Safety and Efficacy of rhBMP-2 for Treating Acute Traumatic Fractures of the Upper and Lower Extremities: A Multicenter Prospective Study

Abstract

Background: Delayed or non-union fractures comprise 5-10% of cases, indicating the need for biologic interventions. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent osteoinductive agent; yet, collagen carrier-based uncontrolled release causes adverse events. We evaluated the safety and efficacy of a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system for acute traumatic upper and lower fractures exhibiting bone defects. Methods: This prospective, multicenter, single-arm clinical trial enrolled 90 patients who underwent surgery using a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system (Novosis^TM). Radiographically validated union at 6 and 12 months post-surgery and treatment success (union without additional surgery) were used to assess efficacy. The incidence, type, and severity of all device-related adverse events during follow-up were monitored by investigators to evaluate safety. Results: Of the 90 patients enrolled, 81 were included in the full analysis set. The mean age was 58.5 years, and 18.6% (15/81) had open fractures. At 6 months post-surgery, radiographically validated union was achieved in 81.5% (66/81) of patients, increasing to 96.2% (77/81) at 12 months after surgery. Treatment success was 95.0% (76/81). Adverse events were rare (1/81, 1.2%). No ectopic ossification, systemic complications, or severe inflammatory responses were observed. Conclusions: HA-based rhBMP-2 intervention demonstrated favorable union rates and safety with minimal complications in acute upper and lower fractures with bone defects. The biocompatibility and controlled-release properties of HA likely improved efficacy and reduced complications. Results should be interpreted as feasibility data from a heterogeneous case series without a control group. Larger randomized controlled comparative trials are warranted for optimal dosing and evaluating efficacy and cost-effectiveness.

Keywords: bone morphogenetic protein-2; bone regeneration; fracture; hydroxyapatite; trauma.

Figure 1

Surgical implementation of hydroxyapatite-carrier rhBMP-2. (a) A 69-year-old male patient diagnosed with Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) 2R2-B3 associated with multiple wedge fragments. (b) After open reduction and plate fixation, a cortical defect on the medial side was identified (black arrow). (c) A separate medial wedge fragment (white arrow) created a cortical defect and was at risk of devitalization if anatomical reduction had been attempted. (d) rhBMP-2 was applied to the medial cortical defect and along the fracture line between the stripped wedge fragment and the distal diaphysis (white arrow). (e) Postoperative radiograph showing fixation with a 3.5 mm locking plate and a 2.0 mm reduction plate. A hydroxyapatite (HA)-based carrier system containing 0.5 mg of rhBMP-2 is visible on the medial, lateral, and dorsal aspects of the ulnar fracture site. (f) Fracture healing was achieved without evidence of heterotopic ossification or radioulnar synostosis. The grafted material was resorbed during the fracture healing process. (g) The patient achieved a favorable functional outcome without any significant limitation in range of motion.

Figure 1

Surgical implementation of hydroxyapatite-carrier rhBMP-2. (a) A 69-year-old male patient diagnosed with Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) 2R2-B3 associated with multiple wedge fragments. (b) After open reduction and plate fixation, a cortical defect on the medial side was identified (black arrow). (c) A separate medial wedge fragment (white arrow) created a cortical defect and was at risk of devitalization if anatomical reduction had been attempted. (d) rhBMP-2 was applied to the medial cortical defect and along the fracture line between the stripped wedge fragment and the distal diaphysis (white arrow). (e) Postoperative radiograph showing fixation with a 3.5 mm locking plate and a 2.0 mm reduction plate. A hydroxyapatite (HA)-based carrier system containing 0.5 mg of rhBMP-2 is visible on the medial, lateral, and dorsal aspects of the ulnar fracture site. (f) Fracture healing was achieved without evidence of heterotopic ossification or radioulnar synostosis. The grafted material was resorbed during the fracture healing process. (g) The patient achieved a favorable functional outcome without any significant limitation in range of motion.

Figure 2

Flow chart of the study.