Multidimensional characterization and clinical profiling of subchondral bone endotypes in hip osteoarthritis

Treatment of osteoarthritis (OA) remains limited to symptom management and surgery without addressing pathophysiological or individual patient-specific factors. Here, we aimed to decipher whether individuals with hip OA can be stratified into endotypes based on multidimensional analysis of the subchondral bone and how these endotypes manifest clinically. Our overall goal was to establish a foundation for novel disease-modifying treatment strategies.

The study cohort consisted of 38 patients undergoing total hip arthroplasty who were assessed regarding clinical and radiographic features. Femoral heads were obtained during surgery and analyzed using a multidimensional approach. Principal component analysis and hierarchical clustering were performed using a variety of subchondral bone properties to classify patients into endotypes. Cluster configuration was selected based on silhouette width and cophenetic correlation.

We identified three clusters with respect to subchondral bone properties, characterized by I) low bone mass, low turnover; II) intermediate bone mass, high turnover, and III) high bone mass, high turnover. Cluster III also stood out as an osteocyte-rich endotype. Differences in subchondral microstructure, composition, and cellular activity were also reflected by variations in bone marrow adipose tissue, with high turnover endotypes exhibiting increased surrogates of lipolysis.

The consideration of subchondral bone endotypes may enable a personalized approach to the treatment of hip OA. Based on the respective cluster, subchondral homeostasis may be restored through targeted interventions, including the modulation of bone turnover, osteocytes, or bone marrow adipocytes, tailored to each endotype's unique profile, thereby laying the foundation for disease-modifying therapies.