Treat Implant Loosening of Percutaneous Osseointegrated Prosthetic Limbs with Intermittent Parathyroid Hormone
Abstract
The proposed work will address Osseointegration, a FY20 PRORP ARA Focus Area. We will evaluate an FDA-approved agent as a candidate to prevent and reverse the failure of percutaneous osseointegrated prosthetic limbs caused by implant loosening due to initial instability. Successful completion of this project will lead to a clinical trial on using this agent as a therapy for fibrotic osseointegration failure to benefit Veterans and civilians. Critical Problem: There are over 2.1 million people, including thousands of military personnel, in the United States living with limb loss. Over the last two decades, percutaneous osseointegrated (bone-anchored) prosthetic limbs have become more popular over conventional sockets. The success of bone-anchored prosthesis depends on rapid bone growth to attach the implant to the original bone. When implants fail to achieve initial fixation by bone, excessive fibrotic (scar) tissue forms at the bone-implant interface. This “fibrotic osseointegration (bone formation) failure” results in implant loosening that requires revision surgeries, eventually leading to a higher risk of failure and additional economic burden on public health systems (Brånemark et al., 2014; Thomson et al., 2019). For young U.S. military Service members with limb amputation, an expedited return to an active lifestyle is essential in order to limit muscle atrophy, mental health concerns, and a poor quality of life (Hansson, Hagberg, Cawson, and Brodtkorb, 2018; Wasser, Vincent, Herman, and Vincent, 2019). However, the current protocols for bone-anchored limbs require a prolonged period, from a few months to as long as 1 year between implantation and full weight-bearing to lower the risk of implant loosening (Thesleff, Brånemark, Håkansson, and Ortiz-Catalan, 2018). Due to this same concern of implant loosening, many patients are excluded from receiving bone-anchored limbs that, if successful, would have many advantages over the conventional sockets. Innovation: Our novel model of osseointegration failure enables our laboratory to ask scientifically rigorous questions aimed to improve the care delivered to patients. Our objective is to use animal models to explore the use of non-surgical therapeutic interventions based on the injections of intermittent Parathyroid Hormone (iPTH), an FDA-approved agent, which would allow for rapid clinical translation of our findings. We will use genetically manipulated models to track cells as they change and lead to implant loosening. Until now, no specific cell types have been identified as responsible for this debilitating situation. Identification of these cell populations and the mechanisms driving them to produce fibrosis will allow for the development of the first non-surgical therapeutic agent against implant loosening. Additionally, this work will also provide new perspective for the research on other fibrotic diseases across various organs, e.g., pulmonary fibrosis. Applicability and Impact: If successful, our proposal will provide targets for the diagnosis, prevention, and treatment of early implant loosening of bone-anchored limbs. The injectable biologic iPTH would represent the first non-surgical management option for implant loosening. Because iPTH has been approved by FDA for the treatment of osteoporosis, its use as a therapy for implant loosening can be rapidly tested with a sequential clinical trial. The biomarkers identified in this project will allow us to identify patients who are at risk-for implant loosening and develop an approach whereby patients can be treated prior to surgery or at early post-operative stage to reduce likelihood of implant failure. By ensuring the reliable function of bone-anchored limb, we will be able to allow more patients to receive this procedure, which has numerous potential advantages over the conventional sockets. We will also be able to shorten and simplify the post-operative rehabilitation and ena
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110900
Entities
People
- Xu Yang
Organizations
- Hospital for Special Surgery
- United States Army