Purpose: Although denosumab is a safe and effective treatment for osteoporosis in various clinical trials, few studies have investigated its efficacy in specific clinical situations. The effect of non-compliance with the standard six-month dosing regimen for denosumab on bone mineral density (BMD) was assessed in a retrospective study of patients prescribed denosumab during the COVID-19 pandemic. Patients and Methods: Between February 2019 and September 2020, 638 patient records were reviewed, with 236 patients meeting the eligibility criteria. Patients were divided into three groups: those who received denosumab injections between five and seven months after their initial subcutaneous injection, those who received denosumab injections between seven and nine months after their initial subcutaneous injection, and those who received denosumab injections more than nine months after their initial subcutaneous injection. A multivariate regression study was conducted to compare the BMD shift (at least one year apart) before and after two denosumab injections between the three pre-specified groups in both the lumbar spine (LS) and the femoral neck (FN). Results: The difference between LS BMD indicates that there is a statistical difference between subjects who received denosumab injections between 5 and 7 months (near-standard dosing interval) and more than 9 months (P=0.03), but not in FN BMD, and no clinically significant association was identified. Conclusion: The results of this study show that in special clinical situations, such as the COVID-19 pandemic, clinicians may have some flexibility to prescribe denosumab, but the interval between injections should not exceed 9 months.