A recent phase 2a randomized, double-blind, placebo-controlled clinical trial has provided compelling evidence for the efficacy of denosumab in treating erosive hand osteoarthritis (OA). The study addressed a significant unmet need in the management of this debilitating condition, which has historically had limited therapeutic options.
The study, conducted over 48 weeks with 100 patients, demonstrated significant structural modification benefits of denosumab compared to placebo. The primary endpoint, change in the Ghent University Scoring System (GUSS) at week 24, was met with an estimated difference between groups of 8.9 (95% CI: 1.0 to 16.9; P=0.024), favoring denosumab. This effect was sustained and enhanced at week 48, with an estimated between-group difference of 14.3 (95% CI: 4.6 to 24.0; P=0.003). Notably, denosumab significantly reduced the odds of developing new erosive joints (OR: 0.24; 95% CI: 0.08 to 0.72; P=0.009) and demonstrated a favorable safety profile.
Osteoporotic fractures significantly contribute to morbidity and mortality, yet pharmacotherapy can effectively reduce fracture risk in high-risk individuals. Among antiresorptive drugs, denosumab stands out as a recently approved, fully human monoclonal antibody that targets and inhibits RANKL (receptor activator of NFκB ligand), a critical cytokine involved in bone turnover. By binding to RANKL with high specificity and affinity, denosumab inhibits osteoclast recruitment, maturation, and function, thereby reducing bone resorption. This mechanism contrasts with that of bisphosphonates, which bind to bone mineral and induce osteoclast apoptosis, leading to suppressed resorption. These mechanistic differences influence the onset and reversibility of treatment effects. Denosumab is particularly indicated for postmenopausal women with osteoporosis at high risk of fracture or for patients who have failed or are intolerant to other osteoporosis therapies. Clinical practice guidelines identify denosumab as a first-line option for preventing vertebral, hip, and non-vertebral fractures.
The drug is currently indicated for the management of osteoporosis and bone loss associated with cancer. Proof-of-concept studies have shown that it can delay the progression of erosive disease in rheumatoid arthritis patients, regardless of how well the disease activity is controlled. The current results suggest that denosumab has a significant structure-modifying effect in erosive hand OA, characterized by the promotion of joint remodeling and the prevention of new erosive lesions. The findings represent a potential advancement in the management of this challenging condition, providing a foundation for further research into RANKL inhibition as a therapeutic strategy in erosive OA.
References
- Liu X, Robbins S, Eyles J, Fedorova T, Virk S, Deveza LA, . Efficacy and safety of a supplement combination on hand pain among people with symptomatic hand osteoarthritis an internet-based, randomised clinical trial the RADIANT study. Osteoarthritis Cartilage. 2021 May;29(5):667-677.
- Hanley DA, Adachi JD, Bell A, Brown V. Denosumab: mechanism of action and clinical outcomes. Int J Clin Pract. 2012 Dec;66(12):1139-46.