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Objective: We compared the mid-term efficacy and safety of anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device for cervical degenerative disc disease (CDDD) with and without osteoporosis., Methods: We performed a retrospective study of elderly patients with CDDD treated by single-level ACDF with a Zero-Profile device. The patients were divided into group A (osteoporosis) and group B (no osteoporosis) according to the bone mineral density. The clinical outcomes (Japanese Orthopaedic Association, neck disability index, visual analog scale, and short-form 36 scores), radiological outcomes (cervical lordosis and fusion rate), and complications were reviewed at each follow-up examination., Results: All procedures were successfully performed in all patients. The Japanese Orthopaedic Association, neck disability index, visual analog scale, and short-form 36 scores and cervical lordosis were significantly improved postoperatively in both groups (P < 0.05). However, no significant difference was found between the 2 groups at each follow-up point (P > 0.05). No significant difference was found in the fusion rate at 3 months postoperatively (group A, 88.9%; group B, 90.0%), dysphagia rate at 1 month postoperatively (group A, 11.1%; group B, 15.0%), or cage subsidence rate at the final follow-up visit (group A, 11.1%; group B, 10.0%; P > 0.05). All patients achieved solid fusion, and no patient had dysphagia at the final follow-up examination., Conclusions: ACDF with the Zero-Profile device can be used as an effective and reliable treatment for single-level CDDD with osteoporosis., (Copyright © 2018. Published by Elsevier Inc.)