RESUMEN
OBJECTIVE: Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (3-year efficacy) PA program a cost-effective component of long-term OA care. METHOD: Using a validated computer microsimulation (Osteoarthritis Policy Model), we examined the long-term clinical (e.g., comorbidities averted), quality of life (QoL), and economic impacts of a 3-year PA program, based upon the SPARKS (Studying Physical Activity Rewards after Knee Surgery) Trial, for inactive knee OA patients. We determined the cost, efficacy, and impact of PA on QoL and medical costs that would make a PA program a cost-effective addition to OA care. RESULTS: Among the 14 million with knee OA in the US, >4 million are inactive. Participation of 10% in the modeled PA program could save 200 cases of cardiovascular disease, 400 cases of diabetes, and 6,800 quality-adjusted life-years (QALYs). The program had an incremental cost-effectiveness ratio (ICER) of $16,100/QALY. Tripling PA program cost ($860/year) raised the ICER to $108,300/QALY; varying QoL benefits from PA yielded ICERs of $8,800/QALY-$99,900/QALY; varying background cost savings from PA did not qualitatively impact ICERs. Offering the PA program to any adults with knee OA (not only inactive) yielded $31,000/QALY. CONCLUSION: A PA program with 3-year efficacy in the knee OA population carried favorable long-term clinical and economic benefits. These results offer justification for policymakers and payers considering a PA intervention incorporated into knee OA care.
Asunto(s)
Análisis Costo-Beneficio , Ejercicio Físico , Osteoartritis de la Rodilla/economía , Osteoartritis de la Rodilla/terapia , Calidad de Vida , Humanos , Modelos Teóricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time. DESIGN: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance. RESULTS: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (ß: -24.59 µm, 95%CI: -41.86, -7.33) and mean (ß: -19.08 µm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups. CONCLUSIONS: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit. CLINICAL TRIAL REGISTRATION: NCT00381290.
Asunto(s)
Dieta Reductora , Ejercicio Físico , Meniscos Tibiales/diagnóstico por imagen , Obesidad/terapia , Osteoartritis de la Rodilla/diagnóstico por imagen , Programas de Reducción de Peso , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Meniscos Tibiales/patología , Persona de Mediana Edad , Obesidad/complicaciones , Tamaño de los Órganos , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/fisiopatología , Sobrepeso/complicaciones , Sobrepeso/terapia , Método Simple Ciego , Pérdida de PesoRESUMEN
OBJECTIVE: Diet restriction and exercise form key treatments for osteoarthritis (OA) related symptoms in overweight and obese individuals. Although both interventions are known to influence systemic low-grade inflammation, which is related to pain levels and functional limitations, little is known about the potential changes in systemic inflammation as a working mechanism of diet restriction and exercise in knee OA. DESIGN: Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used. Through causal mediation analyses, the proportion of the effect of a 18 months diet and exercise intervention explained by the 18 months change in interleukin (IL)-6, TNF-α, soluble IL-6 receptor, soluble IL-1 receptor, CRP, and BMI were assessed, using self-reported pain and function as outcomes. RESULTS: The change in inflammatory factors accounted for 15% of the total effect on pain and was totally independent of the change in BMI. The change in inflammatory factors accounted for 29% of the effect on function, with the change in BMI adding only 4% to the total mediated effect. CONCLUSIONS: The change in inflammatory factors after the diet and exercise intervention was a 'medium' size mediator of the effect on pain and a 'strong' mediator for the effect on function in overweight and obese individuals with knee OA. The change in BMI added minimally to the mediated effect on function. These results highlight the relevance of changes in systemic inflammation as drivers for clinically relevant effects after diet and exercise in overweight and obese individuals with knee OA.
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Citocinas/sangre , Dieta Reductora , Ejercicio Físico , Osteoartritis de la Rodilla/terapia , Anciano , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Sobrepeso/terapia , Dimensión del Dolor , Evaluación del Resultado de la Atención al PacienteRESUMEN
OBJECTIVE: The cost-effectiveness of the recently-introduced generic celecoxib in knee OA has not been examined. METHOD: We used the Osteoarthritis Policy (OAPol) Model, a validated computer simulation of knee OA, to evaluate long-term clinical outcomes, costs, and cost-effectiveness of generic celecoxib in persons with knee OA. We examined eight treatment strategies consisting of generic celecoxib, over-the-counter (OTC) naproxen, or prescription naproxen, with or without prescription or OTC proton-pump-inhibitors (PPIs) to reduce gastrointestinal (GI) toxicity. In the base case, we assumed that annual cost was $130 for OTC naproxen, $360 for prescription naproxen, and $880 for generic celecoxib. We considered a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) and discounted costs and benefits at 3% annually. In sensitivity analyses we varied celecoxib toxicity, discontinuation, cost, and pain level. RESULTS: In the base case analysis of the high pain cohort (WOMAC 50), celecoxib had an incremental cost-effectiveness ratio (ICER) of $284,630/QALY compared with OTC naproxen. Only under highly favorable cost, toxicity, and discontinuation assumptions (e.g., annual cost below $360, combined with a reduction in the cardiovascular (CV) event rates below baseline values) was celecoxib likely to be cost-effective. Celecoxib might also be cost-effective at an annual cost of $600 if CV toxicity were eliminated completely. In subjects with moderate pain (WOMAC 30), at the base case CV event rate of 0.2%, generic celecoxib was only cost-effective at the lowest plausible cost ($190). CONCLUSION: In knee OA patients with no comorbidities, generic celecoxib is not cost-effective at its current price.
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Celecoxib/uso terapéutico , Simulación por Computador , Costos de los Medicamentos , Medicamentos Genéricos/administración & dosificación , Osteoartritis de la Rodilla/tratamiento farmacológico , Anciano , Celecoxib/economía , Análisis Costo-Beneficio , Medicamentos Genéricos/economía , Femenino , Humanos , Masculino , Osteoartritis de la Rodilla/economía , Resultado del TratamientoRESUMEN
OBJECTIVE: Quadriceps muscle weakness is common in knee osteoarthritis (OA). While pain, disuse, and atrophy are commonly cited causes for muscle weakness in OA, emerging evidence suggests changes in muscle quality also occur. Alterations in muscle quality are not well understood, but likely include both cellular and morphologic adaptions. The purpose of this study was to conduct the first cellular-level analysis of the vastus lateralis in adults with moderate knee OA. METHODS: Vastus lateralis biopsies were obtained from 24 subjects with moderate knee OA and 15 healthy controls. Quadriceps strength, muscle fiber cross sectional area (CSA), fiber type distribution, extracellular matrix (ECM) content, satellite cell abundance, and profibrotic gene expression were assessed. RESULTS: Relative to controls, quadriceps strength was significantly lower in OA subjects (OA 62.23, 50.67-73.8 Nm vs 91.46, 75.91-107.0 Nm, P = 0.003) despite no difference in fiber CSA. OA subjects had significantly fewer Type I fibers (OA 41.51, 35.56-47.47% vs 53.07, 44.86-61.29%, P = 0.022) and more hybrid IIa/x fibers (OA 24.61, 20.61-28.61% vs 16.4, 11.60-21.20%, P = 0.009). Significantly greater ECM content, lower satellite cell density, and higher profibrotic gene expression was observed with OA, and muscle collagen content was inversely correlated to strength and satellite cell (SC) density. CONCLUSION: Lower quadriceps function with moderate OA may not result from fiber size impairments, but is associated with ECM expansion. Impaired satellite cell density, high profibrotic gene expression, and a slow-to-fast fiber type transition may contribute to reduced muscle quality in OA. These findings can help guide therapeutic interventions to enhance muscle function with OA.
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Matriz Extracelular/metabolismo , Fuerza Muscular/fisiología , Debilidad Muscular/etiología , Osteoartritis de la Rodilla/diagnóstico , Músculo Cuádriceps/patología , Células Satélite del Músculo Esquelético/patología , Anciano , Biopsia , Estudios Transversales , Matriz Extracelular/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/metabolismo , Debilidad Muscular/fisiopatología , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/metabolismo , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/fisiopatología , ARN/genética , Células Satélite del Músculo Esquelético/metabolismoRESUMEN
OBJECTIVE: To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA). DESIGN: Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA) trial randomized to either an 18 month exercise control group (E), weight loss diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6) were quantitated using ELISAs. Radiographic progression was defined as a decrease in joint space width of ≥0.7 mm. Statistical modeling of group means and associations used mixed models adjusted for visit, baseline body mass index (BMI), gender, and baseline values of the outcome. RESULTS: Compared to the E control group, C1M was significantly lower in the D and D + E groups at both 6 and 18 months while C3M was significantly lower in D and D + E at 6 months and in D + E at 18 months. C2M did not change in any group. Using data from all groups, change in C1M (P < 0.0001), C3M (P < 0.0001), as well as CRPM (P = 0.0004) from baseline to 18 months was positively associated with change in weight. No marker was associated with change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or radiographic progression. C3M (P = 0.008) and CRPM (P = 0.028) were positively associated with change in WOMAC function. Change in IL-6 was positively associated with change in C1M, C3M, and CRPM. CONCLUSION: Overweight and obese adults with knee OA who lost weight from diet and diet plus exercise reduced serum markers of interstitial matrix turnover and inflammation but not type II collagen degradation.
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Dieta Reductora/métodos , Ejercicio Físico , Obesidad/terapia , Osteoartritis de la Rodilla/metabolismo , Pérdida de Peso , Anciano , Proteína C-Reactiva/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Colágeno Tipo III/metabolismo , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/metabolismo , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/fisiopatología , Sobrepeso/epidemiología , Sobrepeso/metabolismo , Sobrepeso/terapia , Radiografía , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the gait of adults with unilateral and bilateral symptomatic and radiographic knee osteoarthritis (OA) to determine whether these subgroups can be treated similarly in the clinic and when recruiting for randomized clinical trials, and to use these data to generate future hypotheses regarding gait in these subsets of knee OA patients. METHODS: Cross-sectional investigation of patients with unilateral and bilateral knee OA on gait mechanics using 136 older adults (age ≥55 yrs; 27 kg m(-2) ≥ BMI ≤ 41 kg m(-2); 82% female) with radiographic knee OA. Comparisons were made between the most affected side of the bilateral group (Bi) and the affected side of the unilateral group (Uni), and between symmetry indices of each group. RESULTS: There were no significant differences in any temporal, kinematic, or kinetic measures between the Uni and Bi cohorts. Comparison of symmetry indices between groups also revealed no significant differences. CONCLUSION: The similarity in lower extremity mechanics between unilateral and bilateral knee OA patients is sufficiently robust to consider both subsets as a single cohort. We hypothesize that biomechanical adaptations to knee OA are at least partially systemic in origin and not based solely on the physiological characteristics of an affected knee joint.
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Marcha/fisiología , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Anciano , Articulación del Tobillo/fisiopatología , Fenómenos Biomecánicos , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Dimensión del Dolor/métodos , Radiografía/métodos , Rango del Movimiento Articular/fisiología , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Metabolic factors may contribute to osteoarthritis (OA). This study employed metabolomics analyses to determine if differences in metabolite profiles could distinguish people with knee OA who exhibited radiographic progression. METHODS: Urine samples obtained at baseline and 18 months from overweight and obese adults in the Intensive Diet and Exercise for Arthritis (IDEA) trial were selected from two subgroups (n = 22 each) for metabolomics analysis: a group that exhibited radiographic progression (≥0.7 mm decrease in joint space width, JSW) and an age, gender, and body mass index (BMI) matched group who did not progress (≤0.35 mm decrease in JSW). Multivariate analysis methods, including orthogonal partial least square discriminate analysis, were used to identify metabolite profiles that separated progressors and non-progressors. Plasma levels of IL-6 and C-reactive protein (CRP) were evaluated as inflammatory markers. RESULTS: Multivariate analysis of the binned metabolomics data distinguished progressors from non-progressors. Library matching revealed that glycolate, hippurate, and trigonelline were among the important metabolites for distinguishing progressors from non-progressors at baseline whereas alanine, N,N-dimethylglycine, glycolate, hippurate, histidine, and trigonelline, were among the metabolites that were important for the discrimination at 18 months. In non-progressors, IL-6 decreased from baseline to 18 months while IL-6 was unchanged in progressors; the change over time in IL-6 was significantly different between groups. CONCLUSION: These findings support a role for metabolic factors in the progression of knee OA and suggest that measurement of metabolites could be useful to predict progression. Further investigation in a larger sample that would include targeted investigation of specific metabolites is warranted.
Asunto(s)
Osteoartritis de la Rodilla , Adulto , Progresión de la Enfermedad , Humanos , Articulación de la Rodilla , Obesidad , SobrepesoRESUMEN
The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA.
Asunto(s)
Ensayos Clínicos como Asunto/normas , Dietoterapia/normas , Terapia por Ejercicio/normas , Estilo de Vida , Osteoartritis/dietoterapia , Osteoartritis/rehabilitación , Guías de Práctica Clínica como Asunto , HumanosRESUMEN
PURPOSE: Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA). METHODS: Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27-41 kg m(-2)) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender. RESULTS: Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D -0.07 (SE 0.22) mm, D + E -0.27 (SE 0.22) mm and E -0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D -0.10(0.05) mm, D + E -0.13(0.04) mm and E -0.05(0.04) mm (P = 0.42). CONCLUSION: Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.
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Dieta Reductora , Terapia por Ejercicio/métodos , Osteoartritis de la Rodilla/terapia , Anciano , Índice de Masa Corporal , Terapia Combinada , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/etiología , Radiografía , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del Tratamiento , Pérdida de PesoRESUMEN
OBJECTIVE: To describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss. DESIGN: Data come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models. RESULTS: Intentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (ß = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (ß = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss. CONCLUSIONS: Achievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.
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Proteína C-Reactiva/análisis , Interleucina-6/sangre , Osteoartritis de la Rodilla/sangre , Sobrepeso/sangre , Anciano , Dieta Reductora , Ejercicio Físico , Femenino , Humanos , Masculino , Obesidad/sangre , Obesidad/complicaciones , Osteoartritis de la Rodilla/complicaciones , Sobrepeso/complicaciones , Método Simple Ciego , Pérdida de PesoRESUMEN
OBJECTIVE: To determine the influences of frontal plane knee alignment and obesity on knee joint loads in older, overweight and obese adults with knee osteoarthritis (OA). METHODS: Cross-sectional investigation of alignment and obesity on knee joint loads using community dwelling older adults (age ≥ 55 years; 27 kg m(-2) ≥ body mass or body mass index (BMI) ≤ 41 kg m(-2); 69% female) with radiographic knee OA that were a subset of participants (157 out of 454) enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) clinical trial. RESULTS: A higher BMI was associated with greater (P = 0.0006) peak knee compressive forces [overweight, 2411 N (2182, 2639), class 1 obesity, 2772 N (2602, 2943), class 2+ obesity, 2993 N (2796, 3190)] and greater (P = 0.004) shear forces [overweight, 369 N (322, 415), class 1 obesity, 418 N (384, 453), class 2+ obesity, 472 N (432, 513)], independent of alignment, and varus alignment was associated (P < 0.0001) with greater peak external knee adduction moments, independent of BMI [valgus, 18.7 Nm (15.1, 22.4), neutral, 27.7 Nm (24.0, 31.4), varus, 37.0 Nm (34.4, 39.7)]. CONCLUSION: BMI and alignment were associated with different joint loading measures; alignment was more closely associated with the asymmetry or imbalance of loads across the medial and lateral knee compartments as reflected by the frontal plane external adduction moment, while BMI was associated with the magnitude of total tibiofemoral force. These data may be useful in selecting treatment options for knee OA patients (e.g., diet to reduce compressive loads or bracing to change alignment).
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Desviación Ósea/fisiopatología , Marcha/fisiología , Articulación de la Rodilla/fisiopatología , Obesidad/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Soporte de Peso/fisiología , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Fenómenos Biomecánicos/fisiología , Índice de Masa Corporal , Desviación Ósea/complicaciones , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicacionesRESUMEN
OBJECTIVE: To determine the effects of dietary-induced weight loss (D) and weight loss plus exercise (D + E) compared to exercise alone (E) on bone mineral density (BMD) in older adults with knee osteoarthritis (OA). DESIGN: Data come from 284 older (66.0 ± 6.2 years), overweight/obese (body mass index (BMI) 33.4 ± 3.7 kg/m2), adults with knee OA enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) study. Participants were randomized to 18 months of walking and strength training (E; n = 95), dietary-induced weight loss targeting 10% of baseline weight (D; n = 88) or a combination of the two (D + E; n = 101). Body weight and composition (DXA), regional BMD, were obtained at baseline and 18 months. RESULTS: E, D, and D + E groups lost 1.3 ± 4.5 kg, 9.1 ± 8.6 kg and 10.4 ± 8.0 kg, respectively (P < 0.01). Significant treatment effects were observed for BMD in both hip and femoral neck regions, with the D and D + E groups showing similar relative losses compared to E (both P < 0.01). Despite reduced BMD, fewer overall participants had T-scores indicative of osteoporosis after intervention (9 at 18 months vs 10 at baseline). Within the D and D + E groups, changes in hip and femoral neck, but not spine, BMD correlated positively with changes in body weight (r = 0.21 and 0.54 respectively, both P ≤ 0.01). CONCLUSIONS: Weight loss via an intensive dietary intervention, with or without exercise, results in bone loss at the hip and femoral neck in overweight and obese, older adults with OA. Although the exercise intervention did not attenuate weight loss-associated reductions in BMD, classification of osteoporosis and osteopenia remained unchanged. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.
Asunto(s)
Densidad Ósea/fisiología , Obesidad/dietoterapia , Obesidad/rehabilitación , Osteoartritis de la Rodilla/terapia , Pérdida de Peso/fisiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Índice de Masa Corporal , Terapia Combinada , Intervalos de Confianza , Dieta Reductora/métodos , Terapia por Ejercicio/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad/complicaciones , Osteoartritis de la Rodilla/complicaciones , Sobrepeso/complicaciones , Sobrepeso/dietoterapia , Sobrepeso/rehabilitación , Valores de Referencia , Medición de Riesgo , Método Simple Ciego , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). METHODS: Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into 'Unloaders' (participants that reduced joint loads) and 'Loaders' (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. RESULTS: 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: -2.4 KOOS points [95% CI -6.8:1.9]) and cartilage loss (group difference: -0.06 BLOKS points [95% CI -0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. CONCLUSION: For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. CLINICALTRIALSGOV: NCT00655941.
Asunto(s)
Marcha/fisiología , Articulación de la Rodilla/fisiopatología , Obesidad/terapia , Osteoartritis de la Rodilla/rehabilitación , Programas de Reducción de Peso , Anciano , Fenómenos Biomecánicos , Cartílago Articular/patología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/fisiopatología , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/patología , Estudios Prospectivos , Resultado del Tratamiento , Caminata , Pérdida de Peso/fisiología , Soporte de PesoRESUMEN
BACKGROUND: Prior work shows caloric restriction (CR) can improve physical function among older adults living with obesity. However, the contribution of starting weight and inflammatory burden to CR-associated functional improvements is unclear. The primary purpose of this study was to determine if CR-associated gait speed change varied by body mass index (BMI) and plasma interleukin 6 (IL-6) at baseline and secondarily to determine the contribution of BMI change and IL-6 change to gait speed change. DESIGN, SETTING, PARTICIPANTS: Data from eight randomized control trials were pooled, with 1184 participants randomized to CR (n=661) and No CR (n=523) conditions. All studies assessed outcomes before and five or six months after assignment to CR or No CR. MEASUREMENTS: BMI and IL-6 were assessed at baseline using standard procedures. Gait speed was assessed with the six-minute walk test or 400m walk test. Baseline BMI/IL-6 subgroups were constructed using BMI≥35 kg/m2 and IL-6>2.5 pg/mL thresholds. Participants with BMI≥35 kg/m2 were grouped into class 2+ obesity and BMI<35 kg/m2 into class 1- obesity; IL-6>2.5 pg/mL were grouped into high IL-6, and <2.5 pg/mL as low IL-6 (class 2+ obesity/high IL-6: n=288, class 2+ obesity/low IL-6: n=143, class 1- obesity/high IL-6: n=354, or class 1- obesity/low IL-6: n=399). All analyses used adjusted general linear models. RESULTS: Gait speed significantly improved with CR versus non-CR [mean difference: +0.02 m/s (95% CI: 0.01, 0.04)]. CR assignment significantly interacted with BMI/IL-6 subgroup membership (p=0.03). Greatest gait speed improvement was observed in the class 2+ obesity/high IL-6 subgroup [+0.07 m/s (0.03, 0.10)]. No other subgroups observed significant gait speed change. For each unit decrease in BMI, gait speed change increased by +0.02 m/s (p<0.001; R2=0.26), while log IL-6 change did not significantly affect gait speed change [+0.01 m/s (p=0.20)]. CONCLUSIONS: Only the class 2+ obesity/high IL-6 subgroup significantly improved gait speed in response to CR. Improvement in gait speed in this subgroup was driven by a larger decrease in BMI, but not IL-6, in response to CR. Individuals with class 2+ obesity and high IL-6 are most likely to show improved gait speed in response to CR, with improvement predominantly driven by reductions in BMI.
Asunto(s)
Interleucina-6 , Velocidad al Caminar , Humanos , Anciano , Índice de Masa Corporal , Restricción Calórica , ObesidadRESUMEN
OBJECTIVE: To determine the effect of an intensive weight loss program on knee joint loads during walking in obese patients with knee osteoarthritis (OA). METHODS: Participants included 157 obese knee OA patients that underwent a 16-week dietary intervention. Three-dimensional gait analyses were performed before and after the intervention at the participants' freely chosen walking speed. Knee joint compression forces, axial impulses, knee flexion angle and frontal and sagittal plane knee moments were calculated to determine the biomechanical effects of the weight loss. RESULTS: 157 subjects (89% of the initial cohort) completed the 16-week intervention. The average weight loss of 13.7 kg (P<.0001) corresponded to 13.5% of the baseline body weight. The weight loss resulted in a 7% reduction in knee joint loading, a 13% lower axial impulse, and a 12% reduction in the internal knee abductor moment (KAM). There were no clear effects on sagittal plane knee moments or peak knee flexion angle. Linear regression analyses adjusted for changes in walking speed showed that for every 1 kg in weight loss, the peak knee load was reduced by 2.2 kg. Thus, every kilo reduction in body weight was related to more than twice the reduction in peak knee force at a given walking speed. CONCLUSION: Weight loss is an excellent short-term investment in terms of joint loading for patients with combined obesity and knee OA. The effects of sustained weight loss on disease progression and symptoms in relation to biomechanical factors remain to be shown.
Asunto(s)
Dieta Reductora , Articulación de la Rodilla/fisiopatología , Obesidad/dietoterapia , Osteoartritis de la Rodilla/dietoterapia , Pérdida de Peso , Anciano , Estudios de Cohortes , Femenino , Marcha , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/fisiopatología , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/fisiopatología , Radiografía , Caminata , Pérdida de Peso/fisiología , Soporte de PesoRESUMEN
OBJECTIVE: The aim of this study was to examine the effects of high weight loss on knee joint loads during walking in participants with knee osteoarthritis (OA). DESIGN: Data were obtained from a subset of participants enrolled in the Arthritis, Diet, and Activity Promotion Trial (ADAPT). Complete baseline and 18-month follow-up data were obtained on 76 sedentary, overweight or obese older adults with radiographic knee OA. Three-dimensional gait analysis was used to calculate knee joint forces and moments. The cohort was divided into high (>5%), low (<5%), and no (0% or gain) weight loss groups. RESULTS: From baseline body weight, the high weight loss group lost an average of 10.2%, the low weight loss group lost an average of 2.7%, and the no weight loss group gained 1.5%. Adjusted 18-month outcome data revealed lower maximum knee compressive forces with greater weight loss (P=0.05). The difference in compressive forces between the high weight loss and no weight loss groups was due primarily to lower hamstring forces (P=0.04). Quadriceps forces were similar between the groups at 18-month follow-up. There was no difference between the groups in 18-month joint space width or Kellgren-Lawrence scores. CONCLUSIONS: These results suggest that a 10% weight loss in an overweight and obese osteoarthritic population elicits positive changes in the mechanical pathway to knee OA by having lower knee joint compressive loads during walking compared to low and no weight loss groups. The difference in compressive forces was due, in large part, to reductions in hamstring co-contraction during the initial portion of the stance phase.
Asunto(s)
Dietoterapia , Terapia por Ejercicio , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Sobrepeso/terapia , Pérdida de Peso/fisiología , Adulto , Peso Corporal , Estudios de Cohortes , Femenino , Marcha , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , Sobrepeso/fisiopatología , Radiografía , Estrés Mecánico , Caminata , Soporte de PesoRESUMEN
The design and execution of prevention trials for OA have methodological issues that are distinct from trials designed to impact prevalent disease. Disease definitions and their precise and sensitive measurement, identification of high-risk populations, the nature of the intervention (pharmaceutical, nutraceutical, behavioral) and its potential pleiotropic impacts on other organ systems are critical to consider. Because prevention trials may be prolonged, close attention to concomitant life changes and co-morbidities, adherence and participant retention in the trial is of primary importance, as is recognition of the potential for "preventive misconception" and "behavioral disinhibition" to affect the ability of the trial to show an effect of the intervention under study. None of these potential pitfalls precludes a successful and scientifically rigorous process and outcome. As technology improves the means to measure and predict the OA process and its clinical consequences, it will be increasingly possible to screen individuals for high-risk phenotypes, combining clinical factors with information from imaging, genetic, metabolic and other biomarkers and to impact this high-risk condition to avoid or delay OA both structurally and symptomatically.