A brief discussion by Jonathan Krant, MD, GHLF and CreakyJoints Chief Medical Director

Dr. Krant is a board-certified rheumatologist with 20 years clinical experience running an academic service.


Osteoarthritis (OA, DJD) is a broadly-defined condition brought about by loss of articular cartilage and degradation of underlying bone. Typically non-inflammatory, OA is derived from the Greek ‘osteo’ (bone) and ‘itis’ (inflammation) – some feel that osteoarthrosis is a more accurate characterization of the disease state.

There is ‘nodal’ OA (typically Heberden’s and Bouchard’s nodes of the small joints of the hands), as well as less common ‘erosive’ OA, commonly thought to be inflammatory in nature. Risk factors for primary OA include genetics (with increased incidence among twin offspring of affected parents), mechanical stress (including misalignment), loss of cartilage and neurogenic causes of disease. Secondary OA is frequently seen in the context of rheumatoid arthritis, gout, diabetes, hypothyroidism and infection, amongst other causes.

Articular cartilage consists of a sponge-like material called proteoglycan, which both absorbs fluid and expels it under compressive force. Alterations in the biology of proteoglycan results in both higher fluid content and decreased compressibility. As the ability to resist load-bearing decreases, the impact of stress on underlying (subchondral) bone increases, with eventual cystic degeneration and spur formation.

This inevitable process of cartilage failure, joint space narrowing and bony erosion leads to pain with ambulation (especially involving the hips, knees and lumbar spine) and significant disability. The known clinical correlates of exercise intolerance, weight gain, immobility and mood alteration are well known to 27 million Americans (or more) whose OA accounts for 25% of physician visits and 50% of prescription NSAID use.

There is unequivocal evidence supporting the combination of weight loss, exercise, analgesic use (oral, injectable and topical) as well as assist devices (orthotics, canes) for patients with OA. Joint injection with ‘viscoelastic’ hyaluronic acid derivatives provides temporary benefit for some, while oral NSAID use (ibuprofen, Naprosyn and the like) are beneficial, yet not without significant risk for GI bleeding and impaired kidney function when taken continuously for 6 weeks or longer. Tylenol may confer less risk of adverse events, and has good analgesic properties when taken in full therapeutic doses.

Topical NSAIDs (diclofenac drops or gel rubbed into the joint capsule for example) has proven benefit, and there is limited clinical trial-based evidence supporting specific dietary supplements for OA disease management.

One of the great mysteries for physicians managing patients with OA is the apparent discrepancy between advanced radiographic appearance of disease and its clinical features. Despite virtual ‘bone on bone’ anatomy, some patients continue to run, bike, hike and compete in racquet sports while others, with less radiographically-apparent disease burden, are dramatically more affected. Comorbid conditions, drug tolerance (especially with the opioid analgesics), reluctance to embrace behavioral change and other management issues make OA a challenging condition, for both patient and physician.

Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is the prototypic autoimmune disease, characterized by the five cardinal signs of inflammation (warmth, redness, swelling, tenderness and diminished function).

Although joints and organ systems are frequently affected, the fatigue, episodic fever and malaise which accompany early disease are crippling features with significant impact on patients with newly-diagnosed RA. Usually occurring in people ranging in age from their mid-twenties to mid-fifties (with a female predominance of 2:1), RA occurs in 1-2% of the world’s population with occasional variations in prevalence.

This brief discussion will address the genetics of disease susceptibility, clinical features and therapeutic options for patients with RA, including the controversial areas of disease recognition and strategies utilized to treat disease with variations in clinical activity. Controversies surrounding access and distribution are also discussed.

RA is thought to result from a combination of genetic-specified risk factors and environmental exposures which place individuals at risk. The HLA-DR4 locus is an established genetic susceptibility marker, with IgM rheumatoid factor (RF) a commonly-encountered plasma biomarker of disease. The interleukins, especially IL-1 and IL-6 are known cytokines produced by activated cells implicated in disease activity, and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count and fibrinogen are non-specific markers of inflammation, often tracked in patients both before and after therapeutic intervention as surrogate markers of clinical response. A variety of infections have been implicated as possible precipitants of disease in genetically-susceptible individuals, including viral and mycoplasma upper respiratory infections. Patients with early disease may report the explosive onset of joint swelling plus fever, fatigue and generalized malaise. By contrast, some patients with RA never develop such ‘full-blown’ features and present with rather indolent symptoms (aching, tenderness, soreness) which tend to persist at a low-level of disease activity.

Therapeutic strategies are a topic of debate in the rheumatologic community. For patients with explosive disease onset, moderate doses of prednisone or prednisolone are frequently prescribed, along with NSAIDs for an interval of four to six weeks. A lack of response or persistence of clinical features can lead to a DMARD prescription (methotrexate, hydroxychloroquine, azulfadine) in addition to DMARDs, NSAIDs plus/minus steroids. Patients may be treated in this manner for up to 12 weeks prior to consideration of biologic therapy.

Biologics targeting selective elements of the inflammatory pathway, may be added by the 12th week of ongoing disease activity. There are a variety of molecules available for the treating rheumatologist, including both sq and infusion-based regimens of TNF antagonists, IL-1 and IL-6 inhibitors and, if evidence of disease activity persists, selective B-cell inhibitor therapy available via infusion. Oral therapy targeting the janus kinase pathway has recently become available, and the potential benefits of developing targeted, effective therapies to be used in combination with background DMARD (with limited adverse events) has become the holy grail of drug development in this domain.

The downside of parenteral therapy for rheumatoid arthritis (and its cousins, the inflammatory spondyloarthropathies) are legion. Injection site reactions with erythrocyte sedimentation rate (ESR) subcutaneous therapy, low-grade infection, potential drug interactions and malignancy are areas attracting active surveillance by patients and physicians alike. The ideal timing for drug administration, the value of persistence with one agent (as compared with switching within class or to another class of drug) is another area of intense discussion.

Legislative efforts to make drug available for the indigent (these molecules may cost upwards of $30,000 dollars per annum), and changing algorithms among the indemnity plans for access to drug continue to evolve. There are significant barriers to access across continents, based on variations in budget and risk tolerance among health agencies abroad. Finally, the requirements for safe shipping, including maintenance of the cold chain and gentle handling of fragile proteins are also significant impediments to drug distribution.

The most important element in the dialogue involving RA is early disease recognition. Understanding the protean manifestations of disease, both explosive-onset and indolent phenotypes as well as differing approaches to disease management constitute the art and the science of managing RA.

  • Was This Helpful?