Comparative Efficacy of the Masquelet Versus Titanium Mesh Cage Techniques for the Treatment of Large Long Bone Defects
Condition: Segmental Long Bone Defects
Study type: Interventional

Summary: 
      The United States Department of Defense (DoD) is funding exciting new research at the
      University of Texas Medical Branch (UTMB) Department of Orthopaedic Surgery and
      Rehabilitation that can be a major improvement in the treatment of extremity trauma involving
      segmental bone loss. These devastating injuries occur frequently in both civilians and the
      military. They typically result from motor vehicle accidents, high-energy fractures, gunshot
      injuries, and blast injuries, but also from the surgical removal of a bone segment because of
      infection or tumor. Despite many modern medical advances in this area, bone healing that can
      adequately replace bone loss and restore pre-injury limb function is extremely difficult to
      achieve. Existing standard treatment procedures are exceedingly complicated, require highly
      specialized equipment and clinical skills, and usually require many surgical procedures over
      many months or years. Despite these effort and costs, major complications usually occur with
      all the standard treatment options, the patient's ability to return to an acceptable
      functional status is typically low, and, therefore, many of these patients have their limbs
      amputated.

      The UTMB Department of Orthopaedic Surgery and Rehabilitation will conduct a DoD-funded
      clinical trial to determine and compare the advantages of two new and innovative surgical
      bone defect treatment techniques that can be significantly more effective for wounded
      warriors or civilian patients and with these conditions. One treatment method, called "the
      Masquelet Technique", involves two-stage surgery: the first one to create a biomembrane
      around the defect by applying a cement spacer, and then the second one for cement spacer
      removal and defect bone grafting. The other method, developed by UTMB physicians, is "the
      Cage Technique" and it comprises one-stage surgery in which a special hollow, fenestrated,
      titanium cage filled with bone graft is implanted in the defect. Initial clinical experience
      with both of these techniques has been very promising, but to date, there has been no
      prospective clinical study comparing the two new methods of defect treatment. Identifying an
      optimal surgical bone defect reconstructive technique would significantly improve the
      clinical outcomes of patients with these challenging conditions.
    

Detailed description: 
      Background: Segmental long bone defects remain a formidable treatment challenge. All the
      existing standard treatment options have major limitations and often culminate in limb
      amputation or permanent functional deficits. We developed a novel, one-stage alternative
      treatment for segmental bone loss that utilizes the cylindrical titanium mesh cage (CTMC) in
      combination with bone graft, and have established its clinical merits in an initial clinical
      series. Shortly thereafter, Masquelet reported another new defect reconstruction technique
      that involves two-stage approach: first inducing biomembrane formation with a cement spacer,
      and subsequent spacer removal and bone grafting. Both the Masquelet and the CTMC techniques
      are based on the principle of graft containment to render optimal potential for graft to heal
      the defect; however, they differ in primary biological versus biomechanical functions
      provided by the containment. The Masquelet biomembrane containment, being a rich source of
      vascular supply and growth factors, creates an excellent biological milieu for graft, but
      requires an additional surgery and is associated with prolonged protected weight bearing
      until graft consolidation occurs. Conversely, the benefit of the CTMC technique is primarily
      the biomechanical support it provides for graft and the reconstructed extremity, thereby
      permitting immediate functional restoration without mobility or weight bearing restrictions
      during the bone healing process. Although both Masquelet and the CTMC techniques have been
      effective in the treatment of large segmental bone defects, there is no prospective,
      well-controlled study comparing their therapeutic efficacies for specific clinical
      indications.

      Objective: Determining the clinical efficacy and cost-effectiveness of the Masquelet (Arm I)
      versus the CTMC technique (Arm II) in combination with reamer-irrigator-aspirator (RIA)
      harvested autograft (Option A) or allograft-demineralized bone matrix (DBM) composite (Option
      II) in the treatment of segmental long bone deficiencies.

      Specific Aims: 1) Establish the effects of the specific patient and bone defect
      characteristics on the treatment outcome; 2) Determine and compare clinical efficacies of the
      reconstruction techniques (Arm I vs Arm II); 3) Establish the merits of using specific graft
      type (Option A vs Option B) within and across each study arms; 3) Develop a quantitative
      predictive model to improve clinical decision making, and 4) Assess and compare the
      cost-effectiveness and resource expenditures incurred by the specific treatment selection.

      Study Design: Single-center, multi-site, two-arm, randomized clinical trial. Thirty patients
      with segmental bone deficiency as a result of trauma, gunshot, iatrogenic resection due to
      infection, nonunion, or neoplasm will be enrolled and randomized to receive either the
      Masquelet (Arm I) or the CTMC as definitive defect treatment (Arm II). Bone graft selection
      will include either RIA-harvested autograft (Option A) or allograft croutons-DBM composite
      (Option B). Patients will be followed up to18 months. The data collected will include routine
      patient baseline information, systemic and extremity injury characteristics, bone defect
      characteristics, pre- and post-operative clinical examinations and imaging, validated
      functional outcomes measures, and associated cost expenditure. Descriptive statistics will be
      used to analyze and compare the results specifically related to the rate of defect healing
      and functional recovery. Paired t-test will be used to test the effects of the defect
      reconstruction option on the outcome measures. Analysis of covariance will be used for
      pair-wise comparison between the arms and within/across each bone graft option. Multiple
      models will be used to produce an accurate predictive model which accounts for possible
      morbidities and interactions. Derived from the joint distribution of costs and effects,
      cost-effectiveness acceptability curves will be established and compared for the study arms.

      Military Relevance: Many combat injuries involve extremity trauma with segmental bone loss,
      and the extent to which they can be successfully treated impacts the function and quality of
      life of the wounded warrior. The Masquelet and the CTMC been developed as innovative,
      biologically-sound defect reconstructive techniques to address the complexity of therapeutic
      concerns associated with these conditions (ie, immediate restoration of limb
      alignment/stability, early motion, weight bearing). The proposed trial aims to compare the
      efficacy of these techniques to identify the one that can be instantly adopted and applied by
      military surgeons.
    

Intervention name(s): Autogenous RIA bone grafting; Allogeneic bone grafting
Intervention type(s): Procedure; Procedure
Intervention description(s): After aseptic defect and adequate soft tissue coverage have been achieved, the defect reconstruction technique will include autogenous bone grafting harvesting using Reamer-Irrigator-Aspirator (RIA) and packing it within the defect.; After aseptic defect and adequate soft tissue coverage have been achieved, the defect reconstruction technique will include defect packing with allogeneic bone graft croutons combined with demineralized bone matrix (DBM).
Other intervention name(s): RIA grafting; Allograft
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: bone defects; iatrogenic resection; titanium mesh cage; biomembrane; Masquelet technique