title: Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis.
abstract: To evaluate the effects of alendronate (ALN) on the subchondral bone quality and cartilage degeneration in the early phase of experimental model of osteoarthritis after anterior cruciate ligament transaction (ACLT). Thirty male adult healthy Japanese white rabbits after right ACLT or sham operation were divided into three groups (n = 10 per group): Sham; ACLT + ALN [after ACLT, the rabbits were treated with ALN daily starting from 4 days after surgery (10 μg/kg/d subcutaneously)]; and ACLT + NS group (after ACLT, the rabbits were injected saline as a placebo). At 60 days postsurgery, specimens from the affected knees were harvested. Histological analysis (HE and Safranin-O staining) as well as Mankin score were carried out to assess the cartilage degradation. BMP-2 and MMP-13 immunohistochemistry were also performed to demonstrate the alterations of cartilage molecular metabolism. Subchondral bone quality was evaluated by bone mineral density (BMD) and microstructure histomorphometry assay. For bone mineral density evaluation, 1/4 distal femurs, medial and lateral regions of femoral condylus were scanned with dual X-ray absorptiometry to assess the subchondral bone mass. Giemsa, von Kossa stain, and fluorescence technique for undecalcified bone section were carried out to examine the morphometry of the subchondral trabecular bone and subchondral plate. Histological and Mankin score analyses displayed that ALN treatment markedly reduced cartilage lesions and delayed the cartilage degeneration in OA joints. Immunohistochemistry assay further indicated that this cartilage-protective role of ALN was associated with elevating BMP-2 while inhibiting MMP-13 expression. BMD assessment demonstrated that ALN treatment significantly suppressed subchondral bone resorption. The results from histomorphometry assay of subchondral bone revealed that ALN treatment markedly increased the percent trabecular area (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). Moreover, both thickness and the porosity of the subchondral plate in ACLT + ALN group presented significantly higher than that in ACLT + NS group, while no significant difference was found between ACLT + ALN and Sham group. ALN plays an important role in cartilage protection in OA joints that is associated with the improvement of subchondral bone quality through reduction of subchondral bone resorption. ALN could be potentially used as a disease-modifying strategy to limit the progression of OA.
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China Coal Medical College, Tangshan, Hebei, People's Republic of China. zhliu130@sohu.com
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Hu
authors.forename: Faming
authors.initials: F
authors.lastname: Tian
authors.forename: Huiping
authors.initials: H
authors.lastname: Song
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D015502:Absorptiometry, Photon; D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D001842:Bone and Bones / Q000502:physiology*; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology*; D024043:Collagen Type II / Q000032:analysis; D004195:Disease Models, Animal; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D008853:Microscopy; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology*; D011817:Rabbits
chemical_list: D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D024043:Collagen Type II; D053509:Matrix Metalloproteinase 13; D019386:Alendronate