Clinical rheumatology · 2026
Subchondral bone density and trabecular morphometry mediate the association between knee malalignment and osteophyte progression in osteoarthritis: data from the osteoarthritis initiative.
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Yuan Shiwen, Ruan Guangfeng, Wang Xiaodong, Lo Grace H, Wang Cuicui, Zhu Zhaohua, Xu Siqi, Li Weinian, Cai Xiaoyan, Hunter David J
Аннотация
OBJECTIVE: To investigate whether subchondral bone mediates the relationship between knee malalignment and osteophyte progression.
DESIGN: Data were obtained from the Osteoarthritis Initiative (OAI) and two ancillary imaging studies. Two analytic cohorts were defined by mediator type: a DXA cohort (periarticular bone mineral density [paBMD]) and an MRI cohort (trabecular morphometry: aBVF, aTb.N, aTb.Sp, aTb.Th). Alignment (hip-knee-ankle [HKA] angle) was assessed at either 12 or 24 months under the Lower Limb Alignment study; bone measures were obtained at either 30 or 36 months through the Bone Ancillary Study; and radiographic osteophyte scores were evaluated at baseline and 48 months. Knees were categorized into five alignment groups (neutral, mild/severe varus, mild/severe valgus). Analyses used generalized estimating equations and multivariable linear regression with non-parametric bootstrapping.
RESULTS: A total of 826 knees (DXA cohort) [ (mean age 61.9 years (SD 9.1), BMI 29.8 kg/m2 (SD 4.5); 60.5% female; 79.8% KL grade ≥ 2)] and 401 knees (MRI cohort) were analyzed. Only severe varus and valgus were associated with osteophyte progression. For severe varus, medial progression was mediated by higher medial paBMD and a higher medial-to-lateral (M:L) paBMD ratio, accounting for 20.3% and 70.7% of the total effect for the femur, and 23.2% and 65.4% for the tibia. Medial trabecular morphometry contributed to medial tibial progression, with indirect effects via higher aBVF (27.2%) and aTb.N (35.4%), and via lower aTb.Sp (12.2%). For severe valgus, lateral progression was mediated by higher lateral paBMD and a lower M:L paBMD ratio, accounting for 14.2% and 67.9% for the femur, and 9.3% and 40.7% for the tibia.
CONCLUSIONS: Compartment-specific bone measures partly mediate the association between static malalignment and osteophyte progression, suggesting that targeting bone may modify this longitudinal relationship. Key Points • Compartment-specific paBMD mediates the relationship between malalignment and osteophyte progression, with the M:L BMD ratio strengthening this effect more than either medial or lateral paBMD alone. • Medial trabecular morphometry partially mediates the varus alignment-osteophyte progression relationship. • Subchondral bone remodeling is locally driven by mechanical stress, as systemic measures like femoral neck BMD do not mediate the malalignment-osteophyte link.
DESIGN: Data were obtained from the Osteoarthritis Initiative (OAI) and two ancillary imaging studies. Two analytic cohorts were defined by mediator type: a DXA cohort (periarticular bone mineral density [paBMD]) and an MRI cohort (trabecular morphometry: aBVF, aTb.N, aTb.Sp, aTb.Th). Alignment (hip-knee-ankle [HKA] angle) was assessed at either 12 or 24 months under the Lower Limb Alignment study; bone measures were obtained at either 30 or 36 months through the Bone Ancillary Study; and radiographic osteophyte scores were evaluated at baseline and 48 months. Knees were categorized into five alignment groups (neutral, mild/severe varus, mild/severe valgus). Analyses used generalized estimating equations and multivariable linear regression with non-parametric bootstrapping.
RESULTS: A total of 826 knees (DXA cohort) [ (mean age 61.9 years (SD 9.1), BMI 29.8 kg/m2 (SD 4.5); 60.5% female; 79.8% KL grade ≥ 2)] and 401 knees (MRI cohort) were analyzed. Only severe varus and valgus were associated with osteophyte progression. For severe varus, medial progression was mediated by higher medial paBMD and a higher medial-to-lateral (M:L) paBMD ratio, accounting for 20.3% and 70.7% of the total effect for the femur, and 23.2% and 65.4% for the tibia. Medial trabecular morphometry contributed to medial tibial progression, with indirect effects via higher aBVF (27.2%) and aTb.N (35.4%), and via lower aTb.Sp (12.2%). For severe valgus, lateral progression was mediated by higher lateral paBMD and a lower M:L paBMD ratio, accounting for 14.2% and 67.9% for the femur, and 9.3% and 40.7% for the tibia.
CONCLUSIONS: Compartment-specific bone measures partly mediate the association between static malalignment and osteophyte progression, suggesting that targeting bone may modify this longitudinal relationship. Key Points • Compartment-specific paBMD mediates the relationship between malalignment and osteophyte progression, with the M:L BMD ratio strengthening this effect more than either medial or lateral paBMD alone. • Medial trabecular morphometry partially mediates the varus alignment-osteophyte progression relationship. • Subchondral bone remodeling is locally driven by mechanical stress, as systemic measures like femoral neck BMD do not mediate the malalignment-osteophyte link.