Table 2.
Therapeutic interventions with zinc in osteoarthritis and rheumatoid arthritis.
| Disease | Effect (p-Value) | Treatment | Study Method | Reference |
|---|---|---|---|---|
| OA | Increased subchondral plate thickness, reduction of cartilage damage (p < 0.001) | Knockout of ZIP8 | in vivo (Chondrocyte-specific CKO fl/fl mice (Mtf1; Col2a1-Cre)) | Kim, J.H.; et al. [149] |
| OA | Increased serum antioxidative capacity, glutathione levels, and IL-10 levels; lower Osteo-arthritis Research Society International (OARSI) scores (p < 0.05) Reduced IL-1β and MMP-13 expression; increased ROS production (p < 0.05) |
1.6 mg/kg/day of zinc supplementation; 25 μM zinc |
in vivo (n = 5, mono-sodium-induced iodoacetate (MIA) Wistar rats) in vitro (chondrosarcoma cell line (SW1353 cells) treated with 5 μM MIA) |
Huang, T.C.; et al. [150] |
| OA | Decreased cartilage degeneration (cartilage breakdown products TIINE, ARGN, and AGEG) (p < 0.001) | MMP-13 inhibitor PF152 | ex vivo (human cartilage explants) in vivo (n = 60, beagle dogs with OA-induced by partial medial meniscectomy) |
Settle, S.; et al. [165] |
| OA | Chondroprotection | MMP-13 inhibitor 43a | in vivo (n = 2 male Sprague-Dawley IGS rats) (n = 5 male beagle dogs) (n = 2 cynomolgus monkeys) |
Ruminski, P.G.; [166] |
| OA | Reduction of cartilage damage (p < 0.05) |
MMP-13 inhibitor ALS 10635 | in vivo (n = 12, MIA-induced OA male Sprague-Dawley rat) (n = 20 surgical induced OA male Lewis rats) |
Baragi, V.M.; et al. [167] |
| OA | Inhibition of aggrecanase activity (p < 0.001) | Humanized anti-ADAMTS-5 monoclonal antibody, GSK2394002 | in vivo (n = 20 DMM male Swiss Webster mice) |
Larkin, J.; et al. [169] |
| OA | Blockage of IL-6R | ADAM17, ADAM inhibitor, GW280264X |
in vitro (cultured cells) |
Ludwig, A.; et al. [170] |
| OA | Lower use of analgesics (p < 0.001) and /or NSAIDs (p < 0.02), improved WOMAC scale (p < 0.001) |
Phytalgic capsules three times daily: 10 mg zinc citrate, 1371 mg fish oil, 60 mg nettle leaves Urtica dioica L., 12 mg Vitamin E, 12 mg Vitamin C |
Double-blind randomised Controlled Trial (n = 81) |
Jacquet, A.; et al. [151] |
| RA | DAS-28 score and serum hs-CRP (p < 0.01); increased antioxidant markers (TAC, GPX, SOD, and CAT) (p < 0.01) | One Selenplus capsule daily: 50 μg selenium, 8 mg zinc oxide, 400 μg vitamin A, 125 mg vitamin C, and 40 mg vitamin E |
Pre-post Controlled Trial (n = 40 female) |
Jalili, M.; et al. [152] |
| RA | No beneficial effect on inflammation or clinical indices | 220 mg zinc sulphate (45 mg elemental zinc) three times daily | Controlled Trial (n = 18) |
Peretz, A.; et al. [153] |
| RA | No considerable alterations in ROS amounts of monocytes | 130 mg zinc aspartate two times daily | in vivo and in vitro Following treatment with zinc, after in vitro monocyte stimulation with 0.1 mM zinc (II) |
Herold, A.; et al. [154] |
| RA | positive changes regarding joint swelling, morning stiffness, walking time; no improvements regarding grip strength | 220 mg zinc sulfate (45 mg elemental zinc) three times daily | Double-blind Controlled Trial (n = 24) |
Simkin, P.A. [155] |
| RA | Increased phagocytic activity of PMNs; unknown clinical effect (lack of statistical analysis) | 45 mg elemental zinc daily (zinc gluconate) | Controlled Trial (n = 22) |
Peretz, A.; et al. [156] |
| RA | No change in ESR, HCT or joint scores in severe RA patients (lack of statistical analysis) | 220 mg zinc sulfate (45 mg elemental zinc) three times daily | Controlled Trial (n = 22) |
Rasker, J.J.; et al. [157] |
| RA | No statistically significant therapeutic effect; increase of alkaline phosphatase (p < 0.01) | 220 mg zinc sulfate (45 mg elemental zinc) three times daily | Double-blind Randomised Controlled Trial (n = 27) |
Mattingly, P.C.; et al. [159] |
| RA | Greater use of supplemental zinc (p-trend = 0.03) was inversely associated with rheumatoid arthritis | Supplemental zinc (10.4-15.5 mg/day) or food only containing zinc (9.7-13.5 mg/day) |
Prospective cohort study (n = 29,368 females) |
Cerhan, J.R.; et al. [160] |
| RA | Reduced cartilage degradation and disease progression (p < 0.05) | MT1MMP selective inhibitory antibody DX2400 and/or TNFRFc fusion protein | in vivo (CIA-treated mice) |
Kaneko, K.; et al. [163] |
| RA and OA | Inhibition of MMP-9; promotion of survival, invasion and release of pro-inflammatory cytokines by FLS (p < 0.01) | Andecaliximab | in vitro (OA and RA synovial fibroblasts) |
Xue, M.; et al. [164] |