Arthritis – Osteoarthritis

Understanding Osteoarthritis

Normal Joint Anatomy and Function

The bones of the human skeletal system are connected by a complex series of joints, which connect two or more bones and allow for a wide variety of movements that would otherwise be impossible (Briant 2008).

In order to facilitate smooth joint movement, the surfaces of joints are lined by a low-friction, load-distributing, wear-resistant tissue called articular cartilage, which is composed of 65 to 80 percent water, collagen (fibrous proteins), proteoglycans, and chondrocytes (cells that produce cartilage) (Pearle 2005). In adults, damaged cartilage has a very limited capacity for self-healing due to blood supply limitations, and the relatively poor capacity of resident chondrocytes to migrate and proliferate (Henrotin 2009).

Joints can be classified as synovial, fibrous, or combination joints, based on the presence or absence of a synovial membrane and the amount of motion that occurs in the joint.

Normal synovial joints allow a significant amount of motion the articular surface. These joints are composed of the following:

• Articular cartilage
• Subchondral bone
• Synovial membrane
• Synovial fluid
• Joint capsule

Normal articular surface of synovial joints consists of articular cartilage surrounded by proteoglycans and collagen. The cartilage protects the underlying subchondral bone by distributing large loads, maintaining low contact stresses, and reducing friction.

Synovial fluid supplies nutrients to the articular cartilage; it also absorbs shock from slow movements, as well as the elasticity required to absorb shock from rapid movements.

Osteoarthritis Onset and Progression

Osteoarthritis (OA) can occur in any freely moving joint in the body, but it most commonly affects load- and stress-bearing joints like the knees, lumbar spine, and hips (Lawrence 2008).

At the onset of OA, where cartilage cells depart from their normal pattern of growth and differentiation, the outermost layer of articular cartilage begins to soften as its protein structure degrades. As OA progresses, this loss of protein content becomes more rapid, affecting deeper and deeper layers of cartilage (Pearle 2005). Eventually, the entire protective layer of cartilage is destroyed as the chondrocytes become completely overwhelmed and unable to reverse the tissue damage.

Because cartilage does not contain free nerve endings, joint destruction is typically not associated with pain until it is considerably advanced. This is a major reason why OA tends to be diagnosed so late in the disease process (Bijlsma 2011; Felson 2005).

With a majority of the protective cartilage now gone, the raw surfaces of the bones become exposed to gradual bone-on-bone erosion. This process inevitably leads to the destruction/deformation of nearly all the joint structures involved in movement, and is often accompanied by chronic inflammation in and around the joint space (i.e., synovial membrane) (Pearle 2005).

In many cases, the bone destruction caused by OA is followed by “remodeling”, which is characterized by bone spurs that grow along the joint margins. Although these bony outgrowths are believed to stabilize the injured joint by increasing bone surface area, they are also a significant source of pain, as joint movement causes them to rub against adjacent bones, nerves, and/or soft tissue (Mayo Clinic 2009; Pearle 2005). The intensity of symptoms can vary significantly, ranging from mild to severe (Strand 2011).

The pain caused by OA is typically worsened upon physical activity. As the disease progresses, however, patients may begin to report pain even when resting. Complaints of stiffness tend to occur more frequently in the morning, and often resolve shortly after awakening. However, any period of prolonged inactivity can cause this stiffness, which is sometimes referred to as “inactivity gelling” (Kalunian 2012b).

In cases of advanced OA, patients often report both physical and psychosocial disability. In fact, along with cardiovascular disease, OA causes more disability than any medical condition among the elderly (Hunter 2009).

Arthritis – Osteoarthritis

The Cause & Risk Factors

Osteoarthritis (OA) arises as a result of a complex interplay of factors such as aging, mechanical forces, joint integrity, local inflammation, genetics, and congenital abnormalities (Kalunian 2012a; Bijlsma 2011).

Risk factors for osteoarthritis include (Seed 2011; Busija 2010):

• Advanced age
• Female gender
• Obesity (see below)
• History of physical labor
• High-impact sports
• Joint trauma
• Family history

Obesity and Osteoarthritis

Because obesity increases the load and stress on many joints, it appears to be one of the most influential risk factors contributing to the development or advancement of osteoarthritis (OA) (Busija 2010). However, studies of obese patients have identified a high prevalence of OA in non-weight bearing areas (e.g., finger joints) as well (Rai 2011).

Data reveal that fat tissue is a major source of catabolic and pro-inflammatory mediators (i.e., cytokines, chemokines, and adipokines), which are implicated in the process of OA (Rai 2011). In addition, obese patients tend to experience insulin resistance and increased glucose load, which may also contribute to the chronic inflammation and cartilage degradation of OA (Sowers 2010).

Since OA has been linked not only to obesity, but also to other cardiovascular risk factors (e.g., diabetes, dyslipidemia, hypertension, and insulin resistance), researchers have proposed that it might be related to a much larger group of risk factors, called “metabolic syndrome” (Velasquez 2010; Katz 2010).

Recent studies have shown that physical activity and diet programs (alone or in combination) are associated with a reduction in pain, as well as functional improvement among overweight or obese adults with OA (Brosseau 2011). In cases where patients are too obese to engage in physical activity, bariatric surgery has also been correlated with improvements in pain and function among patients with OA of the hip and knee (Gill 2011).

Metabolic Factors Associated with Osteoarthritis

Several interrelated metabolic factors also contribute to osteoarthritis onset and progression; chief among which areinflammation, mitochondrial dysfunction, and oxidative stress.

• Inflammation– Osteoarthritis (OA), like many other age-related diseases, is tied to excessive inflammation (Goldring 2011).

Over-indulgence in foods rich in pro-inflammatory omega-6 fatty acids and insufficient intake of foods rich in anti-inflammatory omega-3 fatty acids characterizes the dietary pattern of most modern, industrialized nations.

Arachidonic acid (an omega-6 fatty acid) is the raw material used by the body to synthesize numerous inflammatory mediators, including leukotriene B4, prostaglandin E2, and thromboxane A2, all of which contribute to pain, swelling, and joint destruction (see figure 1) (Liagre 2002; Devillier 2001; Kawakami 2001).

• Mitochondrial dysfunction – Mitochondriaare the power cores of our cells; they generate the energy that cells need to function. With age, mitochondrial function deteriorates, leading to a variety of negative consequences (Vaamonde-Garcia 2012; Cillero-Pastor 2008; Blanco 2004).

In the case of OA, dysfunctional mitochondria conspire with inflammation to augment joint destruction. One study found that the inflammatory propensity of chondrocytes was amplified when their mitochondria were dysfunctional. Specifically, mitochondrial dysfunction in chondrocytes is associated with increased reactive oxygen species production and activation of the “master-regulator” of inflammation, nuclear factor-kappa B (Nf-kB) (Vaamonde-Garcia 2012).

Fortunately, adhering to a plant-based diet rich in dietary antioxidants, reduced in saturated fat, and balanced in omega-6 and omega-3 fats, such as the Mediterranean diet (see Nutritional Interventions section below) may be an effective means of targeting several of the metabolic imbalances that affect OA.

• Oxidative stress – Oxidative stress, which is caused by free radicals, is known to be a factor in cartilage destruction and inflammation. These reactive molecules are also involved in pain perception (Ziskoven 2010).

Hormones and Osteoarthritis

After the age of 50, more women are affected by osteoarthritis (OA) than men (Bijlsma 2011); this female preponderance suggests that hormone abnormalities may influence the progression and development of the disease (Tanamas 2011).

The link between hormones and OA is further supported by evidence linking hormone (e.g., estrogen) deficiencies to an increased risk of osteoarthritis (Parazzini 2003).

In addition, some evidence suggests that hormone replacement therapy can relieve symptoms of OA, especially among postmenopausal women (Song 2004). As a result, Life Extension encourages OA patients to test for hormone deficiencies and correct them when identified.

Further reading is available in the Female Hormone Restoration protocol.

(Aldamiz-Echevarria 2007; Wixted 2010; Simopoulos 2011; Schror 2011; Bengmark 2006; Murias 2004; Oz 2008; Keicher 1995; Prasad 2004; Safayhi 1992)

Arthritis – Osteoarthritis

Symptoms And Diagnosis

Osteoarthritis (OA) is diagnosed based upon medical history and clinical examination (Busija 2010).

Radiographic imaging can aid in the diagnosis of OA. It involves the identification of a variety of anatomic abnormalities such as joint space narrowing, bone spurs, and joint bone deformity (Murphy 2012). However, since many patients with joint abnormalities do not develop symptoms, a diagnosis of OA cannot be made solely upon the basis of positive radiographic images. Likewise, patients with symptoms of OA may not display radiographic evidence (Bijlsma 2011).

A newer method of imaging called delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) provides information about cartilage quality and may offer an improved means of diagnosing OA in the early stages (Siversson 2012). This method involves the intravenous injection of a negatively charged contrast agent, which then diffuses into articular cartilage over at least two hours. An increased concentration of contrast agent (in positively charged areas on the MRI scan) would be indicative of articular cartilage damage in that specific region (Taylor 2009).

Arthritis – Osteoarthritis

Conventional Treatment

Since there is no cure for ostheoarthritis (OA), most available treatments are aimed at controlling pain and maintaining joint function (Kapoor 2011). If OA pain is unable to be controlled with less invasive measures like physical therapy and exercise, treatment options ranging anywhere from intermittent use of analgesics to total joint replacement surgery are available (Strand 2011).

Physical Therapy/ Exercise

In most cases, osteoarthritis (OA) treatment should begin with the safest and least invasive therapies (e.g., exercise) (Sinusas 2012). This is because physical activity is associated with significant health benefits among OA patients (e.g., preventing obesity, conserving physical function, and contributing to normal joint health) (Egan 2010).

Exercise programs consisting of muscle strengthening and range-of-motion movements are associated with significant improvements in OA symptoms (Sinusas 2012). Similarly, aerobic activity can reduce pain and disability in people with OA of the knee (Jansen 2011).

In patients who are either unable or unwilling to participate in vigorous exercise, walking for approximately 30 minutes per day, at least 3 days per week, can contribute to a reduction on OA symptoms (Ng 2010).

Pharmacological Treatment and Other Therapies

Acetaminophen. Acetaminophen is usually the first-line pharmacologic therapy in conventional medicine for osteoarthritis (OA) (Lim 2011; Woodcock 2009). If acetaminophen is unsuccessful, the next pharmacological treatment level varies depending upon patient-specific factors (e.g., treatment success), but usually involves the use of one or more of the following options (Lim 2011; Scheiman 2010; Howes 2011):

• Topical non-steroidal anti-inflammatory drugs (NSAIDs)
• Topical capsaicin
• Oral NSAIDs
• Intra-articular corticosteroid and hyaluronic acid injections
• Opioids

The Potentially Lethal Side Effects of Over-the-Counter Pain Medications

In an effort to relieve suffering, many ostheoarthritis (OA) patients turn to non-prescription over-the-counter (OTC) analgesics such as acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs) (Hersh 2007). However, since these drugs do not require a prescription, patients may incorrectly assume that they do not need to be as careful about safety as they would with a prescription analgesic. Therefore, it is important for patients to become educated about serious adverse side effects that can occur with popular non-prescription OTC analgesics (Wilcox 2005).

Acetaminophen is one of the most widely used analgesics in the United States. In 2008, approximately 25 billion doses of acetaminophen were sold in the US alone (FDA 2009). Unintentional acetaminophen overdose is responsible for approximately 15,000 hospitalizations each year, and is the leading cause of acute liver failure in the US (Woodcock 2009).

Patents taking acetaminophen should follow these recommendations (Saccomano 2008):

• Do not to exceed a maximum dose of 4 grams/day
• Remember that many prescription pain medications also contain acetaminophen
• Recognize that acetaminophen is also called APAP, paracetamol, and acetyl-para-aminophenol
• Do not use with other NSAIDs (without medical consultation), which increase the risk of kidney toxicity
• Do not take with alcohol, which significantly increases the risk of liver toxicity
• For those taking acetaminophen for pain relief, aggressive supplementation with hepato-protective nutrients such as N-acetyl-cysteine(NAC) and milk thistle extract may provide a means of reducing drug-induced liver damage (Abenavoli 2010; Bajt 2004).

NSAIDs such as ibuprofen and naproxen are also associated with significant adverse effects such as gastrointestinal bleeding, peptic ulcer disease, high blood pressure, edema (i.e., swelling), kidney disease, and heart attack (Peterson 2010). For example, long-term use of NSAIDs can lead to impaired glomerular filtration, renal tubular necrosis, and eventual chronic renal failure by disrupting prostaglandin synthesis, which can impair renal perfusion (Weir 2002). Even in NSAID users without overt kidney dysfunction, subclinical irregularities in kidney function are often observed (Ejaz 2004).

Aspirin (a type of NSAID) is commonly used to treat minor aches and pains, as well as being recommended at low doses for heart protection and stroke prevention. Aspirin irreversibly inhibits an enzyme called cyclooxygenase-1 (COX-1) in platelets, which is why it poses a greater risk of bleeding (i.e., hemorrhage) than other NSAIDs (Hersh 2007). Therefore, patients taking aspirin should avoid the simultaneous use of anticoagulant drugs and/or alcohol (without talking to their doctor first). Aspirin can also cause mild side effects such as heartburn, nausea, vomiting, stomach ache, ringing in the ears, hearing loss, and rash (NIH 2011).

Arthritis – Osteoarthritis

Emerging Therapies

Tanezumab

Tanezumab is an antibody that targets nerve growth factor (NGF), which plays a significant role in pain transmission (Cattaneo 2010). Among patients with osteoarthritis (OA) of the knee, tanezumab was associated with a significant reduction in pain intensity (Felson 2011). However, in June 2010, the FDA put all trials of tanezumab on hold because a significant number of patients taking this drug experienced an unusually rapid progression of joint bone necrosis (Lane 2010). Some researchers claim this bone necrosis occurred because of overuse of the joint (due to the potent analgesic effect of tanezumab). However, the FDA is waiting for more information on the exact cause of this adverse effect before allowing trials to continue (Wood 2010; Lane2010).

Stem Cells

Autologous stem cell transplantation, which utilizes stem cells extracted from one’s own body, as opposed to an embryo, mightreverse painful joint deterioration caused by osteoarthritis (OA). It involves using undifferentiated cells that can develop into almost any tissue—new cartilage, tendons, ligaments, even bone—to replace damaged, arthritic joints (Centeno 2008).

Unlike embryonic stem cells, mesenchymal stem cells (MSCs) have already differentiated to some extent, “committing” to develop into tissues such as bone, muscle, tendon, ligament, and cartilage. They can be found in abundance in bone marrow. Under the proper conditions, MSCs can be induced to differentiate into each of their potential specific tissue types, making them ideal for implanting into damaged joints and bones (Jorgensen 2004).

By using MSCs from your own body (autologous), there is no risk of transplant rejection. There is even evidence that transplanted MSCs exert anti-inflammatory, immune-modulating influences within the joint (Ringe 2009; Chen 2008). This means they can theoretically outperform more traditional transplants, which run the risk of destruction by inflammation.

Two seminal reports presented the results of an early human case-report – an individual with a long history of chronic knee pain that proved unresponsive to surgery (Centeno 2008a; Centeno 2008b).

The patient underwent successful harvest, expansion (through platelet-derived tissue factors), and transplant of his own MSCs into his damaged knee joint. The results were compelling—just one month after the injection the patient’s cartilage surface had expanded by approximately 20%, a gain that was maintained at three months. The meniscus (cartilaginous tissue that provides structural support) was nearly 29% larger in volume at 3 months, indicating vigorous growth and remodeling of previously damaged tissue. The patient’s pain level decreased as well.

Apitherapy

Apitherapy, the use of bee venom for medicinal purposes, including relieving joint pain, can be dated back to at least the 5th century BC (Alqutub 2011). More recently, there have been numerous anecdotal reports of bee stings dramatically improving symptoms of OA (Mayo Clinic 2009b). Bee venom, when combined with acupuncture for the treatment of OA of the knee, was associated with a substantial analgesic effect compared to traditional (needle-only) acupuncture (Kwon 2001). Researchers believe that the anti-inflammatory characteristics of bee venom can be attributed to mellitinin, a component of bee venom that is one hundred times stronger than the inflammation-reducing hormone cortisone (Alqutub 2011).

Arthritis – Osteoarthritis

Arthritis – Osteoarthritis

Life Extension Suggestions

Joint Structure Support

• Glucosamine sulfate: 400 – 3200 mg daily
• Hyaluronic acid(as Hyal-Joint™): 40 mg daily
• Methylsulfonylmethane(MSM): 3000 – 6000 mg daily
• Solubilized Keratin: 300 mg daily
• Chondroitin sulfate: 450 – 3600 mg daily
• S-adenosylmethionine(SAMe): 200 – 1200 mg daily in divided doses

Nutrients To Ease Inflammation

• Fish oil(with olive polyphenols): providing 1400 mg EPA and 1000 mg DHA daily
• Curcumin(as highly absorbed BCM-95®): 400 – 800 mg daily
• Boswellia serrata(as highly absorbable AprèsFlex™): 100 mg daily
• Korean angelica extract(as Decursinol-50™): 200 mg daily
• Krill oil(blended with astaxanthin and sodium hyaluronate): 350 mg daily
• Ginger, standardized extract: 150 – 300 mg daily
• Undenatured type-II collagen(UC-II®): 10 mg daily
• Bromelain(enteric coated): 500 – 1000 mg daily
• Soy and Avocado unsaponifiables: Per label instructions
• Vitamin D: 5000 – 8000 IU daily; depending upon blood levels of 25-OH-vitamin D

Antioxidants

• Green tea, standardized extract: 725 – 1450 mg daily Vitamin C: 1000 – 2000 mg daily
• N-acetyl-cysteine(NAC): 600 – 1800 mg daily
• Milk thistle, standardized extract: 750 mg daily

Additional Support

• Multivitamin and mineral: Per label instruction
• Capsaicin(topical): Per label instructions
• Boron(as calcium fructoborate as patented FruiteX B® OsteoBoron®): 1.5 mg daily
• Gamma Linolenic Acid(GLA): 300 – 600 mg daily
• Pyrroloquinoline quinone(PQQ): 10 – 20 mg daily
• Coenzyme Q10(as ubiquinol): 100 – 300 mg daily
• Trans-resveratrol: 100 – 500 mg daily