"NEW WAYS TO HEAL FRACTURES ENTER MARKET IN THE WORKS"

ORTHOPEDICS TODAY 16(l)

ARTICLE REVIEW

PAUL MCNALLY, D.O., Resident, Orthopaedic Surgery

FREEMAN MILLER, M.D. Attending Pediatric Orthopaedic Surgeon

CLINICAL CASE PRESENTATION

ORTHOPAEDIC DEPARTMENT

THE ALFRED I. DUPONT INSTITUTE

WILMINGTON, DELAWARE

GENERAL INFORMATION:

• 5.6 million fracture annually
• 5 to 10% have impaired or delayed healing

TWO WAYS OF AIDING HEALING:

1. Osteoconduction - product supports the ingrowth of capillaries, perivascular tissues, and osteoprogenitor cells from a host into an implant or graft
2. Osteoinduction - elicits mesenchymal stem cells from the surrounding area that differentiate into osteoblasts -ideal product: combination of osteoconductive material and osteoinductive agent

NEW BONE GRAFTS:

1. Pro Osteon -
• Interpore International
• Type: Bone graft substitute
• Composition: sea coral converted by hydrothermal exchange reaction into Coralline Hydroxyappatite
• Action: acts as lattice for new bone formation
• Indications (approved): metaphyseal
• fractures of long bones
• Trials: Being evaluated in cervical spine fusions
2. Bioglass US Biomaterials Corp,
• Type: Bioactive glass implant
• Action: reacts with body fluid causing bone-like pores to evolve on the implant surface, Collagen bonds to the surface and new bone forms and fills the space between the implant, collagen fibers and bone.
• Indications (approved): Only for grafting facial bones, replacing bones in the middle ear, and repairing periodontal defects
• Trials: long bone fracture fixation, spinal fusions, and joint repi.
3. Collagraft Zimmer
• Type: synthetic bone graft substitute
• Composition: Hydroxyapatite/tricalcium phosphate and pure bovine fibrillar collagen
• Action: Mix with autogenous bone marrow to produce an osteoconductive and osteoinductive substance that acts as a matrix for repair process
• Indications (approved): repair of
• diaphyseal/metaphyseal fxs
• note: fx should be stabilized with skeletal fixation and recommended maximum defect site of 30cc
• Risk: Immunologic risk secondary to bovine coliagen (no reported serious cases)
4. Grafton Osteotech
• Type: Banked human tissue
• Composition: Demineralized bone matrix glycerol suspension
• Action: elicits new bone formation by osteoconduction and osteoinduction.
• Indications (approved): as adjunctive to spinal and joint fusions, repair of osseous defects, and arthroplasties
• Risk: Possible disease transmission
• NOTE: processing of Grafton has been shown to inactivate HIV, Hepatitis B&C, cytomegalovirus, and Polio

EXPERIMENTAL PRODUCTS: (AWAITING FDA APPROVAL)

1. Norian Skeletal Repair System (SRS)
• Type: Bone mineral substitute
• Composition: Monocalcium and tricalcium phosphate, calcium carbonate and liquid sodium phosphate
• Action: Paste that hardens to turn into the mineral phase of bone (osteoconductive). Is replaced by bone, Maximum comp, strength greater than cancellous bone
2. Bone Source Hydroxyapatite Cement -(Developmental)
• Type: Hydroxyapatite bone Subst.
• Composition: Nonceramic Hydroxyapatite
• Action: Initially formed into a paste that hardens over 20-30 min. and converts to hydroxyapatite in 4hrs Eventually replaced by new bone.
3. Transforming Growth Factor-Beta One (TGF-Bl)
• Type: Osteoinductive Protein
• Action: awaiting FDA approval on its effects on bone tissue growth and regeneration
• Note: No humans studies yet
• Future Applications: nonunions, bone defects, and revision
• implant surgery
4. OP-1 - (currently in clinical trials)
• Type: morphogenic protein
• Action: stimulates bone formation by causing precursor stem cells to differentiate into bone-forming cells
5. BMP-2 - (human clinical trials)
• Type: Bone growth protein
• Action: induces bone growth & and repair when mixed with carrier and implanted into site of fracture
• Future applications: Trauma, AVN, Boneloss from tumor, and spinal reconstruction