Romosozumab is a humanized, anti-sclerostin monoclonal antibody used to treat osteoporosis, which increases bone formation and decreases bone resorption. It enhances fracture healing and systemic romosozumab administration may have therapeutic potentials for accelerating bone healing of even nonunion. Herein, a 61-year-old heavy smoker male with distal radius nonunion who achieved successful bone union by combination therapy of romosozumab and spanning distraction plate fixation with bone graft substitutes was presented. Through the dorsal approach, atrophic comminuted nonunion of the distal radius was sufficiently debrided. Reduction of the distal radius was performed using indirect ligamentotaxis, and a 14-hole locking plate was fixed from the third metacarpal to the radial shaft. A beta (β) tricalcium phosphate block was mainly packed into the substantial metaphyseal bone defect with additional bone graft from the resected ulnar head. Postoperatively, systemic administration of monthly romosozumab was continued for six months. Complete bone union was achieved 20 weeks postoperatively and the plate was, then, removed. Wrist extension and flexion improved to 75o and 55o, respectively, without pain, and grip strength increased 52 weeks postoperatively from 5.5 kg to 22.4 kg. During romosozumab treatment, bone formation marker levels increased rapidly and finally returned to baseline, and bone resorption marker levels remained low. In conclusion, combination of systemic romosozumab administration and grafting β-tricalcium phosphate with bridge plating provides an effective treatment option for difficult cases of comminuted distal radius nonunion with risk factors such as smoking, diabetes, and fragility.