73. Sex-based difference in response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral fusion model

Abstract

BACKGROUND CONTEXT Despite the known influence of hormones on bone metabolism and osteogenic differentiation, the few clinical studies evaluating outcomes after spine surgery have come to contradictory conclusions as to a sex-based differential response. This study aimed to quantify and compare the bone regenerative response to rhBMP-2 in males vs females in a preclinical setting of spine fusion. PURPOSE The purpose of this study was to determine whether sex influences fusion success, bone regenerative capacity, and bone quality after rhBMP-2-mediated spine fusion. STUDY DESIGN/SETTING Preclinical animal study. PATIENT SAMPLE Male and female Sprague-Dawley rats, ages 12-16 weeks. OUTCOME MEASURES Radiography, fusion scoring, microCT imaging, biomechanics testing. METHODS Twenty-four male and 24 female Sprague Dawley rats underwent L4-L5 posterolateral spine fusion with bilateral placement of an absorbable collagen sponge loaded with 5 μg of rhBMP-2 each (Infuse™; 10 μg/animal). Fusion was evaluated at 8 weeks postoperatively via blinded manual palpation on 14 rats/treatment group using an established scoring system wherein 0=no fusion, 1=unilateral fusion, 2=bilateral fusion, 3=bilateral fusion adjacent to a unilateral fusion, and 4=two adjacent bilateral fusion. A fusion score of 1 or greater (unilateral, single level fusion) was considered successfully fused. Specimens then underwent microCT imaging to evaluate and quantify new bone formation. Biomechanical testing was performed on the remaining 10 rats/group to quantify segmental flexion-extension range of motion and stiffness. RESULTS Both male and female rats achieved 100% fusion rates (with 1-level unilateral bridging considered fused), as assessed by blinded manual palpation. However, fusion scores were greater in male rats when compared with females (female: 2.4 vs males 3.1; p CONCLUSIONS Although a smaller amount of new bone was formed in females treated with Infuse™ relative to their male counterparts, that new bone was denser, with twice the number of trabeculae. Interestingly, female spines exhibited on average a greater segmental flexion-extension range-of-motion, suggesting that biomechanical stabilization may be more dependent upon fusion mass volume than density of the newly formed bone. These results are strongly suggestive of sex-dependent differences in the bone regenerative response to rhBMP-2, and they underscore the need for further study of this phenomenon and the underlying mechanisms involved. FDA DEVICE/DRUG STATUS rhBMP-2: Investigational.