2013 IR&D Annual Report

MicroCT Investigation of Relationships in Bone-cartilage Structure, 18-R8399

Principal Investigators
Todd L. Bredbenner
Daniel P. Nicolella

Inclusive Dates: 06/26/13 – 10/28/13

Background — Osteoarthritis (OA) is the most common form of arthritis and the major cause of activity limitation and physical disability in older people. Osteoarthritis most often occurs in the hands (at the ends of the fingers and thumbs), spine (neck and lower back), knees and hips. Arthritis causes pain, swelling and reduced motion in joints caused by the breakdown or degradation of the articular cartilage covering the joint surfaces. It is widely believed that OA results from the local mechanical environment of the joint in general, and in the cartilage in particular, in combination with systemic susceptibility to the disease. However, many individuals who do not have these risk factors will go on to develop the disease later in life. This has led to the hypothesis that slight differences in joint mechanics, driven by variability in joint anatomy, along with biological and genetic predisposition, lead some individuals to develop OA while others do not. Previous collaboration with Texas Biomedical Research Institute (TxBiomed) has shown that knee OA occurs commonly and naturally in male and female adult baboons. The roles of cartilage degeneration and the underlying subchondral bone in the onset and progression of osteoarthritis have been the subject of much debate over the past several decades due to the disparate treatment pathways that are associated.

Approach — The objective of this project was to characterize the spatial relationship between cartilage thickness and defects and the composition of the underlying subchondral bone in baboon knees from a small subset of 30 age-matched females: 10 were unaffected by OA, 10 had early stage OA, and 10 had moderate OA disease. The left, distal femur of 30 baboons was imaged using micro-computed tomography (microCT). Bone and cartilage components were identified in the imaging data for each individual and image intensity values in the microCT data for bones were converted to bone mineral density values. Statistical shape and trait modeling methods (partly developed under internal research projects 18-R8039, 18-R8072, and 18-R9541) were used to describe the spatial variation in cartilage thickness and adjacent bone density characteristics for each distal femur.

Accomplishments — SwRI researchers demonstrated their ability to image and characterize knee cartilage and adjacent bony tissue from baboons and, despite small sample sizes, demonstrated the ability to differentiate between OA status using a characterization of the cartilage-subchondral bone interface. The results from this project, along with other data previously collected at TxBiomed (in collaboration with SwRI), form the basis for justifying the baboon as a model of the human osteoarthritic condition and allow the pursuit of targeted funding opportunities within the National Institutes of Health (NIH) and with commercial pharmaceutical and imaging clients. SwRI believes that this now existing body of preliminary data will open up a new area of research that can be applied to pre-clinical drug development, genetic analysis of OA susceptibility, and assessment of osteoarthritis risk, incidence, and progression from clinical MRI and contrast-enhanced CT data. Researchers expect that results obtained from larger sample sizes of distal femurs and proximal tibias, will be proposed in response to a targeted NIH Program Announcement and will further elucidate the effects of OA involvement on the functional behavior of cartilage and the relationship with the adjacent subchondral bone.

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Southwest Research Institute® (SwRI®), headquartered in San Antonio, Texas, is a multidisciplinary, independent, nonprofit, applied engineering and physical sciences research and development organization with 9 technical divisions.