|
Page 1, 2, 3
Epidemiology
Primary osteoarthritis (OA) is common, costly, and crippling. Postmenopausal OA is associated with degeneration, commonly found in hands, knees, and hips. Contributing factors include metabolic, genetic, epigenetic, inflammatory, and mechanical factors. The significance of these interactions is incalculable, but not inconsequential.
In 2009, 40 to 50 million US adults were diagnosed with arthritis.1 In 2003, the arthritides accounted for 1% of the gross domestic product, or nearly $81 billion in medical expenditures and $47 billion in lost earnings.2 The incidence of OA increases with age, rising from 27% in those under 70 years old to 44% in those over 80 years old. Obesity confers the highest lifetime risk.3
Body mass index (BMI) >27 kg/m2 is associated with increased risk for knee OA in a cohort of 3585 persons >55 years old.3 High heels may increase risk of OA due to increased force across the knee joints.4
BMI ≥ 32 kg/m2 is associated with 2 to 3 times the risk for total hip replacement in a study of 1,152,006 Norwegians aged 18 to 67 years.5 41% of people over age 40 have hand OA; women are more affected than men.6
Signs and Symptoms
The symptoms of OA include slowly developing arthralgia, stiffness after stillness, increasing pain as the day progresses, and weakness. Full range of motion is initially uncomfortable and eventually limited. Signs of OA in the hands include limited closure, bony enlargement of distal and proximal interphalangeal joints, carpometacarpal squaring, limited thumb extension, thenar wasting, and thumb in palm formation. In knees, flexion and then extension are limited and motion is often painful and crepitant. Popliteal cysts, cool effusions, vastus medialis obliquus wasting, and valgus or varus deformities can be seen. In the hip, pain is often limited to the groin, inner thigh, or knee alone. Internal rotation is often uncomfortable and limited. Psoas contractures and limited abduction can be seen. X-ray findings can be deceiving! Horrible bone-on-bone osteoarthritis can be seen in an absolutely asymptomatic weight-bearing joint.
Conventional Treatment
Treatments for OA in all sites include weight management, exercise, analgesics, selective and nonselective nonsteroidals (sNSAIDs/nsNSAIDs), topical pharmaceuticals, bracing, special shoes, electrical stimulation, laser therapy, manipulative therapy, physical and occupational therapy, intra-articular steroids, mobility aids (cane, walker, wheel chair), viscosupplementation, arthroscopy, and partial or total joint arthroplasty.
Acetaminophen is weakly analgesic, and narcotics should be reserved for brief perisurgical periods.7 Although NSAIDs are strongly recommended, all NSAIDs increase risk of gastrointestinal bleeding. Both sNSAIDs and nsNSAIDs, excluding aspirin, increase risk of stroke, and myocardial infarction.7 NSAIDs should be used sparingly and for short duration and may be used in concert with acetaminophen. Oral NSAIDs (both types) should not be used in any patient over 75 years of age, as they may cause sodium retention, reduce glomerular filtration and worsen hypertension even with short-term use.7,8 Tramadol provides some relief but its use is limited because of frequent adverse reactions. Topical capsaicin and NSAIDs are modestly efficacious and safe.8 Manipulative therapies should be offered only as adjunct to exercise.7
Hands
Few high-quality randomized controlled trials (RCTs) on hand OA exist. Expert opinion and our clinical experience support the following: evaluation of independent daily living activities, joint protection, work simplification instruction, thermal modalities, and splinting. Intra-articular injection therapies are not recommended in the hand.7
Knees
There are data both supporting and refuting patellofemoral bracing, electrical stimulation, wedged insoles, acupuncture, manual therapy, and shoe modifications.7,9-11
Intra-articular steroids provide brief pain relief and should be used sparingly if at all. Acute adverse reactions are rare but include increased serum glucose, avascular necrosis, acute synovitis, acute calcium pyrophosphate deposition, infection, tendinopathy, and periarticular calcifications. Long-term adverse reactions include capillary fragility, tissue atrophy, joint destruction, and cartilage degeneration.12 The common practice of combining intra-articular steroids and local anesthetic causes chondrocyte death.13 The American Academy of Orthopedic Surgeons (AAOS) does not recommend intra-articular steroid injections, but the American College of Rheumatology does.7,9
Intra-articular viscosupplementation with hyaluronic acid has been recommended for patients with mild to moderate knee OA who have failed conservative treatment, but its efficacy is unproven and it is falling out of favor.5,7,9,12,14 Partial meniscectomy for torn meniscus may be considered, if conservative measures fail, but it is possible to live with a torn meniscus if activity is judicious.9
Hips
Intra-articular steroids can be used, but expensive imaging is needed for proper needle placement and they are not that helpful for ordinary OA. Hyaluronic acid has not been approved for use in the hip. Arthroscopy can be helpful in cases of torn labrum.15 Severe OA of the hip may be tolerated well for years, unlike severe knee OA, which is less tolerated.
Exercise
Exercise must be part of a conventional or integrative approach to OA, but formulating optimal individualized exercise can be challenging. Supervised group exercise is superior to nonsupervised activity.16 Tai chi, qi gong, yoga, and Feldenkrais method have shown positive results. In an observational study, Webb showed improvement in multiple gait parameters in community-dwelling adults with OA after participation in twice-weekly Feldenkrais method classes over a 30-week period.17
Yoga and tai chi are the only disciplines that have been studied using systematic reviews. Cramer found two high-quality studies recommending yoga for OA pain reduction.18 Evidence is currently stronger for tai chi. A systematic review of three high-quality RCTs found that tai chi improved gait and reduced stiffness and pain for knee OA patients.19 Studies have also shown that tai chi increases OA patients' quality of life.20
Exercise reduces pain and improves physical strength, balance, metabolism, and mood. Many OA patients view their bodies as a source of pain, discomfort, and sadness. Exercise forms such as tai chi and yoga can provide pleasure and joy.
Mind-Body Medicine
Living with any chronic pain can be devastating emotionally, socially, financially, and spiritually. A truly holistic treatment plan for postmenopausal OA must address the mind-body connection. Many formalized techniques improve pain, hot flashes, cognitive function, insomnia, and quality of life.21-26 Mindfulness-based stress reduction (MBSR) is one such well-studied system. Designed by Jon Kabat-Zinn, PhD, it teaches somatic awareness and meditation. Ussher found that even 10 minutes of MBSR practice decreased pain compared with controls who read natural history literature.27 Rosenzweig found that an 8-week course in MBSR had the most significant effect on patients with arthritis and back/neck pain compared with other diseases. While still significant, the MBSR program has less effect on headache and fibromyalgia. Patients with concomitant meditation practice had even greater improvements in pain and quality of life.28
Phytochemical and Herbal Treatments
Many phytochemicals and herbs have been studied for OA treatment. This review will focus on epigallocatechin-3-gallate (EGCG), sulforaphane, resveratrol, Curcuma longa, Boswellia serrata, and Harpagophytum procumbens.
EGCG, a phytochemical present in green tea, is being researched intensely for its impact on many conditions, including cerebral hemorrhage, liver disease, infection, cancer, atherosclerosis, inflammatory joint disease, and OA.29
Basic scientists are discovering and elucidating the molecular mechanisms of EGCG; however, good clinical RCTs OA studies have not yet been conducted. An in vitro study of EGCG showed 2 important effects in inflamed chondrocytes; inhibition of IL-1, TGF b, IL-8, and chemokine ligand 2, as well as reduced neutrophil and monocyte migration.30 In another in vitro model, EGCG prevented production of IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MCP-3, and macrophage inflammatory protein-1beta (MIP-1b) via NF-kB in inflamed chondrocytes.31 The chondroprotective role of EGCG may also be due to increased resistance to metalloproteinases 1, 9, and 13.32 EGCG may also work on cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2), TNFa, and advanced glycation end products (AGEs).33,34 Huang stimulated human synovial fibroblasts with IL-1b and found that the application of EGCG inhibited COX-2, PGE2, and IL-8.33
Clearly, human studies are lacking; but, given green tea's safety, it is reasonable to advise drinking high-quality, organic green tea or use a green tea product standardized for EGCG. A rational and well-tolerated starting dose of EGCG is 100 to 300 mg daily.
Curcuma longa is one of the best-studied herbs in the treatment of osteoarthritis. There are abundant in vitro, in vivo, clinical studies, and systematic reviews that support its use. It appears to work by inhibiting IL-1b, IL-6, IL-8, NF-kB, TNFa, MMP-3, MMP-9, MMP-13, caspase-3, and COX-2 and enhancing chondrogenesis.35-41 NF-kB activation can directly trigger matrix degrading enzymes. Curcumin reduces production of AGEs that lead to chondrocyte destruction.36 Interestingly, it appears that curcumin and resveratrol synergistically protect chondrocytes by downregulating NF-kB and reducing pro-inflammatory cytokines.38,42,43 Shakibaei pretreated in vitro chondrocytes with curcumin, resveratrol, or the combination. He then applied IL-1b and observed the catabolic effects. He found that the combination provided superior protection compared with each phytochemical alone.42
Strong in vitro studies of curcumin encouraged in vivo studies for patients with OA. Three well-performed clinical trials support its use in knee OA. Knee OA is easily studied because outcome measures and radiographic features are well characterized. A randomized, double-blind study compared diclofenac 75 mg/d + placebo with diclofenac 75 mg/d + curcumin 1000 mg/d for 3 months. Diclofenac and curcumin demonstrated superiority for decreasing pain and improving function.44 In an in vivo comparison of boswellia (frankincense) + curcumin (500 mg b.i.d.) with celecoxib 100 mg b.i.d., the herbal formulation outperformed celecoxib on symptom scoring. No safety issues were found with the herbal formulation.45
The form of curcumin is critical for absorption. There are multiple proprietary forms of curcumin that enhance absorption. Examples are quality curcumin complexed with phosphatidylcholine, BCM-95 (curcumin with essential oil of curcumin), and curcumin dispersed with colloidal nanoparticles. To date there has not been a study comparing each of these forms with the other, although they each have strong evidence supporting increased absorption. BCM-95 has been shown to have a 6.93-fold increase in absorption compared with standardized curcumin.46 Curcumin dispersed with colloidal nanoparticles was shown to increase blood concentration levels 27-fold higher compared with plain curcumin.47 Curcumin complexed with phosphatidylcholine has shown a 29-fold higher blood concentration level.48 It must be stressed that the absorption research has been performed by industry and each uses different standardized curcumin products as a control.
Curcumin complexed with phosphatidylcholine is the only proprietary form of curcumin that has been studied in patients with osteoarthritis. Belcaro performed a 10-month placebo-controlled study examining clinical efficacy and biometric end points such as IL-1beta, IL-6, and ESR. It proved superior in WOMAC score (a standardized questionnaire to access pain, stiffness, and physical function), Karnofsky Performance Scale Index, and most biometric end points.49 We often start with high-quality curcumin, loading doses between 1 and 3g/d in divided doses for 2 weeks, then decrease to efficacy. If patients are allergic to soy, some forms of curcumin cannot be used.
Boswellia serrata is another herb that has many different formulations. Several forms are standardized for boswellic acid, 5-Loxin, and proprietary resins. One of these resins was studied in a double-blind RCT for efficacy of treating OA pain and dysfunction. While the trial was only 30 days, statistically significant improvement was first seen at day 5, indicating that this form of boswellia may be effective for acute pain management.50 5-Loxin has also been studied in a similar manner. Sengupta studied 2 different dosages of 5-Loxin (100 mg/d and 250 mg/d) and compared them with placebo and followed patients for 90 days.51 This study's strength was that it measured MMP-3 from knee synovial fluid before and after treatment. At the dosages of both 100 mg/d and 250 mg/d, 5-Loxin showed significant improvement in pain at 7 days that continued until study's end. On a molecular level, boswellia shows many similarities to curcumin. There appears to be strong inhibition of iNOS, MMP-9, MMP-13, NF-kB, TNFa, IL-1, IL-2, IL-4, IL-6, and IFNg, and the complement system.52,53
The British Medical Journal recently published a systematic review of RCTs studying boswellia in several diseases. It found encouraging evidence that boswellia was an effective and safe treatment for osteoarthritis.54
Sulforaphane is another promising phytochemical. It belongs to the isothiocyanate group of organosulfur compounds from sprouted cruciferous vegetable seeds, such as broccoli seeds. Intense research on sulforaphane's antineoplastic, antimicrobial, and anti-inflammatory properties is currently being performed. While no human trials in OA patients have yet been performed, we are beginning to understand molecular mechanisms which suggest that it will be efficacious. Sulforaphane appears to activate the cytoprotective transcription factor Nrf2, downregulate NF-kB, decrease MMP-1 and MMP-13, and protect against cartilage degradation in a mouse model and in vitro.55-57
Page 1, 2, 3
|
