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Reduction of subchondral bone marrow lesions concurrent with early recovery of trabecular bone mineral density in knee osteoarthritis following RANKL inhibitor administration for the treatment of osteoporosis: Implying human osteoporotic osteoarthritis?

Chao Sun,Hao Lin,Yuan Xue,Zequn Zhang,Rongzhi Ma,Zhixin Lin,Jia-ming Zhou

Published 2025 in Seminars in Arthritis & Rheumatism

ABSTRACT

OBJECTIVE To illustrate the correlation between the reduction of subchondral bone marrow lesions (BMLs) and the early recovery of trabecular bone mineral density (TBMD) in symptomatic knee osteoarthritis (KOA) patients. METHODS A RANKL inhibitor was applied to osteoporosis (OP) patients who also had symptomatic KOA and BMLs and whose knee symptoms were refractory to NSAID therapy. Clinical symptoms, HRQoL, BMLs, knee TBMD, systemic BMD, and bone turnover markers were evaluated within a 6-month follow-up. The correlation between early TBMD recovery and BML reduction was explored. RESULTS Following a RANKL inhibitor application: (1) At the first-week follow-up, clinical symptoms were relieved and persisted until the final follow-up; HRQoL showed improvement. (2) BMLs and TBMD progressively improved at 4-week and 3-month follow-ups; the bone turnover markers significantly decreased. (3) Systemic BMD improved at the 6-month follow-up. (4) At the 3-month follow-up, the reduction in subchondral BML areas positively correlated with the increase in CT-HU values (r = 0.329; BML areas reduction: 173.09 ± 45.23 mm²; CT-HU values increase: 23.72 ± 3.77). CONCLUSION In this clinical study, after the application of a RANKL inhibitor for OP treatment, BMLs and knee pain were effectively reduced in OP patients with symptomatic KOA and BMLs. In addition, the correlation between early recovery of TBMD and reduction in BML area was also demonstrated. This study supports the concept of osteoporotic osteoarthritis (OPOA) and highlights the potential of subchondral bone as a target for KOA treatment.

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