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Osseointegration

What is Osseointegration?

Osseointegration is defined as: “Direct anchorage of an implant by formation of bony tissue around the implant, without the growth of fibrous tissue at the bone-implant interface.” (Dorland 1994). The pioneering work on osseointegration of titanium implants in craniomaxillofacial reconstruction was made by Professor P-I Brånemark in Gothenburg (Brånemark 1977). In oral surgery the concept of direct skeletal anchorage of titanium implants is considered as state of the art therapy for edentulism (Adell 1990).

The technique termed Osseointegration developed by Professor Per Ingvar Brånemark in the mid 1960’s had become firmly established in the field of dental implant technology. Professor Rickard Brånemark (Per Ingvar’s son) later applied this technique to long bones in 1990 when he introduced a pure titanium fixture into the femur of a transfemoral amputee in the first stage (Stage 1) of a two stage surgical procedure. The second stage surgery (Stage 2) entailed the refashioning of the soft tissue and introduction of a titanium abutment into the internal fixture secured under tension with a titanium alloy screw. This device, now known as the Osseointegrated Prosthesis for the Rehabilitation of Amputees (OPRA) Implant, the titanium abutment protrudes through the skin as the point of attachment for the external prosthesis.

Osseointegrated Prosthesis for the Rehabilitation of Amputees (OPRA) system

Who is Osseointegration Suitable for?
Osseointegration has the potential to improve function and quality of life of patients with amputations due to cancer, traumatic accidents and, as is the case of many of our patients, debilitating combat injuries. Osseointegration has the potential to provide greater range of motion, greater stability, improved osseoproprioception and reduced soft tissue irritation due to socket incompatibility. Osseointegration surgery for amputees is ideal at this stage in the field development only for the subset of patients who cannot tolerate regular wear of traditional, socket-based prostheses. Only patients that have documented difficulty with prosthetic wear due to conditions including ulceration(s), socket discomfort, excessive perspiration, intolerance to interface materials, or other inadequate methods of suspension should currently seek osseointegration surgery. Patients with osteoporosis, insulin dependent diabetes mellitus or are currently undergoing chemotherapy treatments are also not good candidates for the procedure. Within the United States, only transhumeral (above elbow), transfemoral (above knee) amputees are eligible for the procedure using the OPRA implant or one of the current clinical trials using one of the other investigational devices. Transtibial (below knee), transradial (below elbow) or thumb or digit amputees are not being considered at this stage.

Program Overview and Background
The DoD Osseointegration Program was initiated in 2015 and with the input of military, academic and industry expert’s participation and advice has sought to advance the field of osseointegration within the United States and bring osseointegration as a capability within the Military Health System. The DoD Osseointegration Program transitioned from translational research into the clinic in 2016 with Uniformed Services University serving as the coordinating center for the clinical program. This program will conduct and advance novel strategies to benefit active duty and retired amputees. Previously, we had developed a porcine model to optimize the skin-implant interface, and to support preclinical studies as part of an FDA Investigational Device Exemption. The DoD Osseointegration Program is currently conducting a clinical safety trial called the Transhumeral Amputee Osseointegration Study (TAOS) with the OPRA device for transhumeral patients. Walter Reed National Military Medical Center is the lead surgical institution to examine and advance osseointegration capabilities into the Military Health System to benefit our combat veterans and other beneficiaries. The DoD Osseointegration team has been working with the University of California San Francisco in preparation of expanding the TAOS program and to conduct future work examining the benefits for transfemoral patients for the FDA approved OPRA device for lower extremity patients. The Transfemoral Amputee Osseointegration Study (TFAOS) using the OPRA implant will commence in late 2017. Additional clinical trials and FDA approvals for other implant systems and additional indications will be coming soon. Future research and development continues with existing DoD efforts such as the DARPA Revolutionizing Prosthetics and HAPTIX programs, targeted muscle reinnervation (TMR), and implantable myoelectric sensors (IMES) for terminal device control. Furthermore, this technology permits the evaluation and validation of advanced prosthetic components (e.g., microprocessor or powered components) while avoiding confounding socket-related issues. Ultimately osseointegration aims to provide improved functional independence and improved quality of life for the unique patient population.

Osseointegration has the potential of bringing improved functionality and quality of life to patients with amputations due to cancer, traumatic accident and in the case of our patients debilitating combat injuries. Many combat and blast-related amputees have difficulty with prosthesis wear. This affects functional mobility and often means the difference between wheelchair dependence and independent ambulation. Difficulties are due, in large part, to the manner in which current prostheses attach to the body. Modern prostheses require a socket that transfers the force generated by a patient's environment (e.g. by the ground when walking) to the patient's skin, subcutaneous soft-tissues, and muscle envelope before being transferred to the appendicular skeleton. The high rate of complications observed in our combat-wounded population adds to the problem. Heterotopic ossification (HO), which occurs in greater than 60% of combat amputees, is shown in and known to decrease tissue compliance, cause ulcerations and local pain, and increase the number of symptomatic neuromas. In addition, split thickness skin grafts are used to preserve residual limb length, but are less durable and prone to ulceration under traditional sockets. All of these issues can make it more difficult for a combat or blast-related amputee to successfully don and tolerate a functional prosthesis. With the use of an osseointegrated prosthetic, combat wounded service personnel are able to gain greater independence and improve quality of life post recovery.

The TAOS project received four years of research funding from the Defense Health Program in coordination with JPC-8 from the US Army Medical Research and Material Command to begin conducting a FDA-regulated clinical trial to evaluate the OPRA device in patients with transhumeral amputations in the near-term. The first three patients enrolled in the study at Walter Reed National Military Medical Center and the first successful Stage 1 surgeries were conducted in October 2016 where the titanium bone fixture was implanted. Stage 2 surgeries to attach the transdermal abutment that will eventually attach to the external prosthesis were performed in early 2017 once full osseointegration of the fixture had occurred.

The surgical implantation of osseointegrated devices such as the OPRA device is only one component of the effort. Our commitment to a comprehensive evaluation of Osseointegration includes developing rehabilitation paradigms and developing repeatable surgical techniques that can become the standard of care for osseointegration patients. CDR Forsberg and LTC Potter have participated in surgeries for all Osseointegration implants available worldwide in an effort to bring The DoD Osseointegration Program has partnered with the Rehabilitation Department at USUHS and the Extremity Trauma and Amputation Center of Excellence (EACE) to hire a fulltime Occupational Therapist, and a Prosthetics Technician so that the DoD Osseointegration Program has the capacity and expertise to have a complete multi-dimensional team to serve the complete needs of the combat wounded amputee.

Finally, the DoD Osseointegration Program has been laying the ground work for a larger integrated effort to understand and incorporate complimentary research technology the DoD is evaluating that will provide for continual improvement of osseointegrated technologies going forward. This collaborative effort includes work with University of California San Francisco, University of Michigan, Massachusetts Institute of Technology, SUNY Buffalo, University of Pittsburg, University of Rochester, Johns Hopkins APL, Wake Forest Institute of Regenerative Medicine, University of Minnesota, DARPA, Office of Naval Research and the Royal Airforce in the United Kingdom.

DoD Osseointegration Program Steering Committee Members

CDR Jonathan A. Forsberg
, MD, PhD, Orthopaedic Oncologist, USU-WR Dept. Surgery
LTC Benjamin Kyle Potter, MD, FACS, Chief, Orthopaedic Surgery, WRNMMC
Captain Eric Elster, MD FACS, Professor and Chairman, Department of Surgery at USUHS.
COL (ret.) Paul Pasquina, MD, Chief, Dept. of Orthopaedics and Rehabilitation, WRNMMC
M. Dave Beachler, Lead Prosthetist, Walter Reed National Military Medical Center
Gp Capt Jonathan Kendrew, MBBS, MRCS(Eng), FRCS (Tr&Orth), Royal Airforce, UK

Anthony Atala, MD, Director and Chair, Wake Forest Institute for Regenerative Medicine
Joan E. Bechtold, PhD, Dept. of Orthopedic Surgery /Biomedical Engineering, U of Minnesota
Kent Bachus, PhD, Research Professor, Orthopaedics, University of Utah
Rickard Brånemark, MD, MS, PhD, Professor, Department of Orthopaedic Surgery, UCSF
Mark Ehrensberger, PhD, Professor, Dept. of Biomedical Engineering, SUNY at Buffalo
Hugh Herr, PhD, Associate Professor, Biomechatronics Group, MIT
Todd A Kuiken, MD, PhD, Director, Center for Bionic Medicine, Shirley Ryan Ability Lab, Chicago
Richard L. McGough, III, MD, Chief, Division of Musculoskeletal Oncology, U Pittsburg
Richard J. O'Donnell, MD, Professor of Clinical Orthopaedic Surgery UCSF
Michelle Zawadski, Senior Director, Zimmer Biomet
R. Lor Randall, MD, FACS, Professor of Orthopaedics, University of Utah
John Shero, MHA, Director, DoD-VA Extremity Trauma & Amputation Center of Excellence.