Oral Glucosamine in The Treatment Of Temporomandibular Joint Osteoarthritis: A Systematic Review Part 1

Abstract: Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative,  bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic, and anti-catabolic properties,  oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. This review aimed to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA based on the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA based on the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw general recommendations for the use of oral glucosamine in the treatment of TMJ OA.

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Keywords: glucosamine; temporomandibular disorders; temporomandibular joint osteoarthritis; temporomandibular joints 

1. Introduction

The term temporomandibular disorders (TMDs) refers to different musculoskeletal and neuromuscular disorders that affect the temporomandibular joints (TMJs), masticatory muscles, and surrounding tissues [1,2]. According to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), there are three major groups of TMDs: pain-related TMDs (myalgia, arthralgia, headache attributed to TMD), intra-articular TMDs (disc displacement with reduction, disc displacement with reduction with intermittent locking,  disc displacement without reduction with limited opening, disc displacement without reduction without limited opening), and degenerative joint disease (DJD), including temporomandibular joint osteoarthritis (TMJ OA), and subluxation [2]. TMDs are the most common non-dental cause of orofacial pain [3].

The etiology of TMDs is multifactorial. Within the literature, several different factors have been listed, that may lead to the development of TMDs, including trauma, psychosocial factors, systemic factors (comorbid diseases, i.e., rheumatologic, endocrine, neurologic, myopathies, fibromyalgia, insomnia, irritable bowel syndrome), local factors (nonspecific orofacial symptoms, including stiffness, soreness, cramping), and genetic factors [4].

TMDs occur approximately in 31% of adults and 11% of adolescents [5]. The most common type of TMDs is disc displacement with reduction [5,6]. Although the prevalence of TMDs in the general population is relatively high, only up to 5% of those patients require treatment [7].

Patients who suffer from TMDs most often seek treatment because of the pain in the area of the TMJ and/or due to the limited mouth opening. Therefore, the treatment aims to reduce joint pain, increase the maximum mouth opening, prevent further joint damage, and improve a patient’s overall quality of life [8].

There are several different methods of treatment of TMDs. Those methods may be allocated into one of the three categories, including conservative methods of treatment,  minimally invasive surgical procedures, and invasive surgical procedures [9–11]. Conservative methods of treatment are the most common ones and encompass counseling,  physiotherapy, occlusal splint therapy, and pharmacotherapy [4,9]. Conservative methods of treatment are effective in pain relief in patients diagnosed with intracapsular TMD [12]. Occlusal splint therapy and physiotherapy, combined,  are currently most often recommended for patients diagnosed with TMD [12,13]. Pharmacotherapy is considered to be the complementary therapy in the treatment of TMDs,  especially for pain reduction [9]. The most commonly used drugs in pain alleviation in the area of TMJs are nonsteroidal anti-inflammatory drugs (NSAIDs) [14]. However, there are also some other substances, which may be very beneficial for TMJs. One of those is glucosamine, which presents anti-inflammatory and antioxidative properties, among others [15].

Glucosamine is an amino monosaccharide that is naturally biosynthesized in the human body [16]. Glucosamine is a fundamental component of mucopolysaccharides,  glycosaminoglycans. Glycosaminoglycans are attached to the protein core and form proteoglycans, which are part of the extracellular matrix of the articular cartilage [17]. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) [18]. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group strongly recommended the use of crystalline glucosamine sulfate as a step 1 long-term background treatment for the treatment of knee osteoarthritis [19]. Moreover, they discouraged to use other forms of glucosamine [19]. Within the literature, the use of glucosamine has also been recommended for the treatment of hip osteoarthritis [20,21], as well as hand osteoarthritis [21]. There is also limited evidence that glucosamine sulfate appeared to be potentially beneficial in the treatment of ankle osteoarthritis [22]. Although the abovementioned recommendations seem obvious, they are not as clear when related to the treatment of TMDs, including temporomandibular joint osteoarthritis (TMJ OA).

Therefore, this systematic review aimed to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA based on the literature.

2. Materials and Methods 

2.1. Search Strategy

This systematic review was performed concerning the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and SCOPUS databases were searched for randomized clinical trials and randomized clinical studies assessing the efficacy of glucosamine in the treatment of temporomandibular joint osteoarthritis. The databases were searched for manuscripts published in English until 31 December 2022.

The PubMed database was analyzed with the keywords: (“temporomandibular joint” (MeSH Terms) OR (“temporomandibular”(All Fields) AND“joint”(All Fields)) OR “temporomandibular joint”(All Fields) OR (“temporomandibular”(All Fields) AND “joints” (All Fields)) OR “temporomandibular joints”(All Fields)) AND (“disease” (MeSH Terms) OR “disease”(All Fields) OR“disorder” (All Fields) OR“disorders” (All Fields) OR“disorder s” (All Fields) OR “disordes” (All Fields) OR (“osteoarthritis” (MeSH Terms) OR“osteoarthritis” (All Fields) OR “osteoarthritides” (All Fields))) AND (“therapeutics” (MeSH Terms) OR “therapeutics” (All Fields) OR“treatments” (All Fields) OR “therapy” (MeSH Subheading) OR “therapy” (All Fields) OR “treatment” (All Fields) OR “treatment s” (All Fields)) AND (“glucosamin” (All Fields) OR “glucosamine” (MeSH Terms) OR“glucosamine” (All Fields) OR “glucosamines” (All Fields)).

The SCOPUS database was analyzed with the keywords: ((“temporomandibular joints”) AND ((“disorders”) OR (“osteoarthritis”)) AND (“treatment”) AND (“glucosamine”)).

2.2. Clinical Question

What is the efficacy of orally administered glucosamine in the treatment of TMJ OA based on the literature?

2.3. Selection Criteria 

Having removed the duplicates, two of the reviewers (M.D. and B.G.) independently analyzed the manuscripts for eligibility. In the case of disagreement, the abovementioned authors consulted the third reviewer (E.P.).

We used the PICO approach to properly develop literature search strategies for this review:

Population:

Treatment of TMJ OA with glucosamine administered orally

Comparison:

Different pharmacological treatments: occlusal splints, placebo, no treatment.

Outcome: 

Decreased pain in the TMJ area based on the visual analog scale (VAS), and increased maximum mouth opening, measured in millimeters (mm).

We included only randomized clinical trials and randomized clinical studies on adult humans who were diagnosed with TMJ OA. We excluded: (1) animal studies, (2) studies on children, (3) retrospective cohort studies, (4) studies without a control group, (5) articles published in a language other than English, (6) comments, (7) case reports, (8) reviews and meta-analyses.

2.4. Cohen’s Kappa Coefficient

The Cohen’s kappa coefficient between the reviewers was 1.00.

2.5. Risk of Bias Assessment

Risk of bias of the selected manuscripts was performed following the Cochrane Handbook for systematic reviews of Interventions version 6.3 (updated February 2022) [23]. Each manuscript was evaluated by two of the reviewers (M.D. and B.G.) independently and in the case of disagreement, the results were consulted by the third reviewer (E.P.).

3. Results 

Having analyzed the PubMed and Scopus databases, we found 50 references by electronic search. There were 15 duplicates, which were removed. Therefore, 35 records remained. Twenty-seven references did not meet the eligibility criteria and were excluded. Within the excluded records there were: two articles published in a language other than English, 15 reviews, one comment, two animal studies, two studies without a control group,  one case report, one retrospective cohort study, and three studies excluded because of other reasons (unclear methodology regarding the use of glucosamine). Finally, there were eight studies included in this systematic review.

Figure 1 presents the PRISMA flow diagram for the review of the literature.

The selected studies were published between the years 2001 and 2021. Table 1 presents the effectiveness of the orally administered glucosamine used in the treatment of TMJ OA, based on the studies included in the systematic review [24–31].

Glucosamine sulfate administered orally, as the only method of treatment in patients with TMD, appeared to be superior to ibuprofen in terms of pain reduction in the area of TMJs [24,25], as well as in terms of increasing maximum mouth opening [25]. Although glucosamine sulfate combined with chondroitin sulfate and tramadol led to a significant pain reduction in the area of TMJs, only glucosamine sulfate combined with chondroitin sulfate was successful in increasing maximum mouth opening [26]. When glucosamine was compared only to placebo, it appeared that after 3 months, not only did the patients present decreased pain in the area of TMJs, but also decreased sounds within TMJs, and needed a decreased number of over-the-counter medications [27]. However, in short-term (6 weeks) observation oral glucosamine was not superior to placebo [28]. Patients who were supplemented glucosamine additionally, through intra-articular injections of hyaluronic acid, did not benefit in the short-term but presented significantly decreased pain levels and significantly increased maximum mouth opening in the long-term (1 year) observations [29,30]. Glucosamine administered additionally to single-session arthrocentesis and the intra-articular injection of HA did not lead to better clinical results than those which were obtained by the patients who had not received oral glucosamine [31]. This confirms that arthrocentesis of TMJs is a very effective, minimally invasive surgical procedure, as previously reported in the literature [11].

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