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From the Townsend Letter
February/March 2014

The Integrated Treatment of Postmenopausal Osteoarthritis
by Alena Guggenheim, ND, and Carla Guggenheim, DO, FACP, with thanks to Nicholas Morgan, ND
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Harpagophytum procumbens (devil's claw) has a long history of use in traditional Western herbalism for arthritis treatment and an established safety record.58 In vitro evidence suggests that devil's claw inhibits TNFa, IL-6, IL-1b, PGE2, NF-kB, and COX-2.59,60 Systematic reviews suggest that a dosage of 60 mg/d harpagoside is effective for knee and hip OA.61 This bitter herb is also a mild diuretic, mild sedative, and appetite stimulant. We find that it is a good choice for anxious patients with sluggish digestion.
The size and quality of trials evaluating herbal interventions is growing rapidly and reaching wider audiences. One such article appeared in Oxford's Rheumatology in late 2013. In a large randomized, double-blind, parallel-efficacy trial of 440 patients, Chopra compared an Ayurvedic formulation of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, and Boswellia serrata with celecoxib (200 mg daily) and glucosamine (2g daily) and found outcomes equivalent at 6 months for all 3 treatments.62

Balneotherapy is a traditional term to describe spa therapies that often include mud packs and hyperosmolar mineral bathing. It is an easy-to-follow, low-cost treatment that can be combined with mindfulness-based meditation.
Mud application to the knee was found to be superior to control for WOMAC and pain scoring in a recent meta-analysis of 7 RCTs.63 The difficulty with this analysis is that the dosage of mud applications and follow-up time period for each study were different. This suggests that a 20-minute application of mud, 5 times weekly for 2 weeks, is effective up to 3 months, although it should be noted that even 3 mud-based therapies combined with mineral bathing over the course of a year have been found to be efficacious.64 Mud therapy has also been compared with intra-articular hyaluronic acid, yielding equivalent results at 6 months; but mud is safer.65 In our experience, mud therapy works well for hand and knee OA but is a difficult treatment for hip OA due to the "messiness" factor.
Many of the studies evaluating balneotherapy have been performed at the Dead Sea or thermal spas in Europe. An observational study found that 2 mineral baths within 2 weeks improved gait, pain, and WOMAC scores.66 Evcik compared mud therapy, mineral bathing, and hot packs applied to the knee for 20 minutes 5 times weekly for 2 weeks and found that all therapies improved WOMAC scores.67
In our practice, recreating mineral baths in the patient's own home is highly effective and well tolerated, as patients find it easy and pleasurable. Patients are instructed to purchase bulk Dead Sea salt and use 5 to 7 cups per 52-gallon bathtub. We often start with 3 to 5 baths per week then taper to once weekly when the patient has stabilized. Water temperature may prove important, but has not been well studied in OA.

Vitamin D
Although the prospect seems sensible, it is controversial whether vitamin D status affects OA disease risk or progression. One epidemiological study suggests that low intake and low serum levels of vitamin D each appear to be associated with an increased risk for progression of knee OA.68 Two RCTs have been performed; one showing benefit in OA patients that had a baseline vitamin D ≤ 50  nmol/L given 60,000 IU daily for 10 days, then 60,000 IU monthly for 12 months.69 The other RCT found no benefit in patients who were dose-escalated to serum 25(OH) vitamin D levels of >36 nmol/L and followed for 2 years.70 It should be noted that both articles had serious limitations in that optimal 25 OH vitamin D levels were never achieved. In clinical practice, we aim to raise patients' serum 25(OH) vitamin D3 levels ~150 nmol/L or 60ng/ml. We base our recommendations on the additional benefits of reducing cancer and osteoporosis risks.

Polyunsaturated Omega-3 Fatty Acids (PUFA-3)
To date, the research supporting the use of long-chain w-3 essential fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is much stronger for inflammatory arthritides such as rheumatoid arthritis. It is a relatively new concept to think about osteoarthritis as an inflammatory process, and thus we have not yet fully explored the use of EPA and DHA for clinical efficacy. From a mechanistic, animal-based model, PUFA-3 decreases IL-1b-mediated cartilage degradation, decreases MMP-2, and improves collagen cross-links.71,72 In humans, our most compelling evidence was performed during the Multicentre OA Study (MOST). Baker examined plasma omega-6 and omega-3 fatty acid levels in 472 adults considered to be at risk of OA.73 Knee synovitis seen on MRI was evaluated in relation to serum fatty acids and cartilage morphology. They found that patients with higher omega-6 plasma levels had increased synovitis, low DHA, and patellofemoral cartilage loss. These data are intriguing but inadequate to provide definitive evidence supporting routine supplementation for OA. Despite this, PUFA-3 therapy has been shown to have an NSAID-sparing effect in RA and has collateral heart protection with a high safety profile.74
If PUFA-3 is prescribed to patients with OA, caution should be taken if the patient is on blood-thinning medications or has a bleeding disorder. Only fish oil that has been third–party verified to be free of PCBs and heavy metals should be used. In light of the Fukushima accident, fish oil may need additional safety testing.

Glucosamine and chondroitin have long been touted as the natural medicine treatment of choice for OA and enjoy more research than any other natural substance. Even after a decade of research, the true efficacy of glucosamine and chondroitin is not clear. Glucosamine appears to work by decreasing IL-1B, NF-kB, MMP-2, MMP9, and COX-2 and via induction of anabolic mediators such as transforming growth factor (TGF)-b1 and connective tissue growth factor (CTGF). Chondroitin shows similar effects by decreasing IL-1B, NF-kB, MMP-1, MMP-3, and MMP-13 and conversely increasing type II collagen and proteoglycan synthesis in human articular chondrocytes.75
RCTs have conflicting outcomes. Most studies have been small or poorly performed. That said, compelling evidence for the clinical use of glucosamine was recently published by Bertin and Taieb.76 They analyzed data from 11,772 patients and found that those who used glucosamine took significantly less NSAIDs. If glucosamine and chondroitin allow a patient to decrease intake of a potentially harmful medication, even when true efficacy is not proven, it is reasonable to prescribe them in a clinical setting.
Glucosamine and chondroitin may not be safe for use in patients with chronic liver diseases, although these data are highly circumstantial.77 We advise caution in treating chronic liver disease patients with glucosamine and chondroitin.

Platelet Rich Plasma (PRP)
It is beyond the scope of this article to fully address the research and impact of platelet rich plasma injection into OA joints. However, given the body of evidence, it should not be overlooked as a safe and effective treatment for many OA patients, especially those facing total joint replacement therapy. The research of PRP is rapidly expanding and has been overall positive. PRP appears to release growth factors that can increase meniscal and chondrocyte growth.78-80 It has been found in multiple trails to be superior to hyaluronic acid injection for pain, function, and radiographic features.81,82

We often tell our patients that no amount of supplements can compensate for poor diets, no matter what the disease. We have just spent a good deal of time discussing the dietary supplements for OA management in women; now we must turn our attention to diet. Unfortunately, diet is an incredibly difficult subject to study within the current scientific paradigm. If we rely on research alone, we can only make broad statements; for example, a diet low in vitamin K or magnesium or high in soda may contribute to disease progression.83-85 Our recommendations on diet are therefore based on our collective 31 years of clinical practice. Most patients are prescribed a diet that is more than 90% vegetables, fruits, raw nuts and seeds, eggs, pasture-raised meat, olive oil, grapeseed oil, and coconut oil. A good diet contains less than 10% grains (whole or refined), dairy, sugars, conventionally raised meat, processed meats, and vegetable oils (corn, peanut, etc.). Patients are also advised to eat 3 cups of cruciferous vegetables and 3 cups of dark leafy greens per day. Helping the patient focus on what to eat, rather than foods to avoid, acts to "crowd out" nutrient-poor dietary choices.
While purely anecdotal, a recent patient story illustrates the importance of diet. A 48-year-old, morbidly obese female presented with severe bilateral knee OA looking for alternatives to knee surgery, which was recently discussed as her only option for care. Fatigue and pain precluded exercise. She was prescribed the diet described above. At 6 weeks she was walking without a cane, able to walk up and down stairs, and had enough energy to start a light exercise program. Then one night she succumbed to food cravings and ate an entire pepperoni pizza. Within 12 hours she was unable to get out of bed and photodocumented her knees more than doubling in size. She spent the next 3 days in bed. Needless to say, she returned to her healthful eating routines and has continued to improve.

Osteoarthritis can be devastating and life changing. Integrative and conventional physicians agree on prevention through diet and exercise. We believe that high-quality supplements are crucial for patient safety, strong clinical studies, and limiting the need for potentially dangerous pharmaceuticals. Patient safety is paramount, pharmaceuticals fall short, regenerative techniques are promising but unproven, and surgery should be a last resort.
Integrative physicians believe that Mediterranean/Paleolithic diets provide energy and substrate for patients to exercise and repair their tissues. We attempt to coach patients through the game of life with osteoarthritis, enabling joyful and easy movement. Because OA risk factors are multifactorial, we believe that utilizing multiple therapies is essential and guides our holistic approach of diet, exercise, meditation, modalities, and nutraceuticals. We have shown that there is growing evidence for each of these synergistic interventions. We strongly encourage future research to include study of medical-grade supplements, excluding inferior products to ensure study validity. We would also like to see multifaceted clinical models to evaluate effectiveness of the holistic approach.

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