Trevor P Scott MD

UCLA Orthopedic Surgery Resident

Dr. Farad Parhami PhDDr. Jeff Wang MDDr. Michael Daubs MDDr. Scott Montgomery MDDr. Akinobu Suzuki MDDr. Haijun Tian MDDr. Jared Johnson MDMr. Kevin Phan BSDr. Elisa Atta PhDDr. Sotirios Tetratis MDDr. Renata Pereira MD

A Comparison of a Novel Oxysterol Molecule to rhBMP2 in a Rabbit Posterolateral Fusion ModelTrevor Scott MD

My disclosure is in the Final Program and in the AAOS Orthopaedic Disclosure program.

Dr. Parhami discloses that he is a founder of MAX BioPharma Inc., which has licensed the rights to Oxy133

from UCLA, and that he has financial interests in the technology presented here. In addition, as part of the

licensing agreement, UCLA holds equity in MAX BioPharma. All other authors state that they have no

conflicts of interest.

Background Pseudarthrosis is a potential complication of major

spinal surgery and fracture surgeries

Iliac crest autografts, which remain the standard of care, have substantial donor site morbidity and may not provide enough graft volume for large surgeries

Biologics are an active area of research to find the best possible alternative to iliac crest autograft

Background rhBMP2 was approved in

2002 for single level lumbar fusion and its use spread rapidly

Recently concerns about possible complications of rhBMP2 have increased

Background Our lab has previously synthesized a compound,

oxysterol 133 (Oxy133), which showed promise as a biological adjunct to fusion

Equivalent to rhBMP2 in rat posterolateral fusion model

In vitro promotes significant osteogenic marker expression including Runx2, osterix, alkaline phosphatase, bone sialoprotein and osteocalcin

Purpose To compare the efficacy of rhBMP2 and oxysterol 133 in

a rabbit posterolateral lumbar fusion model

Methods In vitro study

24 rabbits underwent bilateral posterolateral lumbar fusion at L4-5

Groups: control (A), 30 ug rhBMP2 (B), 20 mg oxysterol 133 (C), 60 mg oxysterol 133 (D)

Fusion evaluated by fluorscopy at 4 weeks and by faxitron radiograph, microCT and manual palpation after sacrifice at 8 week

Figure 1

0% 50% 100% 150%

*

* Indicates p < 0.05 compared to group A (Control)

% Fusion

*

**

**

Control

30 mg BMP2

20 mg Oxy133

60 mg Oxy133

Figure 2

Control 30 µg BMP2 20 mg Oxy133 60 mg Oxy133Control 30 µg BMP2Control 30 µg BMP2Control 20 mg Oxy13330 µg BMP2Control 60 mg Oxy13320 mg Oxy13330 µg BMP2ControlControl 30 µg BMP2Control 20 mg Oxy13330 µg BMP2Control 60 mg Oxy13320 mg Oxy13330 µg BMP2Control

Fusion by Manual Palpation at 8 weeks

0% 20% 40% 60% 80% 100%

A

B

C

D

Fusion Rate*

* Indicates p < 0.05 compared to group A

% Fusion

*

*

Fusion Assessment by microCT

0% 20% 40% 60% 80% 100%

A

B

C

D

CT Lumbar SpinalFusion

* Indicates p < 0.05 compared to group A

% Fusion

*

*

*

Figure 5

60 mg Oxy13320 mg Oxy13330 µg BMP2Control

Fusion Rate Summary

Fusion Mass TV on microCT

0 500 1000 1500 2000 2500

Control

BMP2

Oxy 20

Oxy 60

Tissue Volume (mm^3)

Tissue Volume(mm^3)

*

*

*

* Indicates p<0.5 compared to control

Figure 6

60 mg Oxy13320 mg Oxy13330 µg BMP2Control

Conclusions High dose and lose dose oxysterol 133 show equivalent

fusion to rhBMP2,

Given its osteogenic potency, anticipated lack of immunogenicity, and low cost of production, Oxy133 may be an excellent alternative to rhBMP2 for spinal fusion procedures and is worthy of further study

Thank You

Dr. Farad Parhami PhD Dr. Jeff Wang MD Dr. Michael Daubs MD Dr. Scott Montgomery MD Dr. Akinobu Suzuki MD Dr. Haijun Tian MD Dr. Jared Johnson MD Kevin Phan BS Dr. Elisa Atta PhD Dr. Sotirios Tetratis MD Dr. Renata Pereira MD

Special thanks to:Allison Roe BSTaylor Hobson BS

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