected using Epic SlicerDicer if they had taken Dmab therapy from 2018 (year of epic implementation) onwards and had been transitioned to a BP. A total of 251 patients were initially selected. 35 patients met the inclusion criteria of being transitioned off to ALEN or ZA at least 1 year prior to date of data acquisition; 21 transitioned to ZA and 14 to ALEN. The rest of the patients were continuing Dmab and excluded from the analysis. BMD gain after Dmab therapy was evaluated. BMD change after 1 year of receiving sequential therapy was compared between the two groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Results: A total of 35 patients were included in data analysis with mean age of 73.7 + 9 years. The mean percentage gain in BMD achieved after Dmab therapy was 9.9 + 8.5%, 4.6 + 10.6%, and 6 + 5.2% at the LS, FN and TH respectively. The mean duration of Dmab therapy was 4.4 + 2.1 years. One year following sequential therapy, mean percentage BMD loss at the LS was 4.5% with ALEN and 3.0% with ZA (p-value: 0.59, 95% CI: -0.04 to 0.08). Following sequential therapy, mean percentage loss at FN was 2.2% with ALEN and 0.2% with ZA (p-value: 0.1895% CI: (-0.01 to 0.04), mean percentage loss at TH was 2.0 % with ALEN and 2.2% with ZA (p-value: 0.78, 95% CI: -0.03 to 0.02). Mean vitamin D level of all patients at time of starting sequential therapy was 45.9 + 12.9 ng/ml. Duration of prior bisphosphonate use before starting Dmab therapy did not have any significant effect on BMD loss after sequential therapy. All patients had vitamin D level in a good range at the beginning and end of the study period. Conclusion: There is invariably some decline in BMD when transitioning from Dmab to BPs. Although our data showed somewhat greater BMD loss at LS and FN with ALEN compared to ZA, this difference was not statistically significant and failed to reject the null hypothesis. These findings need to be evaluated further in larger prospective studies. Presentation: 6/3/2024