Improved bone formation in smokers with recombinant human bone morphogenetic protein–2

Abstract

Harvinder S. Sandhu, MD, New York, NY, USA; Rick B. Delamarter, MD, Linda E.A. Kanim, MA, Santa Monica, CA, USA; Frank P. Cammisa, Jr., MD, New York, NY, USA; Aleksandar Curcin, MD, Baltimore, MD, USA; Edward N. Hanley, Jr., MD, Charlotte, NC, USA; Jeffrey S. Fischgrund, MD, Southfield, MI, USA; Alexandre Valentin-Opran, MD, Cambridge, MA, USA; Thomas Lang, MD, San Francisco, CA, USAIntroduction: Smoking clearly inhibits bone fusion in spinal surgery patients. Recombinant human bone morphogenetic protein (rhBMP)-2 has been shown to increase bone formation. Can rhBMP-2 reverse the deleterious effects of smoking?Purpose: To assess bone formation after implantation of varying concentrations of rhBMP-2 in attempted reconstruction of the iliac autogenous bone donor site in patients undergoing cervical fusion with and without a reported history of smoking.Methods: A four-center, patient-blinded, randomized controlled study comparing reconstruction of the iliac crest donor site with three doses of rhBMP-2/Absorbable Collagen Sponge (ACS) to buffer/ACS or standard methods of closure (iliac defect left empty) was conducted. Forty patients undergoing a one- or two-level cervical fusion procedure requiring autogenous iliac crest bone grafting were informed of the study, enrolled and randomized before surgery (between 1998 and 1999). The iliac crest harvest technique was standardized. Donor site was left empty (n=8), reconstructed with buffer/ACS (n=8) or with rhBMP-2/ACS 0.43 mg/ml (n=8), 0.75 mg/ml (n=8) or 1.50 mg/ml (n=8). At the time of enrollment, patients reported recent smoking history (ever and current smokers). Osteoinduction was monitored at baseline and 24 weeks on computed tomography (CT) and three-dimensional reconstructions. “Bridging bone” was considered as none (0), small to moderate (1) or extensive (2) filling in of the defect. Multivariate analysis techniques were used.Results: Follow-up evaluations were completed by all patients (CT available on 39 patients). Mean age was 42 years (range, 26 to 33 years); 65% of patients were men and 35% women. Thirteen patients reported a history of smoking, and 26 patients had no recent smoking history. Rates of smoking were comparable among all treatment groups. Bridging bone occurred more frequently in patients without a smoking history than for those with a history across all treatments except for 1.5 mg/ml rhBMP-2/ACS (highest dose). After 1.5 mg/dl rhBMP-2 administration, there was no difference in osteoinduction, bridging bone in the defect site, between patients with and without a history of smoking (overall model logistic, p<.05).Conclusion: Although bone formation was less for patients with a recent history of smoking at lower doses of rhBMP-2, these differences were not observed at the dose of 1.5 mg/ml rhBMP-2. Treatment with the highest concentration of rhBMP-2 may overcome the nicotine effect on osteoinduction. Despite these very early and preliminary results, smoking cessation before a fusion procedure is crucial.