Protective Effect of Alendronate on Lumbar Facet Degeneration in Ovariectomized Rats.

BACKGROUND Facet joint degeneration (FJD) is a potential source of lower back pain, and estrogen deficiency can accelerate FJD. The present study aimed to investigate the effects of alendronate (ALN) on FJD induced by ovariectomy (OVX) in rats. MATERIAL AND METHODS Thirty female Sprague-Dawley rats underwent either bilateral OVX (n=20) or sham surgery (n=10). The OVX rats subsequently received either subcutaneous ALN (70 µg/kg/week) or vehicle for 12 weeks. Subchondral bone mass and microarchitecture were evaluated by micro-computed tomography. Cartilage degradation was evaluated by toluidine blue staining and histological scoring. RESULTS Compared with the Sham group, the OVX group had significantly decreased bone mineral density, bone volume/trabecular volume, and trabecular thickness, significantly increased trabecular separation in subchondral bone, and significantly higher histological score for cartilage degeneration, particularly loss of cartilage thickness. ALN treatment significantly reversed the changes in subchondral bone, preserved cartilage thickness, and reduced the histological score. Immunohistochemical analyses showed significantly decreased expression of ADAMTS-4, MMP-13, and caspase-3 in the OVX+ALN group compared with the OVX group. CONCLUSIONS Treatment with ALN suppressed bone loss, subchondral bone architecture deterioration, and cartilage degeneration in OVX rats, which can be explained by roles of ALN in preservation of subchondral bone mass and microarchitecture, and counteraction of catabolism and chondrocyte apoptosis in cartilage.

Salmon calcitonin exerts better preventive effects than celecoxib on lumbar facet joint degeneration and long-term tactile allodynia in rats.

OBJECTIVE: To evaluate and compare the effects of salmon calcitonin (sCT) and celecoxib (CLX) on cartilage, subchondral bone and tactile allodynia in a rat model of lumbar facet joint (FJ) osteoarthritis (OA). METHOD: Forty 3-month-old male Sprague-Dawley rats were randomly divided into four groups: 30 received surgical collagenase (type II) injections in the right L3-L6 facet joints followed by 8 weeks of treatment with normal saline, CLX or sCT, and the other 10 received sham surgery. Tactile allodynia, changes of cartilage and subchondral bone of the L4-L5 FJs, and serum biomarkers were analyzed for all rats. RESULTS: Both sCT and CLX ameliorated cartilage lesions, significantly increased aggrecan expression and decreased caspase-3 expression. sCT also decreased the expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4). According to the micro-computed tomography (micro-CT) analysis, sCT significantly improved microarchitecture parameters of subchondral bone and micro-CT score; and inhibited articular process hypertrophy. CLX showed better antihyperalgesic effects than sCT on days 3 and 7 postoperatively despite no statistical differences, whereas sCT possessed better analgesic effects than CLX on days 42 and 56. Besides, the sCT treatment reduced the elevated cartilage oligomeric matrix protein (COMP) concentration in rats injected with collagenase (type II). CONCLUSIONS: Both sCT and CLX exerted preventive effects on FJ OA caused by collagenase (type II), but sCT showed more protective effects, particularly on maintaining cartilage metabolism, restraining the deterioration of the subchondral bone microarchitecture and tactile allodynia, and reducing serum COMP concentrations.

Salmon Calcitonin Attenuates Degenerative Changes in Cartilage and Subchondral Bone in Lumbar Facet Joint in an Experimental Rat Model.

BACKGROUND Facet joint degeneration (FJD) is one of the common causes of low back pain (LBP), and estrogen deficiency is one of the triggers for FJD. Calcitonin may possess the potential for treating osteoarthritis, but to date the hormone has not been studied in the treatment of FJD. Therefore, the aim of this study was to investigate the effects of salmon calcitonin (sCT) on FJD induced by estrogen deficiency after ovariectomy (OVX). MATERIAL AND METHODS Thirty female Sprague-Dawley rats were randomly assigned to 3 groups: the OVX group received bilateral OVX, the OVX + sCT group received subcutaneous administration of sCT (16 IU/kg/2 days) following bilateral OVX, and the Sham group received sham surgery. All rats were euthanized at 12 weeks post-OVX. Serum COMP level, cartilage degradation, and subchondral bone micro-architecture were evaluated. RESULTS sCT relieved cartilage surface lesions, reduced histological score, and significantly increased cartilage thickness. The OVX + sCT group exhibited significantly increased expression of aggrecan, as well as significantly decreased levels of ADAMTS-4, MMP-13, and caspase-3. The results of micro-computed tomography analysis revealed that the OVX + sCT group exhibited higher BMD, BV/TV, and Tb.Th values but a lower Tb.Sp value than that of the OVX group. Serum COMP concentrations were significantly correlated with histological score and cartilage thickness. CONCLUSIONS sCT can inhibit the progression of FJD in OVX rats, which is attributed to its inhibitory effects on cartilage metabolism imbalance, chondrocyte apoptosis, and subchondral bone remodeling. Serum COMP has diagnostic potential for FJD.