Etiology and pathogenesis: The osteoarthritis (OA) is the leading cause of physical disability, increased health care utilization and costs, as well as a substantially impaired quality of life, in our modern, industrialized society. More than 56 millions Americans suffer from this condition today, and this is a number much larger than all the patients with diabetes, cancer, HIV/AIDS and hypertension taken together. Moreover, the impact of this arthritic condition is expected to grow with both the population increase and its aging during the coming decades. OA was thought in the past to be a normal consequence of aging, therefore considered a “degenerative joint disease”. Now, however, we realize that OA results from a multi-factorial pathogenesis, affecting the joint integrity and including aging itself, trauma or other mechanical forces, a certain genetic predisposition, a local inflammation associated to the late stages of cartilage degeneration, as well as a complex cellular and biochemical process. Despite an extensive prevalence and a very heterogenous pathogenesis, only in part understood today, the progression of OA remains beyond our explanation, due in part to multiple factors including our inability to detect the early phase of the disease, as well as the lack of appropriate procedures to replace the damaged cartilage. The cartilage injury appears during the early stages, however a complete cartilage loss occurs in the late stages of the disease and is the key element of the joint impairment with its subsequent necessity of joint replacement. If, we will be able to re-grow a normal healthy cartilage in an advanced osteoarthritic joint, the chances of a prolonged life and functionality of this joint may be expected, and eventually OA may be cured.

Clinical presentation

     Osteoarthritis has traditionally been subdivided by etiology into either idiopathic or secondary forms:

  • Idiopathic osteoarthritis: Idiopathic OA can be categorized into localized or generalized forms of the disease. Localized OA most commonly affects the hands, feet, knee, hip, and spine. Other joints are less commonly involved; these include the shoulder, temporo-mandibular, sacroiliac, ankle, and wrist joints. Generalized OA consists in the involvement of three or more joint sites.
  • Secondary osteoarthritis: Specific conditions may cause or enhance the risk of developing osteoarthritis. These include: trauma, congenital or developmental disorders, calcium pyrophosphate dihydrate deposition disease (CPPD or pseudogout), uric acid deposition (gout), other bone and joint disorders including osteonecrosis, or inflammatory rheumatoid arthritis, gouty arthritis, septic arthritis, sarcoidosis or Paget disease of bone. Although not uniformly true, these forms of OA are more likely to be present in an atypical fashion, such as an acute pain, or with unusual patterns of joint involvement, like the “lock-in” or joint instability, as well as the “ground-glass” sensation also named crepitus. Independent of underlying etiology, OA can also be classified by anatomic involvement. These include the site of chief joint involvement and the presence of single or multiple joint involvement.


     Drug therapy is a key component of OA treatment. Many different types of drugs are available, however, very few of them are able to stop the progression of the disease.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve the pain by reducing the inflammatory component of OA. Many of the nonprescription products that are available for treating arthritis pain are NSAIDs. These drugs are often recommended before analgesics for people who have osteoarthritis and evidence of inflammation. They are also recommended for some patients with noninflammatory OA who do not get adequate pain relief with simple analgesics. Ibuprofen, Naproxen, Ketoprofen, Etodolac, Sulindac, Diclofenac, Piroxicam, Meloxicam or Celebrex are some of the most frequently used medications of this class.
  • Analgesics relieve the pain but do not have any effect on inflammation. These drugs are often recommended only when osteoarthritis pain does not respond to nonpharmacologic measures. Drugs in this class include acetaminophen (Tylenol) and opioid (narcotic) analgesics. The pain of sudden, severe arthritis exacerbations may require treatment with narcotic analgesics, however it should be a short term treatment because the narcotics can be very addictive and very often require to escalate the dose for the same effect of pain relief.
  • Two types of joint injections are used for patients with OA: steroid injections and injections of viscous liquid polymers known as hyaluronates.
  • Steroid injections: the long acting steroid cortisole (Depo-Medrol, Aristopan) has a strong anti-inflammatory action and can very effectively suppress the inflammation and relieve symptoms when injected into the arthritic joints. Joint injections have few side effects, but some people experience a short flare of arthritis symptoms after a steroid injection. There is also a very small risk of joint infection.
  • Viscous fluid injections are designed to restore the normal joint fluid which contains a large amount of hyaluronates, the molecules from the cartilage biochemical structure. The synthetic substitutes may be injected into the knees of people with osteoarthritis. Modest pain relief has been achieved with a series of injections, approximately equivalent to that obtained by use of an NSAID. However, this relief may last for several months. Joint inflammation has occasionally occurred after this type of injection.
  • Colchicine - This drug is often recommended for people with inflammatory osteoarthritis that does not improve with nonpharmacologic therapies and NSAIDs. Inflammatory OA has been very often linked to the presence of calcium, urig acid or apatite crystals in the joints. A clinician may recommend continuous use of colchicine for patients who have frequent flares of osteoarthritis that is resistant to other treatments. However, people who have kidney or liver disease may need a reduced daily dose or may be unable to use it at all because of an increased risk of side effects when damaged organs can not clear colchicine from the body.
  • Hydroxychloroquine - (Plaquenil) has immune system modulating effects that reduce the inflammation of arthritis in some people. This drug may be recommended for patients with severe inflammatory OA and to those who have bone damage related to osteoarthritis, the most advanced form of OA also named “inflammatory erosive OA”. An eye exam yearly is recommended for patients using this drug for more than 6 months to avoid any type of toxic effects on the retina, the inner layer of the eye.
  • Methotrexate – on a weekly dose of 10 to 20 mg/week, as it is used in the treatment of rheumatoid arthritis, may be also very useful in stopping the bone erosions frequently found in cystic erosive inflammatory OA. Frequently the erosive OA may be associated with seronegative rheumatoid arthritis, when this medication is highly recommended. Methotrexate treatment has to be associated with a daily dose of 1 mg folic acid for internal organ protection and has to be monitored with lab work every two to three months.
  • Nonpharmacologic therapies for OA - include exercise programs, weight loss, patient education, and physical therapy including a very useful aquatic therapy program. The nonpharmacologic interventions, other than surgical approaches, are generally recommended before the start of medication. Especially weight loss and moderate stretching/relaxing exercises with the recondition of the muscles and tendons strength may be very useful from the beginning of the therapy. Acupuncture and alternative and complementary therapies are also useful in different clinical conditions and for a limited group of patients.
  • Dietary supplements - like Glucosamine, MSM or Chondroitin sulfates, are frequently addressed in the approaches of OA treatment. However, besides the alleviation of the pain, there are no other clear cut evidence that this medication can reduce or stop the progression of the disease. The rebuilding of the cartilage integrity using these components is also controversial and without enough clinical or experimental evidence.
  • Orthopedic surgery is the last resort in the treatment of OA. Arthroscopic surgery was not proven to be superior to the medical treatment unless a structural damage like ligament or meniscus tear is present. Total joint replacement may be a successful option if used in the right patient. The judgments and recommendation for this radical procedure belongs to specialized orthopedic surgeons who use their clinical skills and experience to predict the full success of the procedure. The age, the body weight, the patient’s mobility and compliance, as well as the type of joint and the amount of joint damage have to be taken into consideration when such a complex surgical procedure is decided.

Additional information