Clinical Validation of Allogeneic Morphogenetic Protein: Donor Intervariability,
Terminal Irradiation and Age of Product is not Clinically Relevant
Christopher Yeung
1*
, Justin Field
1
and Jeffrey Roh
2
1
Desert Institute for Spine Care, Phoenix, AZ, USA
2
Orthopedics International, Kirkland, WA, USA
*
Corresponding author: Christopher Yeung, Desert Institute for Spine Care, 1635 E Myrtle Ave, Phoenix, AZ, USA, Tel: 602-944-2900; E-mail:
christopheryeungmd@gmail.com
Rec date: Jan 14, 2014, Acc date: Jun 26, 2014, Pub date: Jun 29, 2014
Copyright: © 2014 Yeung C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Donor to donor variation has long been a concern of the allograft industry. DBM and stem cell products have
been particularly susceptible to intervariability between donors, regardless of the process used to manufacture these
products. Manufacturers of allograft based products have often utilized in vitro or small animal models to help predict
reliability, yet little data is available correlating preclinical outcomes with clinical efficacy.
OsteoAMP is a commercially available allograft-derived growth factor rich in osteoinductive, angiogenic, and
mitogenic proteins. An analysis of radiographic results comparing fusion outcomes was conducted for 285
consecutive cervical and lumbar spinal fusion patients utilizing OsteoAMP bone grafts from 114 donors of varying
ages. A blinded radiological fusion assessment, performed by an independent radiologist, showed all patients,
except one, fused within 18 months (average time to fusion was 189.9 days). This evidentiary analysis shows that
OsteoAMP fusion success did not show donor intervariability and that fusion rate/time is not dependent on donor
age. In addition, the implant retained bioactivity over time and terminal sterilization via low-dose gamma irradiation
did not impair the bioactivity of the grafts.
Keywords: Donor intervariability; Allograft; OsteoAMP; Spine
fusion
Introduction
Clinical efficacy between donors has been a challenge in the
allograft industry for many decades [1,2]. Compounding the problem,
research has shown that there is in fact more variability between
donors than between products and the processes used to manufacture
these products [3,4]. Variables contributing to these concerns include
donor age and gender, processing techniques and sterilization
methods [2,5]. According to the U.S. Department of Health & Human
Services approximately 60% of deceased donors recovered in the US
between 1988 and 2013 were male with the majority of all donors
ranging in age between 35 and 64 years.
To try and predict efficacy of the tissue recovered, demineralized
bone matrix (DBM) products and stem cell products often utilize in
vitro or ectopic rat in vivo assays. There have been little data
correlating preclinical outcomes with clinical efficacy, limiting the
value of such testing [2]. Quite often, the donor material tested
preclinically is at an intermediary processing step, prior to terminal
sterilization and storage.
Sterilization is a critical process to ensure graft preservation [6].
There have been a number of product recalls in recent years for
products that do not undergo terminal sterilization. In particular,
allograft-derived stem cell products have been reported to the US Food
and Drug Administration for contamination of hepatitis [7] and
multiple strains of clostridium [8-10]. Terminal sterilization provides
the surgeon with an additional safeguard against microbial
contaminates, although the perceived detrimental effects of irradiation
have caused uncertainty in its overall clinical value [11]. Studies have
shown that irradiation with 25 kGy reduces osteoblast differentiation
and expression of BMP-7 when compared to non-irradiated human
bone allograft implanted in a nude rat model [12]. Other studies have
shown that irradiation used by bone banks did not influence the
inductive properties of DBM [13,14]. In addition, adding a carrier like
lecithin to a DBM could negatively influence biological activity after
sterilization [11]. This study attempted to identify the effects of
processing and donor selection used for a novel allograft growth factor
by analyzing the fusion rates of patients that underwent spine surgery.
It was hypothesized that the growth factors remained bioavailable and
were not affected by the age of the donor, the age of the product or
whether the product was irradiated.
Methods and Materials
A retrospective radiographic analysis was conducted to evaluate the
fusion success rate in patients receiving allograft material from donors
of different genders, ages and preparations utilizing a commercially
available allogeneic morphogenetic protein, OsteoAMP® (Advanced
Biologics, Carlsbad, CA). The study involved two sites with three
treating physicians total. The indications for surgery were
symptomatic patients diagnosed with degenerative disc disease
(DDD), stenosis, and/or spondylolisthesis.
OsteoAMP bone allograft was processed from human cadavers
cleared for implantation utilizing a proprietary processing technique.
OsteoAMP was selected as the biologic and used in conjunction with
the centers’ preferred spinal spacer and fixation system. All products
were prepared per the instructions for use. No other biologic product
Spine
Yeung, et al., J Spine 2014, 3:3
http://dx.doi.org/10.4172/2165-7939.1000173
Research Article Open Access
J Spine
ISSN:2165-7939 JSP, an open access journal
Volume 3 • Issue 3 • 1000173