Session XI - Tibia

Sat., 10/7/06 Tibia, Paper #62, 11:09 am

Safety and Efficacy Evaluation of Injectable rhBMP-2 in Patients with Closed Tibia Fractures

Amratlal D. Patel, FRCS1 (a); Simon Donell, MD1 (a); Thomas Lyon, MD2 (a); Lisa K. Cannada, MD3 (a); Steven J. Morgan, MD4 (a); Wim H. Scheele, MD5 (e); Alexandre Valentin-Opran, MD5 (a);
1Norfolk & Norwich University Hospital Department of Orthopaedics, Norwich, United Kingdom;
2Lutheran Medical Center Department of Trauma Services, Wheat Ridge, Colorado, USA;
3University of Texas Southwestern Medical Center, Dallas, Texas, USA;
4Department of Orthopaedics Denver Health Medical Center, Denver, Colorado, USA;
5Wyeth Research, Cambridge, Massachusetts, USA

Purpose: This study evaluated percutaneous injections of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a specially formulated calcium phosphate matrix (CPM) and its effect on the time to union in OTA class 42 A or B closed tibia fractures.

Methods: This multicenter, prospective, dose-escalating evaluation assessed 41 patients, mean age 35 (range, 19-58). All patients were treated with a reamed, locked intramedullary (IM) nail, within 24 hours of injury. Five ml of paste were injected percutaneously under fluoroscopic control, along the lateral and posterior borders of the tibia at the fracture line. According to their treatment group, patients received one of 2 doses of rhBMP-2/CPM, injected either at the time of fracture fixation (Groups 1 and 2) or 7-9 days later (Groups 3 and 4). Radiographic and clinical fracture healing, adverse events, and antibodies to BMP-2 were assessed at 10 follow-up evaluations, scheduled over 52 weeks. The main study outcomes were time to radiographic and clinical fracture healing and the evaluation of adverse events related to the application of material. Results were compared to data from 40 patients treated at 2 of the 7 participating centers but not part of the original study, matched for fracture severity, fixation, and timing of radiographs.

Results: One transient, sterile drainage at the fracture site, one superficial infection, and failed locking screws in 2 patients were reported and resolved without surgical reintervention. Two patients developed antiBMP-2 antibodies. All patients healed. The mean time to union was 8.4 to 11.5 weeks, with no difference noted in time to healing between the 2 doses but a positive trend suggesting that delayed injections resulted in faster healing rates than acute. Compared to our historical controls, the mean time to radiographic healing was reduced by 3 to 6 weeks (20% to 42% reduction).
 Control  Group 1  Group 2  Group 3  Group 4
 N = 40  N = 11  N = 12  N = 9  N = 9
 rhBMP-2 dose (mgs)  N/A  5  10  5  10
 Days to rhBMP-2 injection  N/A  2  2  7­9  7­9
 Weeks (±SD) to radiographic healing  14.5 (7.8)  11.2 (2.3)  11.5 (7.3)  8.4 (3.0)  10.2 (4.2)

Conclusion/Significance: This first clinical evaluation of the percutaneous administration of rhBMP-2/CPM suggests the new administration method is feasible and generally well tolerated. The positive trend observed in this study vs. historical controls justifies further controlled evaluation of rhBMP-2 for the most appropriate time of administration and efficacy in patients with closed diaphyseal tibia fractures, to accelerate fracture healing and the return to normal function.

If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
· The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an "off label" use). · · FDA information not available at time of printing.