Imaging biomarkers permit improved approaches to identify the most at-risk patients encountering knee osteoarthritis (KOA) progression. This study aimed to investigate the utility of trabecular bone texture (TBT) extracted from plain radiographs, associated with a set of clinical, biochemical, and radiographic data, as a predictor of long-term radiographic KOA progression. We used data from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium dataset. The reference model made use of baseline TBT parameters adjusted for clinical covariates and radiological scores. Several models based on a combination of baseline and 24-month TBT variations (TBT∆TBT) were developed using logistic regression and compared to those based on baseline-only TBT parameters. All models were adjusted for baseline clinical covariates, radiological scores, and biochemical descriptors. The best overall performances for the prediction of radio-symptomatic, radiographic, and symptomatic progression were achieved using TBT∆TBT parameters solely, with area under the ROC curve values of 0.658 (95% CI: 0.612-0.705), 0.752 (95% CI: 0.700-0.804), and 0.698 (95% CI: 0.641-0.756), respectively. Adding biochemical markers did not significantly improve the performance of the TBT∆TBT-based model. Additionally, when TBT values were taken from the entire subchondral bone rather than just the medial, lateral, or central compartments, better results were obtained.

Trabecular bone texture (TBT) analysis has been identified as an imaging biomarker that provides information on trabecular bone changes due to knee osteoarthritis (KOA). In parallel with the improvement in medical imaging technologies, machine learning methods have received growing interest in the scientific osteoarthritis community to potentially provide clinicians with prognostic data from conventional knee X-ray datasets, in particular from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST) cohorts.
This study included 1888 patients from OAI and 683 patients from MOST cohorts. Radiographs were automatically segmented to determine 16 regions of interest. Patients with an early stage of OA risk, with Kellgren and Lawrence (KL) grade of 1 < KL < 4, were selected. The definition of OA progression was an increase in the OARSI medial joint space narrowing (mJSN) grades over 48 months in OAI and 60 months in MOST. The performance of the TBT-CNN model was evaluated and compared to well-known prediction models using logistic regression.
The TBT-CNN model was predictive of the JSN progression with an area under the curve (AUC) up to 0.75 in OAI and 0.81 in MOST. The predictive ability of the TBT-CNN model was invariant with respect to the acquisition modality or image quality. The prediction models performed significantly better with estimated KL (KLprob) grades than those provided by radiologists. TBT-based models significantly outperformed KLprob-based models in MOST and provided similar performances in OAI. In addition, the combined model, when trained in one cohort, was able to predict OA progression in the other cohort.
The proposed combined model provides a good performance in the prediction of mJSN over 4 to 6 years in patients with relevant KOA. Furthermore, the current study presents an important contribution in showing that TBT-based OA prediction models can work with different databases.

Trabecular bone texture analysis (TBTA) has been identified as an imaging biomarker that provides information on trabecular bone changes due to knee osteoarthritis (KOA). Consequently, it is important to conduct a comprehensive review that would permit a better understanding of this unfamiliar image analysis technique in the area of KOA research. We examined how TBTA, conducted on knee radiographs, is associated to (i) KOA incidence and progression, (ii) total knee arthroplasty, and (iii) KOA treatment responses. The primary aims of this study are twofold: to provide (i) a narrative review of the studies conducted on radiographic KOA using TBTA, and (ii) a viewpoint on future research priorities.
Literature searches were performed in the PubMed electronic database. Studies published between June 1991 and March 2020 and related to traditional and fractal image analysis of trabecular bone texture (TBT) on knee radiographs were identified.
The search resulted in 219 papers. After title and abstract scanning, 39 studies were found eligible and then classified in accordance to six criteria: cross-sectional evaluation of osteoarthritis and non-osteoarthritis knees, understanding of bone microarchitecture, prediction of KOA progression, KOA incidence, and total knee arthroplasty and association with treatment response. Numerous studies have reported the relevance of TBTA as a potential bioimaging marker in the prediction of KOA incidence and progression. However, only a few studies have focused on the association of TBTA with both OA treatment responses and the prediction of knee joint replacement.
Clear evidence of biological plausibility for TBTA in KOA is already established. The review confirms the consistent association between TBT and important KOA endpoints such as KOA radiographic incidence and progression. TBTA could provide markers for enrichment of clinical trials enhancing the screening of KOA progressors. Major advances were made towards a fully automated assessment of KOA.

To evaluate whether trabecular bone texture (TBT) parameters measured on computed radiographs (CR) could predict the onset of radiographic knee osteoarthritis (OA).
Subjects from the Osteoarthritis Initiative (OAI) with no sign of radiographic OA at baseline were included. Cases that developed either a global radiographic OA defined by the Kellgren-Lawrence (KL) scale, a joint space narrowing (JSN) or tibial osteophytes (TOS) were compared with the controls with no changes after 48 months of follow-up. Baseline bilateral fixed flexion CR were analyzed using a fractal method to characterize the local variations. The prediction was explored using logistic regression models evaluated by the area under the receiver operating characteristic curves (AUC).
From the 344 knees, 79 (23%) developed radiographic OA after 48 months, 44 (13%) developed progressive JSN and 59 (17%) developed osteophytes. Neither age, gender and BMI, nor their combination predicted poorer KL (AUC 0.57), JSN or TOS (AUC 0.59) scores. The inclusion of the TBT parameters in the models improved the global prediction results for KL (AUC 0.69), JSN (AUC 0.73) and TOS (AUC 0.71) scores.
Several differences were found between the models predictive of three different outcomes (KL, JSN and TOS), indicating different underlying mechanisms. These results suggest that TBT parameters assessed when radiographic signs are not yet apparent on radiographs may be useful in predicting the onset of radiological tibiofemoral OA as well as identifying at-risk patients for future clinical trials.

To examine whether trabecular bone texture (TBT) parameters assessed on computed radiographs could predict knee osteoarthritis (OA) progression.
This study was performed using data from the Osteoarthritis Initiative (OAI). 1647 knees in 1124 patients had bilateral fixed flexion radiographs acquired 48 months apart. Images were semi-automatically segmented to extract a patchwork of regions of interest (ROI). A fractal texture analysis was performed using different methods. OA progression was defined as an increase in the joint space narrowing (JSN) over 48 months. The predictive ability of TBT was evaluated using logistic regression and receiver operating characteristic (ROC) curve. An optimization method for features selection was used to reduce the size of models and assess the impact of each ROI.
Fractal dimensions (FD\'s) were predictive of the JSN progression for each method tested with an area under the ROC curve (AUC) up to 0.71. Baseline JSN grade was not correlated with TBT parameters (R < 0.21) but had the same predictive capacity (AUC 0.71). The most predictive model included the clinical covariates (age, gender, body mass index (BMI)), JSN and TBT parameters (AUC 0.77). From a statistical point of view we found higher differences in TBT parameters computed in medial ROI between progressors and non-progressors. However, the integration of TBT results from the whole patchwork including the lateral ROIs in the model provided the best predictive model.
Our findings indicate that TBT parameters assessed in different locations in the joint provided a good predictive ability to detect knee OA progression.