Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair-A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Part 2-A Pilot Study of Functional Recovery and Structural Outcomes

Junji Ide, Yu Mochizuki, Arthur van Noort, Hiroshi Ochi, Sudhakar Sridharan, Eiji Itoi, Stefan Greiner, Junji Ide, Yu Mochizuki, Arthur van Noort, Hiroshi Ochi, Sudhakar Sridharan, Eiji Itoi, Stefan Greiner

Abstract

Background: The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site.

Purpose: To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein-12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up.

Study design: Randomized controlled trial; Level of evidence, 2.

Methods: A total of 20 patients were randomized into 2 groups, rhBMP-12/ACS and standard-of-care (SOC) control, with 16 and 4 patients, respectively. The patients underwent open repair of a rotator cuff tear at least 2 to 4 cm wide; in the rhBMP-12/ACS group, this was augmented with a bioscaffold containing rhBMP-12. Follow-up assessments were conducted with a 100-mm visual analog scale (VAS) for pain and active and passive ranges of motion (ROMs) including forward flexion, elevation in the scapular plane, abduction, and external rotation at 12, 16, 26, 39, and 52 weeks after surgery; isometric strength in scapular abduction and external rotation at 16, 26, 39, and 52 weeks; and magnetic resonance imaging (MRI) at 12 and 52 weeks.

Results: The mean VAS score decreased from 37.9 mm preoperatively to 13.8 mm at week 52, and ROM and isometric strength recovered at week 52 in the rhBMP-12/ACS group. The mean VAS score decreased from 48.3 mm preoperatively to 1.5 mm at week 52, and ROM (excluding external rotation) and isometric strength recovered by week 52 in the SOC control group. Of the 16 patients in the rhBMP-12/ACS group, 14 showed an intact repair at week 12; the MRI scans of the other 2 patients could not be evaluated because of artifacts. In the SOC control group, 1 patient showed repair failure. At week 52, 14 repairs in the rhBMP-12/ACS group and 2 repairs with available MRI scans in the SOC control group remained intact.

Conclusion: Functional recovery and structural outcomes in patients in whom rhBMP-12/ACS was used as adjuvant therapy in rotator cuff repair justify conducting future, larger, multicenter, prospective studies.

Registration: NCT00936559, NCT01122498 (ClinicalTrials.gov identifier).

Keywords: biological augmentation; growth factor; rhBMP-12; rotator cuff repair; tendon-to-bone healing.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by Pfizer Inc. H.O. and S.S. are employed by Pfizer.

Figures

Figure 1.
Figure 1.
CONSORT diagram of patient assignment. ACS, absorbable collagen sponge; rhBMP-12, recombinant human bone morphogenetic protein–12; SOC, standard of care.
Figure 2.
Figure 2.
Serial visual analog scale scores for pain in the rhBMP-12/ACS (solid line) and SOC control (broken line) groups. Values are presented as mean ± SD. ACS, absorbable collagen sponge; rhBMP-12, recombinant human bone morphogenetic protein–12; SOC, standard of care.
Figure 3.
Figure 3.
Serial active range of motion (ROM) measurements: (A) forward flexion, (B) elevation in the scapular plane, (C) abduction, and (D) external rotation. Solid line, rhBMP-12/ACS group; broken line, SOC control group. Values are presented as mean ± SD. ACS, absorbable collagen sponge; rhBMP-12, recombinant human bone morphogenetic protein–12; SOC, standard of care.
Figure 4.
Figure 4.
Serial isometric strength measurements: (A) scapular abduction and (B) external rotation. Solid line, rhBMP-12/ACS group; broken line, SOC control group. Values are presented as mean ± SD. ACS, absorbable collagen sponge; rhBMP-12, recombinant human bone morphogenetic protein–12; SOC, standard of care.
Figure 5.
Figure 5.
Postoperative magnetic resonance imaging (MRI) of (A) Sugaya type I: sufficient thickness with homogenously low intensity, (B) Sugaya type II: sufficient thickness with partial high intensity, (C) Sugaya type III: insufficient thickness without discontinuity, and (D) Sugaya type V: presence of major discontinuity.

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