2007 Award Winners

Poster #12
John H. Moe Award Nominee

Aprotinin Inhibits Bone Formation In Vitro

Jonathan G. Schoenecker, MD; Mr. Nicholas Mignemi; Heidi Hamm, PhD; Herbert Schwartz, MD; Ginger Holt, MD; Gregory Mencio, MD

Introduction: Aprotinin is an antifibrinolytic that is used in surgery to reduce blood loss and decrease blood transfusion. Level one evidence supports its use in adult and pediatric spine surgery. The purpose of this study was to determine if aprotinin alters bone growth in vitro.

Methods: Immortalized osteoblast progenitor cells (MC3T3-E1) were cultured in differentiation buffer with logarithmic doses of aprotinin. Determination of bone formation and osteoblast differentiation were measured by quantification of matrix calcification, genomic analysis of osteoblast differentiation markers and measurement of alkaline phosphatase levels.

Results: Aprotinin dose dependently inhibited osteoblast differentiation and matrix calcification. Despite retaining their viability, osteoblasts treated at therapeutic doses of aprotinin (50-500KIU/ml) expressed only basal levels of alkaline phosphatase, and did not express significant levels of osteoblast differentiation markers CBFA, osteocalcin or procollagen-1. Further, osteoblasts cultured in therapeutic concentrations of aprotinin did not form mineralized matrix as measured by Von Kossa staining. Cells cultured with 50 KIU/ml aprotinin were able to recover their ability to differentiate and form mineralized matrix after aprotinin was removed.

Conclusion: Therapeutic concentrations of aprotinin inhibit bone formation in cell culture. This would suggest that the use of aprotinin could influence rates of spinal fusion. Although the mechanism of inhibition is not clear, it likely involves the inhibition of the serine proteases such as plasmin, uPA and tPA, all of which are produced by osteoblasts and are thought to be important in bone formation.

Bone Nodule Formation In Vitro

Osteoblasts cultured with logarithmic doses of aprotinin stained by VonKossa to show matrix mineralization. The therapeutic dose of aprotinin is 50-500 KIU/ml

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