There are no structure modifying treatments in osteoarthritis (OA) in part because the proof of structure modification requires large scale long term studies that demonstrate treatment effects on cartilage morphology or other joint structures. Also, changes in cartilage morphology may be irreversible. If biomarkers for treatment response were available, promising treatments could be tested efficiently and might be evaluated when disease is reversible. Without ways of detecting treatment effects, OA treatment development will likely continue to be delayed. To develop biomarkers for treatment response, biomarkers need to be tested using an effective treatment. Bariatric surgery (BSX) produces dramatic improvements in OA symptoms and likely results in stability of cartilage matrix or even improvement. With loss of 100 pounds over one year on average, in many but not all patient?s knee pain resolves. The assumption behind the planned work is that the weight loss that accompanies BSX constitutes a human model of an effective knee OA treatment which either stabilizes or leads to improvement in knee structure. That model will allow us to explore how detect this improvement in structure which might exemplify structure modification and might allow other treatments to be evaluated over a short-term basis. Structural changes in cartilage that reflect abnormal cartilage can now be imaged using several different approaches including T1rho and T2 mapping. Bone marrow lesions which show bone damage histologically and occur in regions of increased loading could improve with weight loss and could be a biomarker also. The overall goals of this project are to study massive weight loss from BSX and its effects on knee pain and structural pathology in knees.
The specific aims are: 1) To determine whether the improvement in knee pain in those experiencing weight loss after BSX is less likely in those with specific structural findings. 2) To characterize MRI changes before and one year after massive weight loss and in comparably obese persons not undergoing BSX. We will examine changes in imaged structure of cartilage using T1rho, T2 maps and bone marrow lesion volume.

Public Health Relevance

The development of treatments for osteoarthritis that prevent disease progression has been inhibited by our lack of knowledge as to what structural features to measure and which ones might be stabilized. The proposed study examines a group of knee pain patients undergoing bariatric surgery which leads to marked improvement, hoping that this condition will provide an example of which structural features might improve or stabilize when there is actually an effective treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR047785-12
Application #
8511567
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
2013-08-01
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
12
Fiscal Year
2013
Total Cost
$282,807
Indirect Cost
$139,844
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Emmanuel, K; Quinn, E; Niu, J et al. (2016) Quantitative measures of meniscus extrusion predict incident radiographic knee osteoarthritis--data from the Osteoarthritis Initiative. Osteoarthritis Cartilage 24:262-9
Neogi, Tuhina; Felson, David T (2016) Osteoarthritis: Bone as an imaging biomarker and treatment target in OA. Nat Rev Rheumatol 12:503-4
Øiestad, Britt Elin; White, Daniel K; Booton, Ross et al. (2016) Longitudinal Course of Physical Function in People With Symptomatic Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 68:325-31
Lu, Na; Dubreuil, Maureen; Zhang, Yuqing et al. (2016) Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study. Ann Rheum Dis 75:547-51
Misra, Devyani; Peloquin, Christine; Kiel, Douglas P et al. (2016) Intermittent Nitrate Use and Risk of Hip Fracture. Am J Med :
Felson, D T; Niu, J; Neogi, T et al. (2016) Synovitis and the risk of knee osteoarthritis: the MOST Study. Osteoarthritis Cartilage 24:458-64
Carlesso, Lisa C; Segal, Neil; Curtis, Jeffrey R et al. (2016) Knee Pain Severity Rather Than Structural Damage is a Risk Factor for Incident Widespread Pain: The Multicenter Osteoarthritis (MOST) Study. Arthritis Care Res (Hoboken) :
Guermazi, Ali; Hayashi, Daichi; Roemer, Frank W et al. (2016) Partial- and Full-thickness focal cartilage defects equally contribute to development of new cartilage damage in knee osteoarthritis - the Multicenter Osteoarthritis Study. Arthritis Rheumatol :
Dai, Zhaoli; Lu, Na; Niu, Jingbo et al. (2016) Dietary intake of fiber in relation to knee pain trajectories. Arthritis Care Res (Hoboken) :
Nguyen, Uyen-Sa D T; Zhang, Yuqing; Louie-Gao, Qiong et al. (2016) The Obesity Paradox in Recurrent Attacks of Gout in Observational Studies: Clarification and Remedy. Arthritis Care Res (Hoboken) :

Showing the most recent 10 out of 370 publications