The low and disproportionate utilization of antiresorptive therapy in patients with osseous metastasis

Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy.

Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively.

The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35-44 (HR 1.27 [95 % CI 1.08-1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71-1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39-2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13-1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66-0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77-16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15-0.87, all p < 0.001).

The utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy.