CURRENT CONCEPTS IN OSTEOARTHRITIS
Márcia Uchôa de rezende1, GUstavo constantino de caMpos1, alexandre Felício pailo1
is not purely mechanical and / or aging, and clarification of
Osteoarthritis (OA), the most common form of joint disease, the inflammatory pathways involved led recently to the clinical affects mainly the hips, knees, hands and feet, leading to severe application of various drugs and other measures. This update disability and loss of quality of life, particularly in the elderly aims to expose the current concepts on the pathophysiology population. Its importance grows every year with the aging of and treatment of OA. the population, with a large increase in the elderly population compared to younger patients. The progressive understanding Keywords: Osteoarthritis. Arthritis. Osteoarthritis, knee. Osteoar-of the pathophysiology of OA, the perception that the process thritis, hip. Osteoarthritis/physiopathology.
Rezende MU, Campos GC, Pailo AF.Current concepts in osteoarthritis. Acta Ortop Bras. [online]. 2013;21(2):120-2. Available from URL: http://www.scielo.br/aob.
cimens and image studies, as well as due to the large amount
Osteoarthritis (OA) is the most common form of articular disease1 of activated biological processes in it. Key events that occur in and affects mainly hips, knees, hands, and feet. In USA, it the cartilage include metabolic unbalance and the emergence is estimated that 36.4% of the individuals aged 60 and over of degradation indicators, promoted by cytokine cascades, and present OA in the knees2 In Brazil, the population of individuals the production of inflammatory mediators.7 over 60 years old, today nearly 19 million, will increase in 2050 In patients with OA, the chondrocytes, as well as the synovial cells, to over 64 million.3 It is alarming data, considering disability, loss produce increased levels of inflammatory cytokines, as interleukin of quality of life and the costs to the health system generated 1β (IL-1β) and the alpha tumor necrosis factor (TNF-α), that, in turn, by this disease.4
decrease the collagen synthesis and increase catabolic mediators,
Until some decades ago, the treatment for OA was limited to such as metalloproteases (MMPs) and other inflammatory subs-the use of simple analgesic drugs, anti-inflammatories, physical tances as interleukin 8 (IL-8), interleukin 6 (IL-6), prostaglandin E2 procedures, infiltration with corticoids and, in unsusceptible (PGE2) and nitric oxide (NO).7 In addition, mechanical stress, as cases, surgical treatment. The progressive understanding of by static compression as by dynamic, increases the production physiopathology of OA, the perception that the process is not of NO by chondrocytes, as well as the expression of nitric oxide purely mechanical and/or due to aging, and the clarification of synthase (NOS).8the involved inflammatory paths lead to the clinical application Oxidizing agents, among them NO, promote apoptosis of chon-of several other drugs and procedures.5
drocytes, catabolic processes and degeneration of the matrix, therefore, causing two important pathogenic events characte-
ristic of the osteoarthritic chondrocytes - premature senescence and apoptosis. These events help build up the concept that OA
the importance of inflammation
is a disease of premature aging of the articulation.9
Risk factors such as gender, age, trauma, excessive use, gene-
Synovitis occurs even in the initial stages of OA and can be
tics, and obesity help to initiate the process of injury in different subclinical. Arthroscopic studies demonstrate alterations in the components of the articulation.6 It is already well established synovia in up to 50% of the patients with OA, many of which that the synovia, the bone and the cartilage are the three main did not present clinical signs of synovitis.10 Recent techniques tissues affected by the pathological mechanisms of the OA.6
using 3 Tesla nuclear magnetic resonance (NMR) demonstrated
The cartilage traditionally receives the main attention in OA stu-
that the synovial inflammation is more common than previously
dies, due to the massive destruction found in pathological spe-
estimated.6 Differently from Rheumatoid Arthritis (RA), the
Todos os autores declaram não haver nenhum potencial conflito de interesses referente a este artigo.
1. Institute of Orthopedics and Traumatology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – FMUSP, São Paulo, SP, Brazil.
Word developed at LIM 41 – Laboratory of Medical Investigation of the Muscle Skeletal System of the Department of Orthopedics and Traumatology, Faculdade de Medicina da
Universidade de São Paulo – FMUSP, São Paulo, SP, Brazil.
Mailing address: R. Ovídio Pires de Campos, 333 Cerqueira Cesar - São Paulo - SP, Brazil. CEP: 05403-010
Article received on 11/7/2012, and approved on 1/5/2013.
synovial inflammation in OA is usually found close to areas of disease; as well as the anti-inflammatory drugs, controversial pathologically damaged bone and cartilage. This hyper-reactive due to their side effects; and, finally, the drugs modifiers of the synovia can release proteinases and cytokines capable of osteoarthritis disease (DMOOAD), those capable of reversing, accelerating the articular damage.6
stabilizing or at least delaying the course of OA.5Among DMOOAD of oral use diacerein18, glicosamine19,
chondroitin20, the association of glucosamine with chondroitin21, the non-saponifiable extracts of soybean and avocado22 and
the growing importance of non-pharmacological handling
chloroquine are pointed out. Glucosamine and chondroitin
Over the years, various national and international guidelines were are, unquestionably, the most popular “chondroprotectors”.
developed in order to help the physicians, health professionals It has been recently discussed the relationship between
and patients in treatment selection for knee and hip OA treatment. the effectiveness of these substances and the type of used
In Brazil, the Brazilian Society of Rheumatology (SBR), through molecule, in addition to its isolated or associated use. Recent
Projeto Diretrizes, formulated in 2003 a consensus for OA metanalysis24, as well as a Cochrane systematic review19
treatment.11 More recently, the Osteoarthritis Research Society reported benefits with the use of sodium glucosamine sulfate
International (OARSI) published a recommendation guide12 with (Rotta type glucosamine) alone. A recent study also revealed
more rigid methodology, based on higher quality papers, which that the chondroitin, when combined, can compromise the
relies on regular reviews, as long as new clinical trials are being absorption of glucosamine.25 Meanwhile, there is not yet
consensus in the literature in this regard.
The better treatment for OA requires a combination of pharma-
Hyaluronic acid (HA) is an intra-articular DMOOAD, and its
cological and non- pharmacological procedures.12 All knee OA application is called visco-supplementation (VS).26 It has an
patients should have access to information and education con-
important modulating action, mainly through interaction with
cerning the objectives of the treatment and the importance of CD44 receptors present in type B “fibroblast-like” synoviocytes.27
changes in lifestyle, exercises, adequation of activities, weight Therefore, besides the mechanical effect of promoting better
reduction and other measures to diminish the impact on the da-
distribution of forces, reduce the pressure due to weight and
maged articulations. The initial focus should be on self-care and recovering the rheological properties of synovial fluid, hyaluronic
treatments directed to the patient instead of passive therapies acid also acts biochemically, reducing the gene expression
realized by health professionals.12 Emphasis should be given on of cytokines and enzymes associated from the OA.27 From
the incentive for adherence to the therapeutic not-pharmacolo-
the economic point of view there is an increasing number of
gical regimen. Patients should be encouraged to practice and studies showing that, if incorporated into the treatment of knee
maintain regular aerobic exercises, of muscular strengthening OA, VS can be cost-effective, including being able to delay the
and gain of movement amplitude. Patients with symptomatic completion of a total prosthetic knee.28
OA can benefit from physiotherapy referral for evaluation and Currently it is recommend the addition of 1 ml triamcinolone to
instruction to perform appropriate physical exercises to reduce visco-suplementation.29,30 The addition of corticosteroids makes
pain and increase the functional capacity.12
pain and function improvements occur earlier and in greater
The association between the Body Mass Index (BMI) and intensity, without compromising long term outcomes.30 It is also
knees OA is of great importance, since knees OA has a strong possible to maximize the benefits of VS through a prior joint
correlation with the highly inflammatory metabolic environment lavage. One should not wait for the failure of other treatment
found in obesity.13 Cytokines associated to the adipose tissue, options to consider VS, since it is known that patients who will
including adiponectine, leptine and resistine, can influence benefit most from this treatment are those whose disease is in
OA through the direct degradation of the articulation or by early stage (lower grade OA) and use the joints more actively.31
controlling local inflammatory processes. A recent systematic
review evaluated 36 studies on this correlation and found FINAL CONsIDErAtIONs
positive risk of BMI for OA development in all of them.14 Weight It is crucial to keep in mind that the treatment of OA is not scaled
loss reduces the pain and improves the physical function of the but multimodal. The patient should be educated about his disease
and encouraged to take an active behavior in his treatment. The
The use of canes and walkers is also recommended for sympto-
disease has no cure, but it can be controlled through diet, exercise,
matic OA of the knees, promoting improvement of the pain and use of orthosis, and medication administration. We must use the
lowering energy expenditure.15 The patients should be educa-
entire available therapeutic arsenal, and in case of failure, do
ted to correctly use a cane or crutch in the counter side hand, not hesitate to indicate surgical treatment. The joint replacement
walkers being preferable for patients with bilateral disease. The surgery still plays an important role in OA treatment. The total
use of orthosis or socks is also indicated to patients with axis hip replacement surgery was considered the surgery of the 20th
century by Lancet32, due to the strong positive impact that it can
Acupuncture is treatment modality with proved benefit in the bring to the patient’s quality of life .
relief of OA pain.16 Other body and mind therapies, such as
yoga, tai chi and qi gong also can be used in OA treatment, FUtUrE DIrECtING
with improvement evidences.17
The use of drugs is to complement non-pharmacological pro-
Comprehensive and individualized OA treatment
cedures. Among the available drugs, there are those essen-
Currently there is a major global effort to identify biomarkers
tially analgesic drugs, that do not interfere in the course of the of OA disease. These markers, found in blood, urine, or even
in the cell genome, would be able to produce information gene and the frazzled protein (FRZB).33 Just 10 years ago, the on the characteristics of the disease in a given individual, its cost to sequencing and individual’s genome was about $ 100 relationship with various risk factors, as well as control over million. Currently, this value is around ten thousand dollars, and the evolution of the disease, and why not, on the response soon, it is estimated that we can ask for a genome a study to intensities to the most various types of used treatments.
our patients as we ask, for example, for a MRI.
The most recent genetic studies, which present the most appro-
In the future, therefore, we will be able, through a blood test, or
priate approach for identifying susceptibility genes among the even a hair, to define the best treatment strategy, the best drugs complex genetic spectrum, have revealed some most convin-
and non-pharmacological procedures to be used by each of
cing signals, such as the 7q22 loci, which contains multiple po-
our patients, offering thus a comprehensive and individualized
tential genes such as the growth differentiation factor 5 (GDF5) treatment. Will this be true?
1. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al.
19. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, et
Estimates of the prevalence of arthritis and other rheumatic conditions in the
al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst
United States. Part II. Arthritis and rheumatism. 2008;58(1):26-35.
2. Dil on CF, Rasch EK, Gu Q, Hirsch R. Prevalence of knee osteoarthritis in
20. Hochberg MC, Zhan M, Langenberg P. The rate of decline of joint space width
the United States: arthritis data from the Third National Health and Nutrition
in patients with osteoarthritis of the knee: a systematic review and meta-
Examination Survey 1991-94. J Rheumatol. 2006;33(11):2271-9.
-analysis of randomized placebo-controlled trials of chondroitin sulfate. Curr
3. Projeção da população do Brasil por sexo e idade - 1980-2050 [database
on the Internet]. IBGE. 2008. Disponível em: http://www.ibge.gov.br/home/
21. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. Glu-
cosamine, chondroitin sulfate, and the two in combination for painful knee
4. Le TK, Montejano LB, Cao Z, Zhao Y, Ang D. Health care costs in US patients
osteoarthritis. N Engl J Med. 2006;354(8):795-808.
with and without a diagnosis of osteoarthritis. J Pain Res. 2012;5:23-30.
22. Christensen R, Bartels EM, Astrup A, Bliddal H. Symptomatic efficacy of avoca-
5. Rezende MU, Gobbi RG. Tratamento medicamentoso da osteoartrose do
do-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analy-
joelho. Rev Bras Ortop. 2009;44(1):14-9.
sis of randomized controlled trials. Osteoarthritis Cartilage. 2008;16(4):399-408.
6. Krasnokutsky S, Attur M, Palmer G, Samuels J, Abramson SB. Current concepts in
23. Vuolteenaho K, Kujala P, Moilanen T, Moilanen E. Aurothiomalate and hydro-
the pathogenesis of osteoarthritis. Osteoarthritis Cartilage. 2008;16(Suppl 3):S1-3.
xychloroquine inhibit nitric oxide production in chondrocytes and in human
7. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory
osteoarthritic cartilage. Scand J Rheumatol. 2005;34(6):475-9.
disease: potential implication for the selection of new therapeutic targets.
24. Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, et al.
The clinical effectiveness of glucosamine and chondroitin supplements in slowing
8. Fitzgerald JB, Jin M, Grodzinsky AJ. Shear and compression differentially regu-
or arresting progression of osteoarthritis of the knee: a systematic review and
late clusters of functionally related temporal transcription patterns in cartilage
economic evaluation. Health Technol Assess. 2009;13(52):1-148.
tissue. J Biol Chem. 2006;281(34):24095-103.
25. Jackson CG, Plaas AH, Sandy JD, Hua C, Kim-Rolands S, Barnhil JG, et al. The
9. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and
human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate
aging changes in the cartilage matrix. Osteoarthritis Cartilage. 2009;17(8):971-9.
taken separately or in combination. Osteoarthritis Cartilage.2010;18(3):297-302.
10. Ayral X, Dougados M, Listrat V, Bonvarlet JP, Simonnet J, Amor B. Arthroscopic eva-
26. Rezende MU, Campos GC. Viscosuplementação. Rev Bras Ortop.
luation of chondropathy in osteoarthritis of the knee. J Rheumatol. 1996;23(4):698-706.
11. Coimbra IB, Pastor EH, Greve JMD, Puccinelli MLC, Fuller R, Cavancanti FS,
et al. Osteoartrite (Artrose): Tratamento. Rev Bras Reumatol. 2004;44(6):450-3.
27. Wang CT, Lin YT, Chiang BL, Lin YH, Hou SM. High molecular weight hyalu-
12. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK,et
ronic acid down-regulates the gene expression of osteoarthritis-associated
al. OARSI recommendations for the management of hip and knee osteoar-
cytokines and enzymes in fibroblast-like synoviocytes from patients with early
thritis: part III: Changes in evidence following systematic cumulative upda-
osteoarthritis. Osteoarthritis Cartilage. 2006;14(12):1237-47.
te of research published through January 2009. Osteoarthritis Cartilage.
28. Torrance GW, Raynauld JP, Walker V, Goldsmith CH, Bellamy N, Band PA,et
al.; Canadian Knee OA Study Group. A prospective, randomized, pragmatic,
13. Sowers MR, Karvonen-Gutierrez CA. The evolving role of obesity in knee
health outcomes trial evaluating the incorporation of hylan G-F 20 into the
osteoarthritis. Curr Opin Rheumatol. 2010;22(5):533-7.
treatment paradigm for patients with knee osteoarthritis (Part 2 of 2): economic
14. Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteo-
results. Osteoarthritis Cartilage. 2002;10(7):518-27.
arthritis of the knee in older adults: a systematic review and meta-analysis.
29. Campos GC, Rezende MU, Pailo AF, Frucchi R, Pasqualin T. Estudo prospecti-
Osteoarthritis Cartilage. 2010;18(1):24-33.
vo e randomizado avaliando a adição de triancinolona à viscossuplementação
15. Jones A, Silva PG, Silva AC, Colucci M, Tuffanin A, Jardim JR, et al. Impact
of cane use on pain, function, general health and energy expenditure during
30. de Campos GC, Rezende MU, Pailo AF, Frucchi R, Camargo OP. Adding
gait in patients with knee osteoarthritis: a randomised controlled trial. Ann
triamcinolone improves viscosupplementation: a randomized clinical trial. Clin
Orthop Relat Res. 2013;471(2):613-20.
16. Manheimer E, Cheng K, Linde K, Lao L, Yoo J, Wieland S, et al. Acu-
31. Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic tra-
puncture for peripheral joint osteoarthritis. Cochrane Database Syst Rev.
jectory following intra-articular hyaluronic acid injection in knee osteoarthritis-
-meta-analysis. Osteoarthritis Cartilage. 2011;19(6):611-9.
17. Selfe TK, Innes KE. Mind-Body Therapies and Osteoarthritis of the Knee. Curr
32. Learmonth ID, Young C, Rorabeck C. The operation of the century: total hip
replacement. Lancet. 2007;370(9597):1508-19.
18. Fidelix TS, Soares BG, Trevisani VF. Diacerein for osteoarthritis. Cochrane
33. Meulenbelt I. Osteoarthritis year 2011 in review: genetics. Osteoarthritis Car-
Summer 2006 By Hedva Barenholtz Levy, PharmD, BCPS, Director, HbL PharmaConsulting What Are Laxatives? axatives are medications that are used to prevent or treat constipation. Consumers spendmore than $734 million dollars a year on laxatives. Constipation is estimated to occur inup to 40% of patient 65 years and older living in the community and is a common concernin older adult
Bird flu fear has gripped the globe, as the disease spreads. Public Health officials fear that a pandemic will occur if a recent strain of the virus, which has killed one-half of the humans it has infected, mutates into a form that can be transmitted between people. The virus has only infected humans who came into contact with contaminated birds. The strain (called H5N1) has kil