Alterations in compositional and cellular properties of the subchondral bone are linked to cartilage degeneration in hip osteoarthritis

Objective The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. Method Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. Results In hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7±4.5 mm -1 , OA: 16.4±10.2 mm -1 , age-adjusted mean difference 10.5 mm -1 [95% CI 4.7 to 16.4], p <0.001) but a similar number of osteoclasts compared to controls ( p =0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8±0.2 wt%, OA: 3.1±0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p =0.011) and lower tissue hardness (controls: 0.69±0.06 GPa, OA: 0.67±0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p =0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R 2 adjusted=0.561, p <0.001). Conclusion Subchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. Data and materials availability All data are available in the main text or the supplementary materials.