OBJECTIVE: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake. METHODS: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos. RESULTS: To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not. CONCLUSION: We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.