Although denosumab (Prolia) has been shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials, few studies have determined its effectiveness in real world clinical practice. A retrospective review of patients prescribed Prolia assessing the impact that noncompliance from the regular dosing regimen of six months for denosumab has on bone mineral density (BMD) was performed. 924 patient records were reviewed between August 2012 and September 2013 with 436 patients meeting the eligibility criteria. Patients were divided into three groups: subsequent injection of denosumab (1) less than five months, (2) between five and seven months, and (3) more than seven months after their initial subcutaneous injection. A multivariable regression analysis was conducted comparing the differences among the three prespecified groups in BMD change (g/cm2) after one year of denosumab therapy at both the lumbar spine (LS) and femoral neck (FN). The differences in LS and FN BMD have shown that the relationship between the timing of drug administration in these three groups and change in BMD over 1 year was not clinically or statistically significant (). A follow-up study with a larger sample size and longer follow-up duration is required to further characterize this relationship.