The new single-blind, randomized, pilot, clinical trial, part of the Arthritis Foundation 2023 FastOA Interventional Pilot Studies, will harness the expertise of surgeons, radiologists, biostatisticians, and cellular and molecular biologists to determine whether cBMA may prevent the chronic inflammation that can lead to pain and stiffness following surgery, and can also contribute to post-traumatic osteoarthritis. Previous studies have suggested that cBMA injections may improve surgical outcomes, but this approach has not yet been evaluated in rigorous clinical trials in patients undergoing ACL revision surgery.

The cBMA used in these procedures is the patient’s own and is collected from the pelvic bones. The participating patients will be randomized to receive either cBMA injections at the time of revision surgery or standard care.

The goal of the trial is not only to establish whether the addition of cBMA reduces the risk of PTOA, but also to understand the underlying mechanisms of cBMA therapy and to look for biomarkers in the joint microenvironment that might help to refine the approach and further improve outcomes. Given the lack of effective non-surgical interventions for the prevention and treatment of PTOA, this study is expected to provide valuable insights that could guide care in the future.

To determine whether any differences observed between the two arms of the trial are clinically meaningful, the primary measure of the treatment’s success will be the patients' self-reported pain levels 12 months after surgery. This will be determined by using the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain. As a secondary measure, the investigators will deploy advanced, quantitative MRI scans to look for changes in the cartilage. “We will leverage clinical outcomes and imaging to evaluate the efficacy of adding cBMA to standard treatment,” said co-primary investigator Miguel Otero, PhD, scientist in the Orthopedic Soft Tissue Research Program, co-director of the Derfner Foundation Precision Medicine Laboratory, and of the HSS Research Institute Histopathology Service.

“Depending on what we learn about whether cBMA reduces the risk of PTOA, the results generated by this study may have the potential to change clinical practice,” added co-primary investigator Scott Rodeo, MD, Vice Chair of Orthopaedic Research, co-director of the Orthopaedic Soft Tissue Research Program, and director of the Center for Regenerative Medicine at HSS.

By analyzing the cellular and molecular make-up of the cBMA as well as synovial fluids collected during and after the ACL revision surgery, the investigators also hope to gain insight into the populations of immune cells present within the joint microenvironment and the link between certain immune components and clinical outcomes. The researchers hypothesize that cBMA’s functionally relevant immune-modulatory and disease-modifying effects depend on the fluid’s cellular and molecular composition. They expect that these biospecimens may yield clues about how to further improve patient outcomes.

The FastOA2023 trial will harness strength of two Arthritis Foundation OACTN Clinical Trial Units that are also participating in the Post-Injury Knee Arthritis Severity Outcomes (PIKASO) Study and will use parallel instruments and dataset management. PIKASO is an ongoing, multicenter, randomized phase II clinical trial examining the use of metformin in patients who are at high-risk for developing PTOA in the knee after ACL reconstruction.

To learn more about the study and when enrollment opens in FastOA2023 visit clinicaltrials.gov. 

For a long time, physicians believed all bones formed in the same way – through a universal process of ossification. However, this study, led by primary investigator Matthew Greenblatt, MD, PhD, associate professor of pathology and laboratory medicine at Weill Cornell Medicine and assistant scientist in the HSS research division, alongside clinical collaborator Sravisht Iyer MD, spine surgeon at HSS, illuminated that certain vertebral skeletal stem cells play a unique and formative role in the development and life cycle of spinal vertebrae. Specifically, the investigators identified a stem cell that is responsible for bone formation in the vertebrae. Their research was made possible by support from a Pershing Square Foundation Cancer Research Prize and a special program established by the Anna-Maria and Stephen Kellen Foundation and Marina Kellen French, Vice President of the Foundation and an HSS trustee, that provides support for clinicians pursuing research as a significant component of their careers.

This significant finding carries profound implications for the field of spine health, including spinal healing, degeneration, treatment approaches, comprehension of degenerative spine disorders – and the potential to lead to breakthroughs in the prevention and treatment of vertebral osteoporosis and cancer metastasis.

“Understanding how vertebrae develop will help us more effectively treat patients, screen them before surgical intervention, and will ultimately lead to more effective preventive care and optimized bone health,” said Dr. Iyer. “The identification of this unique stem cell in the spine has the potential to significantly enhance our patients' outcomes in spine fusion surgery–a procedure performed hundreds of thousands of times in the United States each year–because it may allow for us to screen for problems ahead of time,” he continued. “The findings may also advance care for people with osteoporosis and, specifically, the 30 to 50 percent of the global population who suffer a vertebral fracture at some point in their lives.”

By manipulating bone-like “organoids” made from vertebral stem cells, this study also explored the disparities in metastasis rates between spinal bones and long bones, which include bones of the thigh, leg, arm and forearm. "Traditionally, it was believed that cancer cells were attracted to the spine due to directed blood flow. However, our discovery of this vertebral stem cell provides a likely explanation of why some cancers most often spread to the spine,” stated Dr. Greenblatt. “We predict this discovery will lead to the targeting of these cells to disrupt the function and ultimately reduce the spread of cancer to the spine."

The research team for this study included Jun Sun, PhD, first author and a postdoctoral associate at Weill Cornell; Kyle Morse, MD, an orthopedic surgery resident at HSS; and Lingling Hu, PhD, researcher at HSS, and has implications extending far beyond the laboratory and has the potential to impact patient care worldwide. Armed with insights into spine development and evolution, physicians will be able to tailor treatments and surgical intervention with more precision, with hope for improved patient outcomes across the board.