Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

Abstract

BackgroundThe osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation.ResultsSample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug.ConclusionsThe results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic knees.

Effects of diacerein on cartilage and subchondral bone in early stages of osteoarthritis in a rabbit model

“…The protocol used has been deeply described in a recently published article [19]. Summarising, OA was induced by anterior cruciate ligament transection (ACLT) and partial medial meniscectomy of one knee (randomly chosen) using the contralateral knee as untreated control.…”

“…The gradation of the samples was performed in the same way as in a previously published article [19]…”

“…The evaluated parameters were [19]: Subchondral bone cortical thickness (SB.Th), total cartilage thickness (Cg.Th) and separately non-calcified (nCg.Th) and calcified cartilage thickness (cCg.Th) using the tidemark as reference (Fig. 2a), cartilage surface undulations (FI) (Fig.…”

“…Two scans were performed for each sample, one to assess the microstructure of the subchondral bone and the other to visualise the articular cartilage using previously published parameters [19]. Images were reconstructed based on Feldkamp’s convolution back-projection algorithm [25], and segmented into binary images.…”

Investigational drugs for the treatment of osteoarthritis

“…In an experimental rabbit model of OA, risedronate treatment improved cartilage swelling, superficial fibrillation and the inflammatory changes of joint tissues, as well as modified the orientation of trabeculae lattice [69]. The efficacy of risedronate for the treatment of human OA was investigated in some clinical trials.…”