Summary: In Denmark, osteoporosis treatment is either handled by general practitioners or at more resource demanding specialist clinics. We evaluated the treatment adherence and persistence in the two settings, which were overall similar. The type of medical support did, however, differ and was provided to two very different patient populations. Purpose: The study aimed to investigate the effect of patient care by general practitioners (GPs) or specialists on treatment adherence among osteoporosis patients initiating treatment with oral bisphosphonates (OB). Methods: Dual-energy X-ray absorption (DXA)-scanning data from 2005 to 2013 were extracted. Treatment naïve patients with a T-score ≤ − 2.5 (spine or hip) were included. Information on medical treatment, comorbidities, and socio-economic status was extracted from Danish registries. Scanning results were evaluated by a specialist. Subsequent treatment initiation and follow-up was either handled by GPs or specialists: GP population (GPP) vs. specialist population (SP). Primary adherence was defined as treatment initiating within 12 months from diagnosis and secondary adherence as days with medicine possession rates (MPR) > 80%. Results: Of 11,201 DXA-scanned patients, 3685 met the inclusion criteria (GPP = 2177, SP = 1508). The GPP consisted of relatively more men, was older, had shorter education, lower income, and more comorbidities. There was no difference in baseline T-score or prior incidence of major osteoporotic fractures (MOFs). The GPP was primarily treated with OB and had better primary adherence (adjusted OR_GPP/SP = 1.52 [1.31–1.75], p < 0.0001) than the SP that to a higher degree received another treatment. Secondary adherence was similar (adjusted OR_GPP/SP: OR_{12 months} = 1.02 [0.83–1.26]; OR_{24 months} = 0.90 [0.73–1.10]; OR_{4 years} = 0.88 [0.71–1.07]; OR_{5 years} = 0.91 [0.74–1.13]. Conclusion: Patients in care of specialists were most likely to receive a treatment other than OB. Primary adherence was highest in the GPP, whereas short- and long-term persistence was similar for up to 5 years whether treated by a specialist or a GP.