Table 1.

Effectiveness of the orally administered glucosamine used in the treatment of TMJ OA, on the basis of the studies included in the systematic review [24,25,26,27,28,29,30,31].

Reference	Study Design	Participants and Intervention	Endpoint and Results
Thie et al. (2001) [24]	Randomized, double-blind study	45 patients (40 women, 5 men) qualified for the study, 39 patients completed the study Diagnosis: degenerative joint disease in at least one of the TMJs Imaging of TMJs: CT Study groups: - glucosamine sulfate 500 mg tablets taken q8h (21 patients, mean age: 36.62 ± 10.3 years) - ibuprofen 400 mg tabelts taken q8h (18 patients, mean age: 38.73 ± 13.3 years) - all of the patients were also allowed to take acetaminophen 500 mg for pain breakthrough	Endpoint: 3 months (90 days) Both the ibuprofen and glucosamine led to a significant reduction in pain levels in patients with DJD. Patients who received glucosamine presented statistically significant improvement of functional pain evaluation and an overall pain interference compared to patients who received ibuprofen.
Haghighat et al. (2013) [25]	Randomized clinical trial	60 patients (46 women, 14 men) Diagnosis: painful TMJ, TMJ crepitation, limitation of mouth opening Imaging of TMJs: none Study groups: - glucosamine sulfate 1500 mg daily for 90 days (30 patients, mean age: 26.60 ± 10.32 years) - ibuprofen 400 mg 2×/day for 90 days (30 patients, mean age: 27.12 ± 10.83 years)	Endpoint: 90 days Patients taking oral glucosamine presented significantly lower TMJ pain intensity during all follow-up appointments and significantly increased mandibular opening following the end of the second month of treatment. Oral glucosamine was recommended as a more effective and safer drug compared to ibuprofen for the treatment of TMJ OA.
Damlar et al. (2015) [26]	Randomized clinical trial	34 patients (34 women, mean age: 28.6 ± 6.89 years) Diagnosis: TMJ internal derangement (Wilkes II or III) Imaging of TMJs: MRI Study groups: - study group: 1500 mg glucosamine sulfate and 1200 mg chondroitin sulfate per day (16 patients) - control group: 50 mg tramadol HCl 2× daily peroral for pain relief (15 patients) - all of the superior and inferior joint spaces were rinsed with 2 mL of saline solution (procedure repeated 10 times)	Endpoint: 8 weeks Both groups presented significantly reduced pain levels after the end of the treatment, whereas significantly increased maximum mouth opening was observed only in the study group. Having compared the changes that occurred within both of the examined groups, the study group presented a significantly decreased concentration of IL-1β and IL-6.
Nguyen et al. (2001) [27]	Randomized, double-blind study	34 patients (30 women, 4 men) Diagnosis: cellulitis, disc displacement, disc dislocation, painful osteoarthritis of the TMJ Imaging of TMJs: no information Study groups: - the active medication group (CS-GH): 3 tablets twice a day for three months, containing glucosamine hydrochloride 250 mg and chondroitin sulfate 200 mg (14 patients, mean age 43 ± 14 years) - the inactive medication group (placebo): 3 tablets twice a day for three months, containing placebo (20 patients, mean age 46 ± 15 years)	Endpoint: 3 months Patients CS-GH presented decreased tenderness in the area of TMJs, decreased sounds within TMJs, and needed a decreased number of over-the-counter medications. Patients who received placebo, reported a significantly decreased pain within the TMJs after the end of the treatment.
Cahlin et al. (2011) [28]	Randomized, double-blind study	59 patients (51 women, 8 men) Diagnosis: presence of osteoarthritis in at least one of the TMJs Imaging of TMJs: lack of precise information Study groups: - the glucosamine sulfate group (glucosmaine sulfate 400 mg): 3 capsules a day for six weeks (30 patients, mean age female: 61 ± 16 years, mean age male: 61 ± 9 years) - the placebo group (placebo 400 mg): 3 capsules a day for six weeks (29 patients, mean age female: 59 ± 8 years, mean age male: 49 ± 11 years) - all of the patients were given 15 tablets of paracetamol (at 1000 mg) as a rescue medication (patients could ask for more tablets if needed)	Endpoint: 6 weeks The effectiveness of oral glucosamine sulfate in TMJ pain reduction, as well as in reduction of TMJ osteoarthritis symptoms, was not better than the placebo.
Cen et al. (2018) [29]	Randomized, double-blind study	136 patients (118 women, 18 men) Diagnosis: TMJ osteoarthritis Imaging of TMJs: CBCT Study groups: - the intervention group (GS + HA): 1 mL sodium HA injection into the superior and inferior spaces of TMJ, repeated in total 4 times (once a week for 4 following weeks) + 2 tablets of glucosamine hydrochloride 240 mg taken 3 times a day for 3 months (67 patients, mean age 40.1 ± 15.8 years) - the control group (placebo + HA): 1 mL sodium HA injection into the superior and inferior spaces of TMJ, repeated in total 4 times (once a week for 4 following weeks) + 2 tablets of placebo 240 mg taken 3 times a day for 3 months (69 patients, mean age 36.2 ± 15.8 years) - all of the superior joint spaces were rinsed with 2 mL of saline solution (3 times) prior to HA intra-articular injection	Endpoint: 1 year In the short-term (1 month) observation, both groups presented a statistically significant increase in maximum mouth opening, statistically significant pain reduction, and significantly decreased concetration of IL-1β and IL-6 (no differences between the groups aparat from the concentartion of IL-6, which was significantly lower in intervention group). After 1 year, patients who received oral glucosamine presented significantly increased maximum mouth opening, significantly decreased pain scores, significantly increased concentration of TGF-β and significantly decreased concentration of IL-1β and IL-6 compared to the control group.
Yang et al. (2018) [30]	Randomized, double-blind study	144 patients (120 women, 24 men) Diagnosis: TMJ osteoarthritis Imaging of TMJs: CBCT Study groups: - group A: 4 intraraticular injections of 2 mL sodium hyaluronate 1×/week + 2 tablets of glucosamine hydrochloride 240 mg 3×/day for 3 months (72 patients, mean age: 40.1 ± 15.8 years) - group B: 4 intra-articular injection of 2 mL sodium hyaluronate 1×/week + placebo pills for 3 months (72 patients, mean age: 36.2 ± 15.8 years) - all of the superior and inferior joint spaces were rinsed prior to HA intra-articular injection - all of the patients received Diclofenac (50 mg) as a rescue medication	Endpoint: 1 year Oral glucosamine supplementation, in short term, had no extra effect on TMJ OA; whereas, in the long-term observations, complementary administration of oral glucosamine led to significant TMJ pain reduction and significant increase in maximum mouth opening.
Kılıç (2021) [31]	Randomized clinical trial	26 patients (23 women, 3 men) Diagnosis: TMJ osteoarthritis Imaging of TMJs: CBCT Study groups: - group 1 (control): single-session arthrocentesis + intra-articular injection of HA (14 patients, mean age: 28.71 ± 10.94 years) - group 2 (study): single-session arthrocentesis + intra-articular injection of HA + 3 months of supplementation of 750 mg glucosamine hydrochloride, 600 mg chondroitin sulfate, and 350 mg methylsulfonylmethane (2 × 1 dosage daily) (12 patients, mean age: 27.92 ± 11.20 years)	Endpoint: 1 year The results obtained in both groups were similar. Both methods of treatment presented a similar effectiveness.

CBCT—cone beam computed tomography, CS-GH—chondroitin sulfate-glucosamine hydrochloride, CT—computed tomography, DJD—degenerative joint disease, G/D—glucosamine/diclofenac, GS—glucosamine, HA—hyaluronic acid, IL-1β—interleukin 1 beta, IL-6—interleukin 6, MRI—magnetic resonance imaging, q8h—every 8 h, TMJs—temporomandibular joints, TGFβ—transforming growth factor beta.