Osteoarthritis (OA) is an important public health problem as it is one of the most disabling diseases in the elderly but effective treatments are limited. It is, therefore, salient that no disease-modifying medical remedies for OA exist, even though an analogous age-related musculoskeletal disorder, osteoporosis, and benefits from several effective treatments. However, and in contrast to osteoporosis, there is no established biomarker to detect at-risk individuals at an early stage and to follow them over time. This has been a primary obstacle to the development of disease-modifying interventions for knee OA. Measurement of region-specific tibial periarticular bone mineral density (paBMD) is a novel utilization of dual energy X-ray absorptiometry (DXA) technology that has recently emerged with potential as a biomarker for knee OA. Importantly, DXA scanners are ubiquitous, easy to operate, relatively non-hazardous and inexpensive;further, quantitation of tibial paBMD can be performed quickly and is highly reproducible in the hands of well-trained technicians. Our goals are four fold: (1) to show that tibial paBMD as an indicator of risk for the development of OA on X-ray and related chronic pain, (2) to use sophisticated statistical methods to calculate the level of risk an individual has of developing knee OA (3) to determine whether tibial paBMD predicts longitudinal cartilage volume loss in knees that do not have OA, and (4) to test the association of tibial paBMD with features of OA in the peri-articular bone seen on MRI scans, such as bone attrition (flattening or depression of bone adjacent to cartilage) , bone marrow lesions (regions of high signal in the bone marrow seen on water sensitive MRI sequences), osteophytes and subchondral cysts. We will pursue these aims by proposing an ancillary project to the outstanding ongoing Osteoarthritis Initiative (OAI) Study that provides routine extensive annual evaluations including x-rays and 3-T MRI (but not yet DXA) in people at high risk for the development of knee OA. If we are able to show that tibial paBMD is a good biomarker for knee OA, this will take us an important step closer towards finding an effective disease-modifying treatment for knee OA.

Public Health Relevance

Osteoarthritis (OA) is an important public health problem as it is one of the most disabling diseases in the elderly but effective treatments are limited. If we are able to show that a knee bone density scan is a good biomarker for early knee OA, this will take us an important step closer towards finding an effective disease- modifying treatment for this condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR060718-01A1
Application #
8238434
Study Section
Special Emphasis Panel (ZRG1-DTCS-U (81))
Program Officer
Lester, Gayle E
Project Start
2012-09-01
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$459,870
Indirect Cost
$142,084
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
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Lo, Grace H; Strayhorn, Michael T; Driban, Jeffrey B et al. (2018) Subjective Crepitus as a Risk Factor for Incident Symptomatic Knee Osteoarthritis: Data From the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 70:53-60
Lo, Grace H; Merchant, Mehveen G; Driban, Jeffrey B et al. (2018) Knee Alignment Is Quantitatively Related to Periarticular Bone Morphometry and Density, Especially in Patients With Osteoarthritis. Arthritis Rheumatol 70:212-221
LaValley, Michael P; Lo, Grace H; Price, Lori Lyn et al. (2017) Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density. Arthritis Res Ther 19:95
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Lo, Grace H; McAlindon, Timothy E; Hawker, Gillian A et al. (2015) Symptom assessment in knee osteoarthritis needs to account for physical activity level. Arthritis Rheumatol 67:2897-904
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Pang, Jincheng; Driban, Jeffrey B; Destenaves, Geoffroy et al. (2013) Quantification of bone marrow lesion volume and volume change using semi-automated segmentation: data from the osteoarthritis initiative. BMC Musculoskelet Disord 14:3