Dangers of bone graft substitutes: lessons from using GeneX

Area of Science:

• Orthopedic Surgery
• Biomaterials Science
• Regenerative Medicine

Background:

• Bone graft substitutes are crucial in spinal surgery.
• GeneX, a bone graft substitute composed of tri-calcium phosphate and calcium sulphate, is investigated for complications.
• Current regulatory pathways for bone graft substitutes are examined.

Observation:

• Three patients receiving GeneX for spinal fusion experienced severe adverse events, including sterile pus, skin breakdown, and pharyngeal perforation.
• Animal studies demonstrated GeneX induced significant tissue damage and inflammation compared to de-mineralized bone matrix (DBX) or saline.
• Regulatory bodies like the FDA and MHRA classify bone graft substitutes as medical devices, bypassing pre-market clinical safety trials required for drugs.

Findings:

• GeneX is associated with significant soft tissue inflammation and destructive potential.
• The material demonstrated a higher inflammatory response and tissue damage in mice compared to controls.
• The regulatory classification of bone graft substitutes as medical devices permits market entry without rigorous pre-clinical safety validation.

Implications:

• GeneX should be used with extreme caution, avoiding placement adjacent to delicate structures like the skin or pharynx due to erosion risk.
• Mandatory, comprehensive safety testing for bone graft substitutes is essential prior to their approval and clinical application.
• Reclassifying bone graft substitutes as drugs could ensure adequate safety evaluations, protecting patient well-being.