Hand OA (HOA) is a painful, destructive and deforming polyarticular disorder that impairs an individual's ability to perform manipulative activities of daily life. Its high frequency and strong association with age has been the basis of attribution to inevitable joint degeneration, and of therapeutic nihilism. The severity of HOA can approach that of rheumatoid arthritis, yet in stark contrast to that rarer disorder has been the subject of little research and benefits from no treatments known to effect its development or progression. Involvement of hand joints is the commonest and most heritable manifestation of OA and is a sentinel for the `generalized' OA phenotype. While site-specific biomechanical factors are influential in its development, there is also evidence that bone health and constitutional factors predispose to incidence and progression of HOA. Risk of HOA is doubled in obese individuals, an association more plausibly attributable to systemic factors than the mechanical effect of overload. Indeed, recent epidemiological and clinical data indicate that metabolic syndrome rather than obesity has the greater impact on the initiation and severity of OA. The pathogenesis of metabolic syndrome and OA involve abnormalities in common metabolic intermediates, however, the relationship of these pathways to the development and progression of HOA has been explored to only a limited extent. Recent investigations also indicate that the structural basis for HOA is broader than cartilage loss alone, with distinct pathological pathways that include osteophytosis, marginal and central joint erosion. Also, there is clinical controversy about whether erosive HOA is a separate entity, or simply more advanced disease. We will analyze annually-collected longitudinal radiographic, covariate and outcome data, and biospecimens from the Osteoarthritis Initiative, the largest most comprehensive cohort study of OA, and perform semi- quantitative and computer-aided image measurements across multiple hand joints to evaluate and contrast the roles of structural and metabolic characteristics in the development of radiographic, symptomatic and erosive HOA.

Public Health Relevance

Hand OA (HOA) is a painful, destructive and deforming age-related polyarticular disorder that impairs an individual's ability to perform manipulative activites of daily life. While site-specific biomechanical factors are influential in its development, there s also evidence that bone health and constitutional factors associated with obesity predispose to incidence of radiographic and symptomatic HOA. Deeper understanding of these aspects will help us develop preventive and therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR066378-03
Application #
9245652
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Lester, Gayle E
Project Start
2015-04-01
Project End
2018-09-30
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2017
Total Cost
$643,624
Indirect Cost
$120,503
Name
Tufts University
Department
Type
Independent Hospitals
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Davis, Julie E; Schaefer, Lena F; McAlindon, Timothy E et al. (2018) Characteristics of Accelerated Hand Osteoarthritis: Data from the Osteoarthritis Initiative. J Rheumatol :
Schaefer, Lena F; McAlindon, Timothy E; Eaton, Charles B et al. (2018) The associations between radiographic hand osteoarthritis definitions and hand pain: data from the osteoarthritis initiative. Rheumatol Int 38:403-413
McAlindon, T; Roberts, M; Driban, J et al. (2018) Incident hand OA is strongly associated with reduced peripheral blood leukocyte telomere length. Osteoarthritis Cartilage 26:1651-1657