Imaging of cartilage and bone: promises and pitfalls in clinical trials of osteoarthritis

Abstract

summary Imaging in clinical trials is used to evaluate subject eligibility, and/or efficacy of intervention, supporting decision making in drug development by ascertaining treatment effects on joint structure. This review focusses on imaging of bone and cartilage in clinical trials of (knee) osteoarthritis. We narratively review the full-text literature on imaging of bone and cartilage, adding primary experience in the implementation of imaging methods in clinical trials. Aims and constraints of applying imaging in clinical trials are outlined. The specific uses of semi-quantitative and quantitative imaging biomarkers of bone and cartilage in osteoarthritis trials are summarized, focusing on radiography and magnetic resonance imaging (MRI). Studies having compared both imaging methodologies directly and those having established a relationship between imaging biomarkers and clinical outcomes are highlighted. To make this review of practical use, recommendations are provided as to which imaging protocols are ideal for capturing specific aspects of bone and cartilage tissue, and pitfalls in their usage are highlighted. Further, the longitudinal sensitivity to change, of different imaging methods is reported for various patient strata. From these power calculations can be accomplished, provided the strength of the treatment effect is known. In conclusion, current imaging methodologies provide powerful tools for scoring and measuring morphological and compositional aspects of most articular tissues, capturing longitudinal change with reasonable to excellent sensitivity. When employed properly, imaging has tremendous potential for ascertaining treatment effects on various joint structures, potentially over shorter time scales than required for demonstrating effects on clinical outcomes.

Greater Lateral Femorotibial Cartilage Loss in Osteoarthritis Initiative Participants With Incident Total Knee Arthroplasty: A Prospective Cohort Study

“…Magnetic resonance imaging (MRI) has been developed for quantitatively measuring structural progression of knee OA, by virtue of directly and accurately delineating articular cartilage and other synovial tissues (5, 6). Yet, regulatory guidance for the approval of disease modifying OA drugs (DMOADs) requests that reductions in structural pathology should be associated with improvements in clinical outcomes (5, 6).…”

Bone Area Provides a Responsive Outcome Measure for Bone Changes in Short-term Knee Osteoarthritis Studies

“…In this small, short-term study of people with OA knee selected for high risk of structural progression, 3D bone area using AAMs demonstrated change in 3 months for the medial femoral region, and for both femoral regions at 6 months. Previous analysis of this dataset did not demonstrate significant change in cartilage thickness (1), one of the most promising MRI biomarkers of OA progression to date (11).…”

Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis

“…Given the paucity of studies dealing with cartilage preservation, we could not perform a meta-analysis this time. Because long-term intervention by supplements with sufficient compliance is difficult in terms of compliance, we need a new method to evaluate the condition of cartilage within a short time period, such as evaluation by magnetic resonance imaging or using reliable fluid biomarkers [41, 42]. …”