Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis: The IDEA Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005). CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.
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In ten trials, a weight-reducing diet alone resulted in the desired weight loss, which consisted of fat mass as well as lean mass.
“In ten trials, a weight-reducing diet alone resulted in the desired weight loss, which consisted of fat mass as well as lean mass (290)(291)(292)(294)(295)(296)(297)(298)(299).”
From ESPEN practical guideline: Clinical nutrition and hydration in geriatrics (2022) · cites this paper as [294]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredFor several physical and strength-performance measures, greater improvements were observed in the combined groups than in the diet-only groups.
“Moreover, for several physical and strengthperformance measures, greater improvements were observed in the combined groups than in the diet-only groups (288-291, 293-297, 299).”
From ESPEN practical guideline: Clinical nutrition and hydration in geriatrics (2022) · cites this paper as [294]
The Results (Pain and Function; Mobility and HRQL, page not provided) show better function and a longer 6-minute walk distance in the diet-plus-exercise group than in the diet-only group. The paper describes strength training as part of the intervention but does not report a strength-performance improvement; its walk-speed comparison between those groups was not significant. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMany studies from the authors' group and others show improvements in muscle strength and function in older adults participating in lifestyle-based weight loss interventions, despite significant weight and lean mass loss.
“Likewise, many studies from our group (31, 32, 33), and others (34, 35), show improvements in muscle strength and function in older adults participating in lifestyle-based weight loss interventions, despite experiencing significant weight and LM loss (36, 37).”
Twelve RCTs compared the effects of a dietary weight loss intervention alone to a combination of the same dietary intervention with an exercise intervention in older persons.
“Twelve RCTs were identified that compared the effects of a dietary weight loss intervention alone to a combination of the same dietary intervention with an exercise intervention in older persons (288)(289)(290)(291)(292)(293)(294)(295)(296)(297)(298)(299).”
From ESPEN practical guideline: Clinical nutrition and hydration in geriatrics (2022) · cites this paper as [294]
Aerobic training has a strong association with weight loss.
“Aerobic exercise is also strongly linked to weight loss (Messier 2013)”
From Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews (2017) · cites this paper as Messier 2013
When older adults lose weight under supervision, their physical function and quality of life outcomes improve.
“When older adults lose weight under supervision, their physical function and QoL outcomes improve [48, 49].”
From Obesity pharmacotherapy in older adults: a narrative review of evidence (2025) · cites this paper as [48]
The vicious cycle of reduced physical activity and obesity is particularly pronounced in patients with knee OA, low back pain, and hip OA.
“This vicious cycle is particularly pronounced in patients with knee OA, low back pain, and hip OA.[ 6 ]”
From Exercise approaches in obese individuals with physical limitations (2026) · cites this paper as [6]
Among individuals with pain and movement restriction due to OA, reduced physical activity leads to obesity rates as high as 40 to 60%.
“Among individuals experiencing pain and movement restriction due to osteoarthritis (OA), reduced physical activity leads to obesity rates as high as 40 to 60%.”
From Exercise approaches in obese individuals with physical limitations (2026) · cites this paper as [6]
In the sarcopenic obesity phenotype, resistance exercises raise lower extremity muscle strength and reduce fall risk and frailty.
“In the sarcopenic obesity phenotype, resistance exercises raise lower extremity muscle strength and reduce fall risk and frailty.”
From Exercise approaches in obese individuals with physical limitations (2026) · cites this paper as [45]
In OA patients, resistance exercises increase strength by 15 to 40%.
“In OA patients, resistance exercises increase strength by 15 to 40%.”
From Exercise approaches in obese individuals with physical limitations (2026) · cites this paper as [45]
Adding resistance exercises to programs applying only aerobic exercises with an energy restricted diet reduces lean tissue loss, preserves fat mass reduction, and makes total weight loss more qualitative.
“In comparison to programs applying only aerobic exercises with an energy restricted diet, adding resistance exercises reduces lean tissue loss, preserves fat mass reduction, and makes total weight loss more qualitative.”
From Exercise approaches in obese individuals with physical limitations (2026) · cites this paper as [45]
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“[44,45] The recommended approach in sarcopenic obesity is low load (20 to 30% one-repetition maximum) and high repetition (15 to 20 repetitions).”
- Authors
- Messier, S. P., Mihalko, S. L., Legault, C., Miller, G. D., Nicklas, B. J., DeVita, P., Beavers, D. P., Hunter, D. J., Lyles, M. F., Eckstein, F., Williamson, J. D., Carr, J. J., Guermazi, A., & Loeser, R. F.
- Affiliations
- Wake Forest University Health Sciences (US)
- Wake Forest University (US)
- East Carolina University (US)
- The University of Sydney (AU)
- Paracelsus Medical University (AT)
- Boston University (US)
- Corresponding author
- Messier, Stephen P.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2013-09-25
- Volume
- 310
- Issue
- 12
- Pages
- 1263
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4450354
- OpenAlex
- W2103179033
- Cited by
- 873
- References
- 60
- Citations by year
- 2026: 83 · 2025: 79 · 2024: 75 · 2023: 51 · 2022: 80 · 2021: 82 · 2020: 78 · 2019: 60 · 2018: 74 · 2017: 51 · 2016: 53 · 2015: 56 · 2014: 44 · 2013: 5
- FWCI
- 42.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- National Institute on Aging (P30AG021332)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052528)
- National Center for Research Resources (M01RR000211)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Physical Sciences › Engineering › Biomedical Engineering › Lower Extremity Biomechanics and Pathologies
- Keywords
- knee osteoarthritis, obesity, overweight, weight loss, diet-induced weight loss, physical activity, knee joint loading, interleukin-6, inflammation, knee pain, knee function, health-related quality of life, older adults, home-based exercise, radiographic osteoarthritis
- MeSH terms
- Aged, Biomechanical Phenomena, Diet, Reducing, Exercise Therapy, Female, Humans, Inflammation, Male, Middle Aged, Obesity, Pain Measurement, Quality of Life, Biomarkers, Weight Loss, Interleukin-6, Body Mass Index, Single-Blind Method, Weight-Bearing, Treatment Outcome, Osteoarthritis, Knee, Overweight, Self Report
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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