Early intra-articular injection of alendronate reduces cartilage changes and subchondral bone loss in rat temporomandibular joints after ovariectomy

Int J Oral Maxillofac Surg. 2014 Aug;43(8):996-1004. doi: 10.1016/j.ijom.2014.04.003. Epub 2014 May 6.

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; drug delivery; osteoporosis; subchondral bone; temporomandibular joint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Alendronate / administration & dosage*
  • Animals
  • Cartilage / diagnostic imaging
  • Cartilage / pathology*
  • Female
  • Immunoenzyme Techniques
  • Injections, Intra-Articular
  • Isoenzymes / metabolism
  • Mandibular Condyle / diagnostic imaging
  • Mandibular Condyle / pathology*
  • Ovariectomy*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Tartrate-Resistant Acid Phosphatase
  • Temporomandibular Joint / diagnostic imaging
  • Temporomandibular Joint / pathology*
  • X-Ray Microtomography

Substances

  • Isoenzymes
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Alendronate