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October 15, 2020
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Targeting bone marrow lesions may reduce osteoarthritis pain

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Research linking fluctuations in bone marrow lesions with pain fluctuations may suggest that targeting these lesions could successfully reduce osteoarthritis pain, according to a speaker at the 2020 Congress of Clinical Rheumatology-West.

“With the use of MRI, where you can see more than just bone and tissues but also changes in soft tissue, it has indeed become clear that specific structural changes in a joint are associated with pain, and those are specifically bone marrow lesions, synovial thickening and synovial effusions,” Anne-Marie Malfait, MD, PhD, of Rush University Medical College in Chicago, told attendees at the virtual meeting. “Very importantly, it has been shown that fluctuations of these lesions are associated with fluctuations in pain, in as fast as over a period of about 6 weeks.”

KneePain
“Specific joint pathology, such as bone marrow lesions and synovitis, have been associated with knee pain and sensitization,” Anne Marie Malfait, MD, PhD, told attendees. Source: Adobe Stock

“This may really suggest that we can target bone marrow lesions if we want to reduce pain,” she added.

According to Malfait, this hypothesis has been tested in several proof-of-concept randomized, clinical trials, throughout the past 8 years. In one example, a randomized placebo-controlled clinical trial of intravenous zoledronate, administered to 59 participants, demonstrated a significant reduction in bone marrow lesions after 6 months. That study, published in the Annals of the Rheumatic Diseases in 2012, also showed a significant improvement in pain after 6 months, but this was not maintained for a full year.

Anne-Marie Malfait

Those results led to an ongoing study, the COAST-1 phase 3 trial of patients with OA and bone marrow lesions, which is evaluating zoledronic acid using MRI, Malfait said.

Meanwhile, another study, published in 2015 in the Annals of the Rheumatic Diseases, used patellofemoral braces to evaluate reduced bone marrow lesion volume in the patellofemoral joint, and its association with pain relief.

“This was a proof of concept study that demonstrated reduced bone marrow lesion volume in the patellofemoral joint was associated with reduced pain, without affecting the tibiofemoral bone marrow lesions,” Malfait said.

These findings, she added, feed into evidence supporting a strong peripheral drive for pain in OA.

According to Malfait, although researchers often speak of “central sensitization” when analyzing pain, rheumatologists should keep in mind that, clinically, the evidence suggests there is a strong peripheral drive for OA pain throughout the disease course.

Evidence for this includes research demonstrating that intra-articular local anesthetics can relieve pain, and that, in most cases, total joint replacements alleviate pain and normalize sensitization, she said.

“In addition, antibodies that neutralize the peripherally active nerve growth factor, which is solely peripherally active, show very pronounced analgesic effects,” Malfait said. “And lastly, specific joint pathology, such as bone marrow lesions and synovitis, have been associated with knee pain and sensitization.”