Comparative Efficacy of the Masquelet Versus Titanium Mesh Cage Techniques for the Treatment of Large Long Bone Defects

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.

Inclusion Criteria:

Presence of an extremity long bone (femur, tibia, humerus, ulna, radius) segmental defect
requiring surgical reconstruction with at least one of the following etiologies:

- traumatic segmental bone defect that warrants surgical reconstruction;

- acquired bony nonunion (not congenital) treatable by segmental resection and
reconstruction;

- local osteomyelitis (dormant or active) treatable by segmental bone resection and
reconstruction;

- localized, nonmalignant tumor with involvement of bone diaphysis treatable by
segmental bone resection and reconstruction.

Exclusion Criteria:

- Non-segmental defects (eg, defect in continuity involving only single cortex);

- Inability or contraindications to achieve stabilization with an intramedullary (IM)
nail;

- Insufficient defect size (humerus defects <5 cm; femur or tibia defect <2 cm in
length);

- Extremity unsuitable for salvage;

- Patients with inadequate neuro-vascular status;

- Defect and/or soft tissue status ineligible for surgical reconstruction;

- Ipsilateral extremity defect (eg, tibia and femur ipsilateral defects);

- Skeletal immaturity (open growth plate and/or age <18 years);

- Known allergic reaction to titanium implants;

- Disseminated osteomyelitis throughout the bone;

- Active systemic infection at time of surgery;

- Congenital / genetic etiology of nonunion (congenital pseudoarthrosis, osteogenesis
imperfecta, etc.);

- Women who are pregnant or nursing;

- Women who intend to become pregnant during the study followup (ie, 2 years);

- Disseminated and/or nonresectable malignant tumor involving bone;

- Patients with active compartment syndrome;

- Prisoners;

- Patients considered as non-compliant with medical and follow up care;

- Patients using narcotics, abusing prescription drugs (within last 2 years);

- Patients with alcohol abuse;

- Patients deemed incapable of following instructions pertaining to post operative care
due to mental or medical condition;

- Patients deemed ineligible due to medico-social concerns.