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Metabolic Osteoarthritis 101

Osteoarthritis Osteoarthritis

Defining the relationship between metabolic syndrome and osteoarthritis and how to approach it naturally.

As a chiropractor, I see a great deal of people present with osteoarthritis (OA). It is a condition that, until now, has been associated with a fairly straightforward etiology. Two primary causes have been identified and have served as the driving forces behind therapeutic strategies. The following represent those two categories:

Primary: This cause is attributed to “wear and tear” and typically presents around 55-60 years of age. It is claimed by many that this type of OA is unavoidable. If you use a joint for long enough, a breakdown of joint tissue will occur and OA will develop.

Secondary: This type of OA results from another condition such as an injury, obesity, genetics, inactivity or inflammatory conditions. Sidenote: Rheumatoid arthritis serves as an accurate predictor of OA later in life.

Today, a relatively new theory has emerged as another possible underlying cause of OA. According to 2012 Nature Reviews Rheumatology, “Metabolic osteoarthritis (OA) has now been characterized as a subtype of OA, and links have been discovered between this phenotype and metabolic syndrome (MetS).” This distinction is significant for everyone dealing with either MetS patients or OA patients from a functional perspective.

A New Perspective

Typically in practice when you’re managing a patient suffering with osteroarthritic symptoms, the goal is to recommend strategies to increase mobility and decrease pain. This can include therapies such as chiropractic, physical therapy or other manual therapies to achieve these goals. With many of my patients that have been diagnosed with osteoarthritis, they’ve often been told that it is something they simply have to live with (my personal favorite phrase told to patients is, “You’re just getting old.”). While that may be true for some people who have irreversible osteoarthritic damage, when you dig a bit deeper there can be significant physiologic connections to another prevalent disorder, metabolic syndrome.

Since about 2012, researchers have been discussing a dynamic and interactive relationship between an altered metabolism and subsequent joint dysfunction. Recommending glucosamine and chondroitin for the joint pain simply doesn’t address that relationship—helping bring balance and relief to both systems involved. And for roughly half the patients I see (a similar figure heard from fellow practitioners), glucosamine simply isn’t effective. If the underlying cause is continually driving joint destruction, glucosamine, or any other straight joint support formula, doesn’t stand a chance.

The Physiology Behind Metabolic OA

As we saw with Secondary OA, obesity can be implicated in joint dysfunction and discomfort as a result of the undue pressure excess weight places on the joints. Recently, however, researchers have discovered that leptin, a peptide hormone, and adipokine associated with obesity, may actually play an important role in the degradation of cartilage.1 In fact, several links between adipokines like leptin and bone and joint health have been described.1

Given that we know leptin levels are high in the obese body and we know that fat tissue is complicit in joint health, we can look at whether or not leptin impacts cartilage degradation—and if so, how.1 First, it’s important to understand that the link between leptin levels and metabolism has been shown in various contexts; for example, researchers have found that synovial fluid (SF) leptin levels correlate significantly with both BMI (body mass index) and waist circumference.2

That correlation matters because we know that metabolic health can be affected by inflammation, that leptin correlates with metabolic parameters like waist circumference, and that leptin resistance is present with obesity. It stands to reason that a connection between leptin and inflammation may exist. In fact, studies have shown that leptin actually acts as a pro-inflammatory adipokine that upregulates proteolytic enzymes, working in synergy with other pro-inflammatory stimuli.3

The CRP Connection

C-Reactive protein (CRP) is also involved in this cascade of events. While many studies have shed light on leptin’s role, how does CRP fit into this process specifically? CRP is increases in response to secretion of IL-6 by macrophages and T cells. It is also synthesized in the liver in response to secretory factors released by macrophages and adipocytes, such as leptin.

The connection to joint health and elevated CRP levels is nothing novel at this point. However, it correlates with adiposity and leptin levels. This connection is more firmly established due to the circulating CRP impairing leptin signaling and contributing to leptin resistance. Knowing this relationship between CRP and leptin, we can examine the impact of this interplay on the process of cartilage degradation.

Researchers have found that leptin stimulates some of the key-mediating agents in cartilage degradation, such as the aforementioned interleukins. Further, the primary proteinases involved in the process of cartilage turnover include metalloproteinases—of which leptin is a known modulator.4 In fact, in “Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases,” researchers have clearly displayed the connection between leptin and cartilage degradation, concluding that: “Leptin acts as a(n)…adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other…stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis.”3

Natural Support for Metabolic OA

Joint support aimed specifically at patients who also work to support healthy metabolic functions is a novel approach to musculoskeletal supplementation, but given the above information, one worth consideration. Two key ingredients that have been shown to provide support specific to the mechanisms inherent to metabolic OA.

OralVisc acts using HA-Leptin (a hyaluronic acid preparation). The combination of glycosaminoglycans (GAGs) in HA-Leptin has demonstrated both anti-adipogenic and pro-chondrogenic effects in in vitro studies. In animal studies, obese rats treated with Oralvisc showed a higher fat loss, reduction in leptin levels and greater insulin sensitivity. Further, this preparation has been studied in humans for its relationship to pain experienced by obese, knee osteoarthritis patients. The results showed that Oralvisc supports normal leptin levels in the synovial fluid, as well as normal joint function.5

The study outlined the application of Oralvisc in a patient base with concurrent obesity and structural changes in the knee joints. This was a double-blind, randomized, placebo-controlled study of 40 subjects over a period of three months. Visual analog scale, Western Ontario McMaster pain, and WOMAC function scores were recorded. Serum and synovial fluid were measured by enzyme-linked immunosorbent assays for cytokines, bradykinin and leptin. Both serum and synovial fluid samples showed significant decreases for a majority of cytokines, leptin and bradykinin in the oral hyaluronic acid preparation group. Heavy water analyses revealed a significant decrease in hyaluronic acid turnover in the synovial fluid of the treatment group.5

In 2013, 51 symptomatic knee OA patients were recruited sequentially at the time of an outpatient visit for OA documented by either MRI or radiograph. Subjects were between the ages of 50-75 years, had knee effusion and marked their own pain visual analog scores (VAS) >50mm on a 10 cm line. There was a significant decrease between the initial and final serum and synovial fluid leptin levels in the Oralvisc group (p>0.05) as measured by immunoassay. There was also a significance decrease in the Oralvisc serum and synovial final leptin levels as compared to placebo. There was no significance in the relationship of BMI or metabolic syndrome scores to initial or 12 week Oralvisc usage to leptin levels. However, the Oralvisc group lost an average of 0.55 kilograms compared to a 0.75 kilogram weight gain in the placebo group over the 12 wks. These data were as yet unpublished, but were presented to attendees at the ORS (Orthopedic Research Society) 2013 Annual Meeting.

Hops extract is another compound that can support metabolic OA through a dual action mechanism. Hops extract has long been associated with supporting healthy insulin signaling and metabolic processes. One specific extract, Perluxan, has also demonstrated its impact on joint health.

Perluxan includes a proprietary hops resin extract, standardized to contain high concentrations of alpha acids that have been clinically demonstrated to offer rapid support. Extensive research on the properties and abilities of Perluxan has shown that it supports normal expression of the COX-2 enzyme and only moderate inhibition of the COX-1 enzyme, indicating it may be ideal for patients concerned about GI (gastrointestinal) distress.6,7

One study that demonstrates the impact that Perluxan can have on joint health was a double blind, placebo-controlled randomized trial that evaluated the effects of 14 days of Perluxan oral supplementation. “Thirty-six subjects completed a questionnaire to evaluate joint comfort levels at baseline. The time to perform a 20-meter walk on a flat surface was also recorded. Study participants were then assigned to take either Perluxan or a placebo. On day 15, the time to perform a 20-meter walk on a flat surface was again measured and improvements in joint function were assessed. Results indicated Perluxan intake provided fast-acting relief; significant improvement over placebo could be measured only two hours after ingestion of the first dose. Perluxan significantly improved parameters of joint comfort, including relief while in bed, sitting, lying and walking on a flat surface all of which are hugely impacted in patients in need of joint support.”8

Armed with the research concerning leptin, CRP, joint health and metabolic health, and this new approach to supporting both systems involved has the capability to change the way every practice type manages joint pain patients.


1 Toussirot E, Streit G, Wendling D. The Contribution of Adipose Tissue and Adipokines to Inflammation in Joint Diseases. CMC. 2007;14(10):1095-1100.

2 Gandhi R, Takahashi M, Syed K, Davey J, Mahomed N. Relationship between body habitus and joint leptin levels in a knee osteoarthritis population. Journal of Orthopaedic Research. 2009:n/a-n/a. doi:10.1002/jor.21000.

3 Hui W, Litherland G, Elias M et al. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Annals of the Rheumatic Diseases. 2011;71(3):455-462.

4 Castellucci M, De Matteis R, Meisser A, et al. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Molecular Human Reproduction. 2000;6(10):951-958.

5 Nelson F, Zvirbulis R, Zonca B et al. The effects of an oral preparation containing hyaluronic acid (Oralvisc) on obese knee osteoarthritis patients determined by pain, function, bradykinin, leptin, inflammatory cytokines, and heavy water analyses. Rheumatol Int. 2014;35(1):43-52.

6 Lemay M, et al. A dietary supplement is a selective COX-2 inhibitor both in vitro and ex vivo in healthy human volunteers. Nutrilite Health Institute, Access Business Group LLC, Buena Park CA.

7 Jager R, Purpura M. Efficacy of Oral Perluxan Intake: A Randomized, Double-Blind Study. Pharmachem Laboratories, Kearny, NJ.

8 Perluxan Softgels. 1st ed. Los Angeles: Soft Gel Technologies, Inc.; 2014:5.

Dr. Adam Killpartrick earned his degree from Palmer College of Chiropractic in Davenport, IA. His primary practice focus has been a synergistic blend of NUCCA (upper cervical chiropractic) with Cranial Release Technique, for which he has attained lead instructor status. Dr. Killpartrick furthered his education in clinical nutrition, functional diagnostics and lifestyle medicine, and has since successfully integrated this blend of specialized chiropractic care and functional medicine into his New Hampshire private practice. This practical experience led him to clinical consulting for numerous nutritional supplement companies. He is currently the chief scientific officer for DaVinci Laboratories.