obesità, infiammazione e malattie reumatologiche: è ... · obesità e malattie reumatiche:...

Obesità, infiammazione e malattie reumatologiche:è possibile un approccio terapeutico integrato?

Prof. Fausto [email protected]

Clinica Reumatologica – Early Arthritis Clinic - Dipartimento di Scienze Cliniche e Molecolari -

Università Politecnica delle Marche, Ancona

Both overweight

and obesity are

associated with

the incidence of

multiple

comorbidities

Including

rheumatic

disorders

Obesità e malattie reumatiche: elementi fisiopatologici e potenziali biomarkers

Obesità e rischio di insorgenza della malattia reumatica: profilo epidemiologico e predittori

Obesità ed impatto sull’attività e severità dellamalattia reumatica

Obesità e risposta al trattamento con farmacibiologici

Obesità ed approccio terapeutico integrato

OBESITA’ & MALATTIE REUMATICHE

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Obesity rarely exists on its own; instead,

it tends to coexist with other

comorbidities, including metabolic,

cardiovascular, and rheumatic and

musculoskeletal diseases (RMDs). In the

case of RMDs, evidence is rapidly

accumulating on common mechanistic

pathways implicated in the inflammatory

states seen between RMDs and obesity

The chronic state of low-grade

inflammation present in the obese

condition and the multiple

pleiotropic effects of adipokines

on the immune system has been

implicated in the pathogenesis of

several inflammatory conditions

including rheumatic autoimmune

and inflammatory diseases

Evaluating the effects of weight

loss on the

inflammatory/autoimmune

disease course appears to be

crucial in terms of potential

clinical and also

pharmacoeconomics

perspectives.

Potential

mechanisms

explaining the

link between

obesity and

inflammatory

arthritis.

The white adipose tissue (WAT) is considered a

major endocrine organ through the capability of

secreting adipocytokines. In obese individuals,

WAT hosts many immune cell populations

interacting with adipocytes. Obesity is a risk

factor for both rheumatoid arthritis (RA) and

osteoarthritis (OA), and it is likely that some

adipocytokines are involved in the pathogenesis

of these two diseases. These adipocytokines

may be involved in the increased cardiovascular

risk observed in RA and OA patients.

Adipokine serum

levels in autoimmune

rheumatic diseases.

Adipokines, mainly

produced by adipose

tissue, have mixed pro-

and anti-inflammatory

properties.

Adiposity triggers metabolicinflammation, in which various

adipokines released from adipose tissuesinduce pro-inflammatory cytokines in

the synovium and chondrocytes, ultimately leading to cartilage matrix

damage and subchondral bone remodelling

Mechanisms linking

abdominal obesity

and metabolic

syndrome via

inflammatory

mediators

Mechanisms relating obesity to OA

Higher levels of adiposityare accompanied by

metainflammation, with production of adipokines

and proinflammatorycytokines. The combinedeffect of adipocytokines

and increased loading can facilitate the pathogenesis

of OA, affecting bone, cartilage and synovial

tissue.

In all populations, the prevalence of osteoarthritis (OA) rises with age, but the hypothesis of mismatch predicts thatprevalence at any given age is higher in modern environments because of high levels of obesity , chronic metaflammationand physical inactivity, and diets of processed foods that are rich in sugar and saturated fats and low in fibre

Model of osteoarthritis as a mismatch disease

Obesity and OA: a vicious cycle

Obesity can affect the pathogenesis of OA through biomechanical effects as well as via

increased metainflammation. Increasedobesity is associated with higher levels of

joint loading and reduced levels of physicalactivity, which in turn reduces muscle

strength. Combined, these effects can resultin the structural changes of OA. Structural

disease results in pain, which presents a barrier to physical activity, further reducing

energy expenditure and resulting in reducedmuscle mass and increased fat mass.







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This national study has

demonstrated that the odds of

osteoarthritis (OA) was up to 7

times higher for obese

individuals, compared with

those classified as

underweight/normal weight. OA was up to 7 times higher

for obese individuals

Forest plot for the

aggregate risk of

knee osteoarthritis

for obesity versus

normal weight.

Meta-analysis of studies for osteoarthritis.

The incidence of knee, hip, and

hand OA increased with

increasing BMI, with a greater

increase for knee OA

Forest plot for the

aggregate risk of

knee osteoarthritis

with the increase of

a 5 kg/m2 of body

mass index.

In comparison with subjects of normal weight, without Heberden’s nodes, and with no history of kneeinjury, people with a combination of obesity, definite Heberden's nodesand previous knee injury had a relative risk of 78 (95% CI 17 ± 354).

The incidence of knee, hip,

and hand OA increased with

increasing BMI, with a greater

increase for knee OA

The incidence of knee, hip,

and hand OA increased with

increasing BMI, with a

greater increase for knee OA

The overall and dose-

response meta-analysis

showed that increased BMI

was associated with an

increased risk for rheumatoid

arthritis, which might present

a prevention strategy for the

prevention or control of

rheumatoid arthritis.

Sixteen studies that included a total of

406,584 participants were included in

the meta-analysis

This general population study

suggests that obesity is

associated with an increased risk

of incident PsA and supports the

importance of weight reduction

among psoriasis patients who

often suffer the metabolic

syndrome and obesity.

Two large prospective studies

that suggest obesity is a risk

factor for PsA.

These studies offer valuable new

information on the link between obesity

and PsA and provide a potential

opportunity to reduce the occurrence of

PsA by encouraging a reduction in

weight, a modifiable risk factor.

Understanding and

implementation of

these measures could

reduce the severe

comorbidity associated

with psoriatic disease.

Fibromyalgia is a chronic disorder of

uncertain etiology, characterized by

widespread pain, muscle tenderness, and

decreased pain threshold to pressure and

other stimuli.

Epidemiological data show that

fibromyalgia patients have higher

prevalence of obesity (40%) and

overweight (30%) in multiple studies

compared with healthy patients

Among mechanisms proposed,

there are the following: impaired

physical activity, cognitive and

sleep disturbances, psychiatric

comorbidity and depression,

dysfunction of thyroid

gland, dysfunction of the GH/IGF-1

axis, impairment of the

endogenous opioid system.







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Pain and functional disability

are more severe in obese and

overweight knee OA patients

compared to those with

normal BMI, and obesity is an

independent predictor of

functional disability.

Obesity is an independent risk factor for functional disability in patients with knee OA.

Obesity combined with lowmuscle strength increasesthe risk of decline in walking speed and developing mobilitydisability, especially amongpersons <80 years old.

Work disability due to osteoarthritis accordingto body mass index

Musculoskeletal disorders are the most frequent cause of work disability in this cohort: the riskof disability due to osteoarthritisincreased with BMI

Relative risk ratiosdemonstrating the cross-sectionalrelationshipbetween obesity and total hip and kneearthroplasty.

Obesity had a negative influenceon outcome aftertotal kneearthroplasty.

Presurgical obesity is

associated with worse clinical

outcomes of hip or knee

arthroplasty in terms of pain,

disability and complications in

patients with osteoarthritis.

This meta-analysis of prospective cohort studies demonstrates that obesity negatively influences the overall complication rate, dislocation rate, functional outcome and operative time of primary total hip arthroplasty.

Overall result demonstrated that obese patient appeared to undergo a higher deep infection rate than non-obese patients.

Obesity was associated with

worse RA disease outcomes

and a higher prevalence of

comorbidities. Body

measurements are

recommended to improve

prediction of the disease

course.

it has been described that abdominal obesity is

associated with high disease activity, high

disability, physical inactivity and poor mental

health in a cohort of RA patients.

Evidence clarified that adipose tissue is a dynamic endocrine

organ that releases several bioactive substances including some

pro-inflammatory cytokines like TNF-α and IL-6, and specific

cytokines, termed adipokines, that may have a key role in RA

pathogenesis.

BMI is linked to both axial

and peripheral new bone

formation and entheseal

inflammation by imaging,

as supported by the limited

number of studies in the

literature

The association between obesity

and new bone formation highlights

the importance of biomechanical

factors in patients with SpA.

Biomechanical factors can be

considered the trigger of an

inflammatory process, so the

response of healing at these sites

can be associated with

new bone formation

Obesity was related significantly to

greater pain sensitivity to TP

palpation particularly in the lower

body areas, reduced physical

strength and lower-body flexibility,

shorter sleep duration, and greater

restlessness during sleep.

Obesity is a common co-

morbidity that may complicate

the clinical picture of FMS.

We found that obesity is

common in FMS. Approximately

a half of our patients were obese

and additional 30% were

overweight







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The results of our meta-analysis

suggest that obesity and overweight

reduce the chances to achieve

minimal disease activity (MDA) in

patients with rheumatic diseases

receiving treatment with traditional

or biologic disease-modifying

antirheumatic drugs.

Forest plot of minimal disease activity achievement in obese patients versus normal-

weight patients with rheumatic diseases

Obese patients were

shown to have a poorer

response rate to

treatment in all outcome

measures in comparison

to the overweight and the

normal-weight RA

patients.

Obesity represents a risk

factor for a poor

remission rate in patients

with longstanding RA

treated with

anti-TNF agents.

Percentage of Disease

Activity Score in 28 joints

(DAS28) remission in

obese and nonobese

rheumatoid arthritis

patients treated with

adalimumab (ADA),

etanercept (ETA), and

infliximab (IFX). None of

the obese patients

responded to IFX.

…..RA and PsApatients with obesityhave a poor responseto biological anti-TNF drugs….

Data suggest that being female,

overweight and mostly obese is

associated with a lower rate of

success in obtaining response

status in axial SpA patients treated

with anti-TNF drugs. Body weight

could represent a modifiable factor

to reach the best outcome in axial

SpA patients treated with TNF

blockers

Obesity is associated with significantly lower response rates to TNFi in patients with axSpA.

While being overweight decreased

the odds of achieving an ASAS40

response upon TNF inhibition by

about 30%, the odds were decreased

by 70% in obese patients.







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Obesity is a major risk factor for OA, and weight loss is effectiveat reducing the risk of OA, butadherence to interventions is

poor and should be addressed by personalized strategies

A conceptual model of OA

Obesity is a risk factor for manyconditions, including knee OA. The benefit of modifying thisrisk factor may cause significantrisk reduction of knee OA in the general population.

The meta-analysis

indicated that knee OA

risk increased almost

exponentially according

with the increase of body

mass index. Knee OA

prevention will benefit

from weight control

Meta regression analysis

indicated that physical

disability of patients

with knee OA and

overweight diminished

after a moderate

weight reduction regime.

Pain

Disability

The main factors associated with

onset of knee pain were being

overweight (pooled OR 1.98, 95%

confidence intervals (CI) 1.57 e

2.20), obesity (pooled OR 2.66

95% CI 2.15 - 3.28), female gender

(pooled OR 1.68, 95% CI 1.37 e

2.07), previous knee injury

(pooled OR 2.83, 95% CI 1.91 e

4.19).

Obesity in particular needs to

be a major target for prevention

of development of knee pain.

Overweight and obese patients areat >40% and 100% increased risk of kneereplacement surgery, respectively, compared to patients with normal weight.

Weight reduction strategies couldpotentially reduce the need for kneereplacement surgery by 31% amongpatients with knee OA.

The results should

encourage clinicians to

consider exercise therapy

as a treatment option for

patients with knee

osteoarthritis, even in the

presence of severe

comorbidity.

For knee OA, primary prevention includes the prevention of knee injury. Secondary preventionincludes dietary intervention and exercise in individualswho are overweight, have impaired muscle function or prior joint injury, whereas tertiary prevention involvesearly treatment of OA to prevent progression of the disease. The OA continuum

Overweight patients were 25% less

likely, and obese patients were 47% less

likely, to achieve sREM in the first 3 years,

despite similar initial disease-modifying

antirheumatic drug treatment and

subsequent biologic use. This is the largest

study demonstrating the negative impact of

excess weight on RA disease activity and

supports a call to action to better identify

and address this risk in RA patients

Weight may be a

potentially modifiable risk

factor to consider in

overweight and obese

early RA patients who

demonstrate an

inadequate response to

therapy.

Short-term weight loss

treatment was associated with

significant positive effects on

disease activity in joints,

entheses and skin in patients

with PsA and obesity.

The study supports the

hypothesis of obesity as a

promotor of disease activity in

PsA.

The percentage of patients reaching American College of Rheumatology (ACR) 20, ACR 50 and ACR 70

response criteria, Psoriatic Arthritis Response Criteria (PsARC) and Minimal Disease Activity (MDA). BL,

baseline; M6, 6 months visit

Patients in the higher BMI categories

were less likely to achieve sustained

MDA compared those in the lowest

BMI category (overweight: OR 0.66

p=0.003; obese: OR 0.53 p<0.0001)

after adjusting for potential

confounding variables.

Overweight and obese patients

with PsA are less likely to achieve

sustained MDA compared to

those of normal weight.

Weight loss may improve the long-

term outcome and overall health of

the patients and increase their

chances of achieving disease

remission

Evidence strongly suggests that

comorbid obesity is common in chronic

pain conditions, and pain complaints are

common in obese individuals.

Based upon the existing research, we

present several potential mechanisms that

may link the two phenomena, including

mechanical/structural factors, chemical

mediators, depression, sleep, and lifestyle

Weight loss/exercise

therapy for obese pain

patients appears to be an

important aspect of

overall pain rehabilitation

Classifica degli sport più

praticati al mare:

1) Corsa

2) Beach volley

3) Racchettoni

4) Nuoto

5) Apnea per tenere in dentro la pancia

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