Background: Recent real-world evidence is lacking regarding the initiation of bone-targeting agents (BTAs), and time to treatment with BTAs after a diagnosis of bone metastasis secondary to solid tumors (BM-ST) or multiple myeloma (MM), in both the commercially insured and Medicare Supplemental populations. Methods: Patients aged >18 and newly diagnosed with BM-ST or MM during 11/1/2016-6/30/2019 (earliest diagnosis = index date) were selected from the IBM MarketScan Commercial and Medicare Databases. Patients were continuously enrolled in the 12 months before and 6 months after the index date and had no prior evidence of BTA use, skeletal-related events (SREs), osteoporosis or Paget’s disease. Initiation of and time to BTA treatment (i.e., denosumab, zoledronic acid, ibandronate or pamidronate) were reported during the variable follow-up period. SREs prior to BTA use were reported and included spinal cord compression, pathological fractures, surgery and radiation to bone. Results were stratified by tumor type (BM-ST and MM) and payer (commercial and Medicare). Results: The analysis included 8,769 commercially insured patients (70% BM-ST and 30% MM [mean age 55 and 54]) and 4,100 Medicare patients (74% BM-ST and 26% MM [mean age 76 and 75]). Across payers, the most common comorbidities were pain and hypertension. BTA initiation for BM-ST and MM patients was 46% and 24% among the commercial cohort, and 33% and 18% among the Medicare cohort. Among BM-ST commercial and Medicare cohorts, respectively, the proportion initiating BTA varied by solid tumor type: 64% and 45% of breast, 43% and 37% of prostate, and 47% and 34% of lung. Mean (SD) time to BTA initiation for BM-ST and MM patients was 3.0 (4.2) and 3.7 (5.2) months for the commercial cohort, and 3.1 (4.7) and 2.9 (3.3) months for the Medicare cohort. Among patients with BTA initiation, the proportion of BM-ST and MM patients with SREs prior to BTA treatment was 33% and 31% for the commercial cohort and 23% and 26% for the Medicare cohort. Across payers, the majority of first SREs were radiation to bone for BM-ST patients and pathological fracture for MM patients. Conclusions: For commercial patients, about one-half of BM-ST patients and a quarter of MM patients initiated BTA treatment; for Medicare patients, these proportions decreased to a third and a fifth, respectively. On average, BTA initiation occurred within about 3 to 4 months from first diagnosis. The proportion of commercial and Medicare patients with SREs prior to BTA initiation was a third and a quarter, respectively. Results generated from this study should be supplemented by the evaluation of the relationship between bone protection treatment patterns and outcomes associated with BM-ST and MM.