Disease-modifying OA drugs: Are we finally closing in?

By Lisa Marie BasileFact-checked by Barbara BekieszPublished April 28, 2026

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The reality is that joint replacement works well. But, avoiding a joint replacement should be our focus here.

—Cory Calendine, MD

Osteoarthritis management is still largely confined to symptom mitigation, highlighting a critical need for therapies that target the underlying biology of the disease.

—Harpreet Bawa, MD

Osteoarthritis (OA) treatment strategies have changed very slowly over the years, despite more than 500 million people living with the condition globally. ^[] To date, there are still no approved disease-modifying osteoarthritis drugs (DMOADs) for OA.

“While patients with rheumatoid arthritis or other autoimmune-driven pathologies have benefited from a revolution in biologic therapies that halt disease progression, osteoarthritis remains a challenge,” says Harpreet Bawa, MD, an orthopedic surgeon and joint replacement specialist. “Osteoarthritis management is still largely confined to symptom mitigation, highlighting a critical need for therapies that target the underlying biology of the disease.”

According to the Archives of Bone and Joint Surgery, this lack of DMOADs stems from a few characteristics of the existing drugs: adverse systemic effects, a short half-life in tissues when injected locally, and limited effectiveness. ^[]

The inflammatory signal

“OA is also very heterogeneous, meaning one patient’s arthritis is not identical to another’s, making research very difficult,” explains Stephen Stache, Jr., MD, FAMSSM, a non-operative sports medicine physician.

Fortunately, there’s been rekindled momentum in the OA field—driven largely by a better understanding of how the disease develops and progresses. ^[]

For example, researchers have found that OA isn’t just a wear-and-tear condition. Inflammation, rather, may be the key driver of progression.

Research in Immunity & Inflammation suggests that joint inflammation in OA is spurred on by an overactive immune response involving macrophages and T cells, along with inflammatory signaling molecules. ^[]

Are we getting any closer to a DMOAD for OA?

According to research presented at the recent Osteoarthritis Research Society International (OARSI) World Congress, we might be. ^[]

Researchers are currently trying to identify biomarker panels capable of stratifying knee OA patients into distinct pain subtypes. This should help improve patient selection for DMOAD trials. ^[]

But that’s not all. An abstract shared at OARSI focused on LLP2A-Ale—a novel peptide-drug conjugate combining an α4β1 integrin-binding ligand (LLP2A) with the bone-seeking bisphosphonate alendronate. LLP2A-Ale is designed to promote osteochondral repair and modulate inflammation as a DMOAD candidate. ^[]

“Disease-modifying drugs are one of the biggest unmet needs in musculoskeletal medicine,” says Dr. Stache. “There are promising candidates targeting inflammation pathways, cartilage regeneration, bone remodeling, and joint signaling pathways. Some agents have shown structural improvement or pain benefit in subgroups.”

These therapeutic agents can’t come soon enough—but they need to be effective, says Cory Calendine, MD, an orthopedic surgeon.

“If we find a drug that buys a 55-year-old another five or ten years before they need me, that changes lives,” he says. “If it only buys six months, the cost may never be justified. The reality is that joint replacement works well. But, avoiding a joint replacement should be our focus here.”

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