title: The combined therapy with chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride does not improve joint damage in an experimental model of knee osteoarthritis in rabbits.
abstract: Osteoarthritis is the most common chronic joint disorder especially during aging. Although with controversies, glucosamine, both in its forms of sulfate and hydrochloride, and chondroitin sulfate are commonly employed to treat osteoarthritis. Due to the modest improve in the symptoms observed in patients treated with these drugs alone, a formulation combining both agents has been considered. The discrepant results achieved for pain control or structural improvement in osteoarthritis patients has been attributed to the quality of chemical formulations or different bias in clinical studies. The current study has been designed to test the effects of two different combined formulations with adequate pharmaceutical grade of these drugs in osteoarthritic joints, and to explore the underlying mechanisms modulated by both formulations in different osteoarthritis target tissues. Knee osteoarthritis was surgically induced in experimental rabbits. Some animals received the combined therapy (CT)1, (chondroitin sulfate 1200mg/day + glucosamine sulfate 1500mg/day), or the CT2 ((chondroitin sulfate 1200mg/day + glucosamine hydrochloride 1500mg/day). Neither CT1 nor CT2 significantly modified the cartilage damage or the synovial inflammation observed in osteoarthritic animals. Treatments were also unable to modify the presence of pro-inflammatory mediators, and the synthesis of metalloproteinases in the cartilage or in the synovium of osteoarthritic animals. Combined therapies did not modify the decrease in the subchondral bone mineral density observed in osteoarthritic rabbits. Therapies of chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride failed to improve structural damage or to ameliorate the inflammatory profile of joint tissues during experimental osteoarthritis.
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: jaromanblas@gmail.com.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Roman-Blas
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: aranzazu.mediero@quironsalud.es.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Mediero
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: ltardio@fjd.es.
authors.forename: Lidia
authors.initials: L
authors.lastname: Tardío
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: sportal@fjd.es.
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Nuñez
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: paula.gratal@fjd.es.
authors.forename: Paula
authors.initials: P
authors.lastname: Gratal
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: gherrero@fjd.es.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.affiliation: Bone and Joint Research Unit. IIS-Fundación Jiménez Díaz UAM and Cooperative Research Thematic Network on Aging and Frailty (RETICEF), Madrid, Spain. Electronic address: rlargo@fjd.es.
authors.forename: Raquel
authors.initials: R
authors.lastname: Largo
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002809:Chondroitin Sulfates / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005944:Glucosamine / Q000494:pharmacology* / Q000627:therapeutic use; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053244:Osteoprotegerin / Q000096:biosynthesis; D053245:RANK Ligand / Q000096:biosynthesis; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D053244:Osteoprotegerin; D053245:RANK Ligand; D002809:Chondroitin Sulfates; D020782:Matrix Metalloproteinases; D005944:Glucosamine
keywords: Cartilage damage; Chondroitin sulfate; Glucosamine sulfate; Osteoarthritis; Subchondral bone; Synovial inflammation