title: Early intra-articular injection of alendronate reduces cartilage changes and subchondral bone loss in rat temporomandibular joints after ovariectomy.
abstract: This study investigated the effects of intra-articular injection of alendronate on the mandibular condyle in ovariectomized rats. Sixty rats were divided into five groups: ovariectomy with vehicle treatment alone, early alendronate treatment at ovariectomy, late alendronate treatment at 4 weeks after ovariectomy, sham-operation with vehicle treatment, and normal controls. The changes in cartilage and subchondral bone were evaluated by micro-computed tomography, histology, tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real-time quantitative polymerase chain reaction. Compared with late alendronate treatment, early alendronate treatment completely inhibited cartilage thickening (727.6±39.3 vs. 1013.3±51.6; P=0.017) and improved microstructural properties of the subchondral bone, with a higher bone volume ratio (46.4±2.5 vs. 37.5±2.1; P=0.038), trabecular thickness (47.3±1.7 vs. 34.6±1.4; P=0.029), and trabecular number (8.5±0.6 vs. 6.2±0.3; P=0.041) and lower trabecular separation (30.2±1.6 vs. 37.7±2.6; P=0.034). Fewer TRAP-positive cells (4.2±0.2 vs. 6.8±0.4; P=0.019) and a higher OPG/RANKL ratio (0.38±0.01 vs. 0.25±0.03; P=0.043) in the subchondral bone were observed in the animals with early treatment compared to late treatment or ovariectomy/vehicle treatment. In addition, early alendronate treatment blocked the up-regulation of matrix metalloproteinase (MMP)-13 expression in the chondrocytes, whereas late alendronate treatment attenuated the up-regulation of MMP-13 expression. Our results suggest the therapeutic potential of intra-articular alendronate injection in the treatment of osteoporosis-associated temporomandibular disorders.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral and Maxillofacial Surgery, Second Hospital of Lanzhou University, Lanzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Pathology Department, Medical School, University of Michigan, MI, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: zss_1977@163.com.
authors.forename: S
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D002356:Cartilage / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D007124:Immunoenzyme Techniques; D007270:Injections, Intra-Articular; D007527:Isoenzymes / Q000378:metabolism; D008335:Mandibular Condyle / Q000000981:diagnostic imaging / Q000473:pathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase; D013704:Temporomandibular Joint / Q000000981:diagnostic imaging / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate
keywords: cartilage; drug delivery; osteoporosis; subchondral bone; temporomandibular joint