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Early intra-articular injection of alendronate reduces cartilage changes and subchondral bone loss in rat temporomandibular joints after ovariectomy
Affiliation:1. CNR Institute of Neuroscience, Viale G. Colombo 3, Padova, Italy;2. Department of Molecular Medicine, University of Padova, Via Marzolo 3, Padova, Italy;3. Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, Padova, Italy
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.
Keywords:cartilage  subchondral bone  temporomandibular joint  osteoporosis  drug delivery
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