Current management of Osteoarthritis

Osteoarthritis (OA) is a chronic degenerative disorder of multifactorial
etiology characterized by loss of articular cartilage and periarticular bone
remodelling. OA causes joint pain, typically worse with weight-bearing and activity
as well as can manifest with stiffness after inactivity. It can present as localized,
generalized or as erosive osteoarthritis. Primary osteoarthritis is mostly related
to aging, whereas, secondary osteoarthritis is caused by another disease or
condition. X-rays, arthrocentesis and arthroscopy remain the main diagnostic
tools. Blood tests are performed to exclude diseases that can cause secondary
osteoarthritis. The treatment of osteoarthritis include non-pharmacological
management, pharmacological treatment in the form ofdrugs which can
modify symptoms, symptomatic slow acting drugs for OA or structure modifying
OA drugs depending upon the clinical requirement of the patient. Patients with
persistent pain and progressive limitation of daily activities despite medical
management may be the candidates for surgery.

OSTEOARTHRITIS

INTRODUCTION

 Osteoarthritis (OA) is a chronic degenerative disorder of multifactorial
etiology characterized by loss of articular cartilage, hypertrophy of bone at
the margins, subchondral sclerosis and range of biochemical and morphological
alterations of the synovial membrane and joint capsule. Pathological changes
in the late stage of OA include softening, ulceration and focal disintegration
of the articular cartilage; synovial inflammation also may occur. Typical clinical
symptoms are pain, particularly after prolonged activity and weight bearing;
whereas stiffness is experienced after inactivity.¹ It is probably
not a single disease but represents the final end result of various disorders
as joint failure. It is also known as degenerative arthritis, which commonly
affects the hands, feet, spine, and large weight-bearing joints, such as the
hips and knees. It can present as localized, generalized or as erosive osteoarthritis.
Most cases of osteoarthritis have no known cause and are referred to as primary
osteoarthritis. Primary osteoarthritis is mostly related to aging. Secondary
osteoarthritis is caused by another disease or condition.¹ Osteoarthritis
(OA) is the second most common rheumatological problem and is most frequent
joint disease encountered in the clinical practice.² This is the
most common cause of locomotor disability in the elderly³. Gastrointestinal
toxicity is present in 50% of NSAIDs users and 5.4% develop a more serious event
requiring hospitalisation due to its frequent use. This may have a significant
impact on overall cost of therapy in patients of OA in spite the fact that they
are not very costly.^{4, 5} Hence, OA represents a major cause of morbidity
and disability, as well as a significant economic burden on patients and health
care resources.The review focuses on latest modalities of treatment in OA.

MANAGEMENT OF OSTEOARTHRITIS

Goals of managing osteoarthritis include controlling pain, maintaining and improving range of movement and stability of affected joints and limiting functional impairment .⁶

NON-PHARMACOLOGICAL MANAGEMENT

Education, behavioral intervention, weight loss, lower extremity strengthening exercise for 20-30 minutes per day, quadriceps strengthening, gait training, active range of motion of hip, knee and ankle, instructions in use of cane, graded elastic band use and pool therapy are modestly effective in reducing pain and disability.⁷ Mechanical aids in the form of shock-absorbing footwear with good mediolateral support, adequate arch support and calcaneal cushion are also helpful. Lateral heel wedges may reduce pain related to osteoarthritis of medial tibiofemoral compartment⁸ and applying adhesive tapes to patella can provide relief in patellofemoral osteoarthritis.⁹

PHARMACOLOGICAL MANAGEMENT

I .Symptom modifying drugs:

Acetaminophen is often effective in osteoarthritis, associated with fewer adverse reactions than NSAIDs and is recommended as initial therapy for osteoarthritis in addition to non-pharmacological interventions.¹⁰ Salicylates and traditional NSAIDs are considered only for patients who do not obtain adequate pain relief with paracetamol.¹¹ COX-2 inhibitors can be considered for use because of better gastrointestinal tolerability. Ceecoxib, etoricoxib in the dose of 60 mg/day and valdecoxib 10mg/day are as  efficacious as non-selective NSAIDs in pain relief^12,13. However recent studies are challenging the safety of COX-2 inhibitors. Misoprostol as co- therapy in selective patients requiring chronic NSAIDs treatment may help to prevent gastric ulcers.¹⁴

Opioids (codeine) and paracetamol in combination provide better analgesia than paracetamol alone.¹⁵ Treatment with tramadol results in statistically significant and clinically important and sustained improvement in pain, stiffness, physical function, global status and sleep in patients with chronic pain.¹⁶ Tramadol 37.5 mg / Acetaminophen 325 mg combination is also effective and safe for treatment of osteoarthritis pain.¹⁷ Topical analgesics(0.025% capsaicin cream ¹⁸and other local NSAIDs¹) have been considered appropriate as an adjunct to simple analgesia, monotherapy for a single symptomatic joint or for patients who cannot tolerate systemic therapy. The mechanism of action of capsaicin is thought to be through selective stimulation of unmyelinated type C afferent neurons, causing the release of substance P. Such a release reversibly depletes the store of substance P, a neurotransmitter of peripheral pain sensation.¹

In general, intra-articular corticosteroid injections are believed to be most effective in patients with evidence of inflammation, effusion, or both. Because of concerns over possible deleterious effects, usually no more than four corticosteroid injections per year are given in a particular joint.¹ Intra-articular glucocorticoid injection, afford  moderate and short-lived reduction in pain.¹⁹ Triamcolone hexacetonide (TH) suspension is a relatively long acting corticosteroid commonly used for IA injection.²⁰ Patients presenting with significant inflammation with demonstrable CPPD crystals in joint have better symptomatic relief with colchicines.

II. Symptomatic slow acting drugs for OA (SYSADOA)

Hyaluronic acid (HA) is a linear polysaccharide composed of repeating disaccharide units of N-acetyl glucosamine and D-glucoronic acid. Two of these agents-hyalgan and synvis- are approved for viscosupplementation in the United States for use in OA of the knee. Multiple injections spaced 1 week apart provide reduction in pain and beneficial effects last for upto 6 months, much longer than as compared to intraarticular steroids. Synvisc requires three injections per course of treatment, whereas hyalgan requires five. They are often mentioned as potential structure modifying agents but are presently considered as symptom-modifying drugs only. There is an evidence for an anti-inflammatory effect, a short-term lubricant effect, an analgesic effect by directly buffering of synovial nerve endings and a stimulating effect on synovial lining cells leading to production of normal hyaluronic acid.¹ The therapeutic benefit of its multiple intraarticular injections may be comparable to that of NSAIDs.²¹ Hylan GF-20 (synvisc) is a high molecular weight cross-linked derivative of hyaluronan that has elastoviscous properties similar to healthy synovial fluid. Its efficacy for treatment of osteoarthritis knee pain, with low incidence of local adverse effects, has been demonstrated in difrent clinical trials.²² Hyaluronic acid products are also being actively investigated in shoulder joint OA, periarthritis and adhesive capsulitis.¹

Nutriceuticals: Pair of nutritional supplements, namely glucosamine sulphate and chondroitin sulphate have received significant attention. Glucosamine sulphate is a derivative of the naturally occurring amino monosaccharide glucosamine, a constituent of glycosaminoglycan chain in aggrecans and other proteoglycans found in synovial fluid and cartilage of joints. It is a substrate for synthesis of mucopolysaccharides and there is latency of 4-8 weeks before therapeutic effect emerges.²³ Two randomized, controlled, double blind trials in Belgium²⁴and Czech Republic²⁵ suggested that this drug ( 1.5 g daily) has a substantial symptom and structure modifying effect in patients with mild to moderate osteoarthritis of knee.

Chondroitin sulphate similarly provides additional substrates for formation of healthy joint matrix. Evidence also supports oral administration of chondroitin sulphate to slowly reduce symptoms and to reduce need for NSAIDs .²⁶ It ameliorates the symptoms of osteoarthritis, though this effect only occurs after longer period of time.²⁷  Chondroitin has been found to be effective on Lequesne index,and visual analog scale. Mobility and responding status is also excellent (800 mg/day).²⁸ Combined use of glucosamine sulphate and chondroitin sulphate in treatment of degenerative joint disease has become an extremely popular supplementation protocol in OA.²⁹

Other drugs¹ in this category are ginger extract which actually contain salicylate and has inhibitory effect on COX and lipooxygenase. Similarly oral preparations of avocado and soy unsaponifiables (ASU) have been shown in vitro to inhibit IL-6, IL-8, MMPs and stimulate collagen synthesis. Cat’s claw and shark cartilage treatment leads to an improvement in symptoms of OA, as they also contain chondroitin sulphate. Most recently another compound (S- Adenosyl methionine), an oxygen radical scavenger has been shown to reduce pain in OA but still larger trials are awaited. 

III. Structure modifying OA drugs (SMOADS) /chondroprotective¹

Tetracyclines are inhibitors of tissue metalloproteinases. This could be due to their ability to chelate calcium and zinc ions. Minocycline and doxycycline have been shown to inhibit articular cartilage collagenase activity, prevent proteoglycan cell loss, cell death and deposition of type X-collagen matrix. Glycosaminoglycan polysulfuric acid (GAGPS), known as arteparon, work through reducing the collagenase activity and has shown promising results. Similarly other agents like glycosaminoglycan peptide complex (GC-P) known as rumalon has shown to increase the levels of tissue inhibitors of metalloproteinase, while pentosan polysulfate (cartrofen) inhibits granulocyte elastase. However, larger clinical trials have yet to prove their structure modifying activity. Diacrein and its active metabolite rhein has the capability to inhibit IL-I beta in human synovium. It has improved pain score in patients of OA as well as it has been proposed as structure modifying drug for OA. Moreover disease modification potential of agents like glucosamine, hyaluronan, growth factors and cytokine manipulation, gene therapy as well as chondrocyte and stem cell transplant need further evaluation.

Other: Various other therapies include transcutaneous nerve stimulation, local massage, thermal modalities, acupuncture, amitriptyline, pain management counseling and support groups. Assistive devices in knee osteoarthritis, physical therapy in form of knee sleeves, cane or walker and occupational therapy are modalities which can be very useful¹.

Surgery: Patients with persistent pain and progressive limitation of daily activities despite medical management may be referred for surgical intervention to an orthopedic surgeon.³⁰

In conclusion, the treatment of OA includes a variety of possible
non-pharmacological, pharmacological and surgical interventions. Treatment
should be tailored to individual and will consist of a combination of available
modalities.

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Vishal  Tandon* , Annil Mahajan.

Dr Vishal Tandon received doctorate in Pharmacology from Nagpur University,
Maharashtra (India). He authored and/or coauthored over 40 publications in many
national and international journals. His research interests include herbal drug
screening, especially working on plant vitex negundo. He is currently working
as Senior demonstrator, Post graduate department of pharmacology and therapeutics,
GMC, Jammu (J&K)-India. His current job responsibilities include teaching
UG/PG classes as well as supervising research.

Currently he is Editorial Secretary for JK-SCIENCE,
Journal of Medical Education &Research. This journal is indexed in Excerpta
Medica/EMBASE, Ulrich periodical Dictionary& Indian Science Abstract and
also he is Secretary to Indian Rheumatology Association-J&K CHAPTER. He
is life member of Indian
Pharmacological society , Association of Physiologist and Pharmacologist
of India and Indian
Rheumatology Association .

*Author for Correspondense:

Dr Vishal. R. Tandon (MD) (Senior Demonstrator) , Post Graduate Department
of Pharmacology & Therapeutics GMC, Jammu (J&K) India - 180001. E-mail:
dr_vishaltandon@yahoo.com Phone: 9419195126.

Dr Annil Mahajan is working presently as Assistant
professor, Post Graduate epartment of Obstetrics & Gynaecology, Govt Medical
College, Jammu (J&K) India – 180001.He is Editor-in-chief , JK-SCIENCE,
Journal of Medical Education &Research. Dr.Annil Mahajan bears the foloowing
important postions.He is member National editorial board, journal of indian
rheumatology association. He is member National Advisory board, Journal of the
association of physicians of india and Journal Indian Acedemy of clinical Medicine.
He is also member National executive committee, Indian rheumatology association
as well as he remained member All India Advisory board (2004), for JIMA .He
also bears the post of President, Indian Rheumatology association (Jammu Kashmir
chapter) and Joint Secretary,Indian menopause society, Jammu Chapter.