QUANTITATIVE CT OF THE KNEE IN THE IMI-APPROACH OSTEOARTHRITIS COHORT: ASSOCIATION OF BONE MINERAL DENSITY WITH KELLGREN-LAWRENCE GRADES AND MENISCAL EXTRUSION

Abstract

The Innovative Medicines Initiative - Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) consortium is an exploratory, European, 5-centre, 2-year prospective follow-up cohort project to combine conventional and new disease markers and to identify different OA phenotypes. IMI-APPROACH was designed to prospectively describe pre-identified progressor phenotypes of patients with symptomatic and/or structural knee OA by use of conventional and novel clinical, imaging, and biochemical biomarkers, and to validate and refine a predictive model for progressor phenotypes based on these markers. Imaging parameters used to assess structural progression include quantitative CT (QCT), X-ray, quantitative MRI and semiquantitative MRI scoring of features of OA. To describe baseline cross-sectional periarticular CT-derived bone mineral density (BMD) measures in the IMI-APPROACH cohort at the knee and to analyze its association with structural disease severity and with meniscal extrusion. 297 people with knee OA were included in the APPROACH cohort study (age: 66.5±7.1 years, BMI: 28.1±5.3 kg/m², 77.5% women). QCT, MRI and X-ray examinations were performed at study inclusion. QCT scans were analyzed with MIAF-Knee to assess BMD at the femur (F) and tibia (T), each at the cortical bone plate (Cort) and at the epiphysis at three different locations: subchondral (Sub), at the mid-epiphysis (Mid) and adjacent to the metaphysis (Juxta). BMD was evaluated separately for each compartment (medial, lateral) and for the articular surfaces covered and not covered by the meniscus. Radiographs were evaluated according to Kellgren and Lawrence (KL) score. The MRI protocols included triplanar proton density-weighted fat-suppressed and a coronal T1-weighted sequence. MRI evaluation was performed using the semi-quantitative MOAKS instrument assessing meniscal extrusion. Meniscal extrusion is scored from 0 to 3 in the coronal plane. Comparisons of BMD at the different anatomical locations were performed using an analysis of variance (ANOVA). For the comparison of corresponding medial and lateral anatomic locations a paired t-test was used. An ANOVA with Bonferroni post hoc test was employed for analyzing the relation of KL score and meniscal extrusion with ipsicompartmental BMD. Results are presented as mean and standard deviation. Complete datasets of 275 patients were available for CT measures and MOAKS readings. 52 knees were KL 0, 71 KL 1, 62 KL 2, 79 KL 3 and 11 KL 4. Any medial meniscal extrusion (grade ≥ 1) was present in 162, any lateral extrusion in 44 patients. Mean BMD differed significantly between each anatomic location at both the femur and tibia (F: Cort 460.0 ± 59.5, Sub 250.6 ± 48.3, Mid 186.6 ± 44.5, Juxta 146.9 ± 39.9 mg/cm 3 , p<001; T: Cort 428.4 ± 55.5, Sub 225.1 ± 45.3, Mid 153.5 ± 44.5, Juxta 113.5 ± 34.5 mg/cm 3 ). At the tibia, all anatomic locations showed higher BMD at the medial articular surface (p<0.001) compared to the corresponding lateral one. At the femur higher BMD was observed for medial Cort and at the lateral Sub, Mid and Juxta locations compared to the corresponding other compartment (p<0.001). Tibial areas (medial and lateral) covered with meniscus showed lower BMD at Sub (p<0.001), equivalent BMD at Mid (p=0.07) and higher BMD at Juxta (p<0.001) compared to areas not covered with meniscus. Knees with KL3 and KL4 presented with higher Cort BMD at the tibia compared to KL0 (p=0.032, p<0.001). At the femur Sub BMD in KL2 only and Mid BMD in KL4 only were reduced compared to corresponding location in KL 0 knees (p=0.046, p=0.03). Medial meniscal extrusion grade 2 and 3 revealed increased BMD at the medial tibial Cort (p<0.001, p=0.007) compared to patients without extrusion. Only medial extrusion grade 3 showed increased BMD also at the medial femoral Cort (p=0.02) compared to those without. Lateral meniscal extrusion grade 3 showed increased BMD at the lateral Cort and Sub (p<0.001, p<0.001) tibia and at the lateral Cort (p<0.001) femur compared to those without extrusion. BMD within the epiphyses of the tibia and femur decreases with increasing distance from the joint. More severe structural OA, shows increased BMD values at the tibia and BMD decrease at the femur in some locations. Ipsicompartimental increase of femoral and tibial BMD is observed in compartments with meniscal extrusion grade 2and 3. This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115770, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. See www.imi.europa.eu and www.approachproject.eu . FWR is shareholder of Boston Imaging Core Lab. (BICL),LLC. And is consultant to Calibr and Grünenthal; MK reports grants from IMI-APPROACH, grants from Dutch Arthritis Association, during the conduct of the study; other from GlaxoSmithKline, Pfizer, Merck-Serono, Kiniksa, Abbvie, outside the submitted work; FJB reports grants from Gebro Pharma, grants from BIOIBERICA, grants from AB Science, grants from Abbvie, grants from Ablynx N.V., grants from Amgen, grants from Archigen Biotech Limited, grants from Boehringer, grants from Bristol-Myers, grants from Celgene Int., grants from Eli Lilly and Company, grants from F. Hoffmann- La Roche, grants from Galapagos, grants from Gedeon, grants from Genentech, grants from Gideal Sciences, NC, grants from Glaxosmithkline, grants from Hospira, grants from INC Research UK, grants from Inventiv Health Clinical, grants from Janssen, grants from Lilly, grants from Nichi-IKO Pharmaceutical, grants from Novartis, grants from ONO Pharma, grants from Pfizer, grants from Pharmaceutical Research, grants from Regeneron, grants from Roche, grants from SA UCB Pharma, grants from Sanofi, grants from TRB Chemedica, grants from UCB Biosciences GMBH, outside the submitted work; IKH reports personal fees from AbbVie, grants from Pfizer, outside the submitted work; FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma CORRESPONDENCE ADDRESS: frank.roemer@uk-erlangen.de