Background 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. Method 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. Results 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. Conclusion 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.

Objective. To assess the impact of a computerized system on physicians’ accuracy and agreement rate, as compared with unaided diagnosis. Methods. A set of 124 unilateral knee radiographs from the Osteoarthritis Initiative (OAI) study were analyzed by a computerized method with regard to Kellgren-Lawrence (KL) grade, as well as joint space narrowing, osteophytes, and sclerosis Osteoarthritis Research Society International (OARSI) grades. Physicians scored all images, with regard to osteophytes, sclerosis, joint space narrowing OARSI grades and KL grade, in 2 modalities: through a plain radiograph ( unaided) and a radiograph presented together with the report from the computer assisted detection system ( aided). Intraclass correlation between the physicians was calculated for both modalities. Furthermore, physicians’ performance was compared with the grading of the OAI study, and accuracy, sensitivity, and specificity were calculated in both modalities for each of the scored features. Results. Agreement rates for KL grade, sclerosis, and osteophyte OARSI grades, were statistically increased in the aided versus the unaided modality. Readings for joint space narrowing OARSI grade did not show a statistically difference between the 2 modalities. Readers’ accuracy and specificity for KL grade >0, KL >1, sclerosis OARSI grade >0, and osteophyte OARSI grade >0 was significantly increased in the aided modality. Reader sensitivity was high in both modalities. Conclusions. These results show that the use of an automated knee OA software increases consistency between physicians when grading radiographic features of OA. The use of the software also increased accuracy measures as compared with the OAI study, mostly through increases in specificity.

Objective: Joint space width (JSW) has been the gold standard to assess loss of cartilage in knee osteoarthritis (OA). Here we describe a novel quantitative measure of joint space width: standardized JSW (stdJSW). We assess the performance of this quantitative metric for JSW at tracking Osteoarthritis Research Society International (OARSI) joint space narrowing grade (JSN) changes and provide reference values for different JSN grades and their annual change. Methods: We collected 18,934 individual knee images along with JSW and JSN readings from baseline up to month 48 (4 follow-ups) from the OAI study. Standardized JSW and 12-month JSN grade changes were calculated for each knee. For each JSN grade and 12-month grade change, the distribution of JSW loss was calculated for JSW and stdJSW. Area under the ROC curves was calculated on discrimination between different JSN grades for JSW and stdJSW. Standardized response mean (SRM) was used to compare the responsiveness of the two measures to changes in JSN grade. Results: The areas under the receiver operating characteristic (ROC) curve (AUC) for stdJSW at discriminating between successive JSN grades were AUC stdJSW ¼ 0.87, 0.95, and 0.96, for JSN>0, JSN>1 and JSN>2, respectively, whereas these were AUC fJSW ¼ 0.79, 0.90, 0.98 for absolute JSW. We find that standardized JSW is significantly more responsive than absolute JSW, as measured by the SRM. Conclusions: Our results show that stdJSW outperforms absolute JSW at discriminating and tracking changes in JSN and further that this effect is in part because stdJSW cancels JSW variations attributed to patient height variations.

Objective To evaluate the clinical applicability of a software tool developed to extract bone textural information from conventional lumbar spine radiographs, and to test it in a subset of postmenopausal women treated for osteoporosis with the fully human monoclonal antibody denosumab. Methods The software was developed based on the principles of a fractal model using pixel grey-level variations together with a specific machine-learning algorithm. The obtained dimensionless parameter, termed bone structure value (BSV), was then tested and compared to bone mineral density (BMD) in a sub-cohort of postmenopausal women with osteoporosis who were treated with the monoclonal antibody denosumab, within the framework of a large randomized controlled trial and its open-label extension phase. Results After 3 years and after 8 years of treatment with denosumab, mean lumbar spine BMD as well as mean lumbar BSV were significantly higher compared to study entry (one-way repeated measures ANOVA for DXA: F = 108.2, p < 0.00001; and for BSV: F = 84.3, p < 0.00001). The overall increase in DXA-derived lumbar spine BMD at year 8 was + 42% (mean ± SD; 0.725 ± 0.038 g/cm 2 to 1.031 ± 0.092 g/cm 2 ; p < 0.0001), and the overall increase of BSV was 255% (mean ± SD; 0.076 ± 0.022 to 0.270 ± 0.09, p < 0.0001). Overall, BMD and BSV were significantly correlated ( R = 0.51; p < 0.0001). Conclusions This pilot study provides evidence that lumbar spine BSV as obtained from conventional radiographs constitutes a useful means for the assessment of bone-specific treatment effects in postmenopausal women with osteoporosis.

The relationship between knee osteoarthritis progression and changes in tibial bone structure has long been recognized and various texture descriptors have been proposed to detect early osteoarthritis (OA) from radiographs. This work aims to investigate (1) femoral textures as an OA indicator and (2) the potential of entropy as a computationally efficient alternative to established texture descriptors. We design a robust semi-automatically placed layout for regions of interest (ROI), compute the Hurst coefficient and the entropy in each ROI, and employ statistical and machine learning methods to evaluate feature combinations. Based on 153 high-resolution radiographs, our results identify medial femur as an effective univariate descriptor, with significance comparable to medial tibia. Entropy is shown to contribute to classification performance. A linear five-feature classifier combining femur, entropic and standard texture descriptors, achieves AUC of 0.85, outperforming the state-of-the-art by roughly 0.1.