Rabbit as model for osteoporosis research.

Osteoporosis is a major public health problem affecting more than 200 million people worldwide. The use of different animal models, for the study of its pathophysiology and treatments, is important being actually the ovariectomized rat the most widely used; although this model has several problems due its small size, lack of true closure of epiphyseal plate and bone differences with humans. This review is aimed at summarizing the most common methods published for osteoporosis induction in rabbits as model for human disease with their advantages and disadvantages. The paper shows the advantages of the use of this specie compared with the rat. All the techniques seemed to achieve the osteoporotic condition, but the one which obtained the most consistent bone mineral reduction in less time was the combination of surgery and corticoid treatment. The conclusion of the review was that rabbits are promising as a model of osteoporosis research because of their size, haversian remodelling and closure of epiphyseal plate, which solve some of the problems of the rat model. There are different techniques in the literature used to achieve the osteoporotic condition with diverse results, but there is a lack of consensus as to the best one.

Influence of implant neck surface and placement depth on crestal bone changes and soft tissue dimensions around platform-switched implants: A histologic study in dogs.

OBJECTIVES: To analyse bone remodelling and peri-implant soft tissues around platform-switching implants with and without a machined collar placed at different levels in relation to bone crest. MATERIAL AND METHODS: All mandibular premolars and the first molars were extracted in five dogs. At 6 months, six implants with and without a machined neck (MACH and GBAE implants, respectively) were randomly inserted in each hemimandible positioning the implant-abutment interface in either a supracrestal (+1.5 mm), equicrestal, or subcrestal (-1.5 mm) position. After 6 months, animals were killed for histomorphometric analysis. RESULTS: When net bone loss (primary outcome variable) was compared between MACH and GBAE groups, the multivariable regression analysis revealed no significant differences between implants inserted at the same vertical position. The dimensions of the peri-implant mucosa were greater in MACH implants compared with GBAE implants; however, these differences failed to reach statistical significance. Regarding the number of inflammatory cells and collagen fibre orientation, no statistically significant differences were found between MACH and GBAE groups. CONCLUSIONS: The surface treatment of the implant neck does not seem to have an influence on net bone loss, and there were no statistically significant differences in the peri-implant soft tissues between platform-switching implants with and without a machined neck.

A novel methodological approach using superimposed Micro-CT and STL images to analyze hard and soft tissue volume in immediate and delayed implants with different cervical designs.

OBJECTIVES: To study the hard and soft tissue volume after placing immediate (IMI) or delayed implants (DLI) with a triangular coronal macro-design (Test/T) or a conventional cylindrical design (Control/C). MATERIAL AND METHODS: T/C implants were inserted in healed ridges or in fresh extraction sockets of eight beagle dogs. Biopsies were processed for Micro-CT analysis and dental stone casts were optically scanned to obtain STL files revealing the soft tissue contours at 12 weeks. Image analysis software was utilized to match common landmarks superimposing the two sets of data. Three distinct volumes were calculated; buccal bone volume (B-BV), soft tissue volume below the implant shoulder (EC-STV), and the soft tissue volume above the implant shoulder (SC-STV). Using linear measurements, the soft tissue height (STH), the mucosal thickness (MT-IS), and the distance from the implant shoulder to the bone crest (I-BC) were assessed in the digital images and in conventional histology to assess the concordance, reproducibility, and reliability. RESULTS: There were no significant differences between test and control implants regarding the buccal bone volume, although test implants had greater B-BV in all locations except for PM2. The soft tissue volume was similar at T/C implants. The surgical approach influenced the distribution of the total tissue volume. In the IMI, a low position of the bone crest was correlated with low values of B-BV, SC-STV, MT-IS, and STH. Linear measurements showed a high correlation between the histology and digital measurements and high inter and intra examiner agreement. CONCLUSION: The superimposition of Micro-CT/STL allowed the analysis of soft and hard tissue volumes. Reduction of the implant buccal aspect resulted in nonsignificant higher bone volume although similar soft tissue volume while the surgical approach influenced soft tissue response.

Hard and soft tissue integration of immediate and delayed implants with a modified coronal macrodesign: Histological, micro-CT and volumetric soft tissue changes from a pre-clinical in vivo study.

AIM: To study the healing of peri-implant tissues around implants with a triangular coronal third (test) or cylindrical (control). MATERIALS AND METHODS: In eight beagle dogs, immediate and delayed implants were placed. Test and control implants were randomly assigned and the hard and soft tissue healing was evaluated with histology and micro-CT analysis at 4 and 12 weeks. The soft tissue contour changes were assessed by image analysis software. RESULTS: When measured at the implant shoulder level, the buccal crestal width (primary outcome assessed in mm) attained similar values in test and control implants. More apically (3 mm) test implants had greater buccal crestal width in delayed and immediate sites. For vertical soft and hard tissue measurements, no significant differences were found between Test and Control. Micro-CT evaluation of the buccal volume of interest showed less volume of implant component in T implants in all sites, although bone volume was not significantly different between T/C. Soft tissue contours were similar around T/C implants. CONCLUSION: Triangular implants showed similar percentage of osseointegration, buccal bone volume and soft tissue contours, although attaining greater buccal crestal bone width. No differences were found in regard to soft tissue dimensions and the position of the first bone-to-implant contact.

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases.

Melatonin is a hormone synthesised and secreted by the pineal gland and other organs. Its secretion, controlled by an endogenous circadian cycle, has been proven to exert immunological, anti-oxidant, and anti-inflammatory effects that can be beneficial in the treatment of certain dental diseases. This article is aimed at carrying out a review of the literature published about the use of melatonin in the dental field and summarising its potential effects. In this review article, an extensive search in different databases of scientific journals was performed with the objective of summarising all of the information published on melatonin use in dental diseases, focussing on periodontal diseases and dental implantology. Melatonin released in a natural way into the saliva, or added as an external treatment, may have important implications for dental disorders, such as periodontal disease, as well as in the osseointegration of dental implants, due to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated to have beneficial effects on dental pathologies, although further research is needed to understand the exact mechanisms of this molecule.

Mechanical and chemical implant decontamination in surgical peri-implantitis treatment: preclinical "in vivo" study.

OBJECTIVE: The aim of the present study was to evaluate the effect of a titanium brush and chemical agents following surgical treatment of experimental peri-implantitis. MATERIAL AND METHODS: Six implants were installed in the mandible of eight beagle dogs (unit of analysis) 3 months after tooth extraction. Experimental peri-implantitis was induced 3 months later. The defects were randomly allocated in three treatment groups: (a) TiBrush(™)  + sodium hypochlorite + chlorhexidine (TBH), (b) TiBrush(™)  + chlorhexidine (TB), (c) an ultrasonic device + chlorhexidine (US). The distal implant in each hemimandible was used as control, and no treatment was done. Clinical and histological measurements were performed after 3 months of healing. RESULTS: All treatment procedures resulted in statistically significant improvements of all clinical parameters. Histomorphometrical analysis revealed no statistically significant differences between treatment groups in terms of woven bone height (primary outcome). However, there were differences between test and control groups in terms of inflammation, bone defect depth and bone refill without differences between TBH and TB groups. CONCLUSIONS: Resolution of peri-implantitis after access surgery and decontamination of peri-implant surfaces with TiBrush(™) with or without sodium hypochlorite is possible. However, the concomitant use of sodium hypochlorite has minor effect on treatment outcomes.

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

BACKGROUND: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans. At present, there is no ideal treatment option. The aim of this study was to assess the effects of the treatment with oral diacerein on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of osteoarthritis by micro-CT evaluation and histological analysis. To this purpose, osteoarthritis was surgically induced on one knee of 16 rabbits using the contralateral knee as healthy controls. Treatment was started three weeks later and lasted eight weeks. Animals were divided into two groups for treatment: Placebo (treated daily with oral saline) and diacerein (treated orally with 1.5 mg/kg/day of diacerein). RESULTS: Sample analysis revealed that this model induced osteoarthritis in the operated knee joint. Osteoarthritis placebo group showed a significant increase in non-calcified cartilage thickness and volume with respect to the control placebo group and important changes in the synovial membrane; whereas the parameters measured in subchondral bone remained unchanged. In the osteoarthritis diacerein-treated group the results showed an improvement with respect to the OA placebo group in all parameters, although the results were not statistically significant. CONCLUSION: The results of this animal study suggested that the diacerein treatment for OA may be able to ameliorate the swelling and surface alterations of the cartilage and exert an anti-inflammatory effect on the synovial membrane, which might contribute to OA improvement, as well as an anabolic effect on subchondral trabecular bone.

Soft tissue histomorphology at implants with a transmucosal modified surface. A study in minipigs.

OBJECTIVES: To investigate soft tissue histomorphology and quality around implants with a modified transgingival collar surface comparatively to a machined. MATERIAL AND METHODS: Twenty-seven Straumann Standard Tissue Level implants belonging to the following groups (nine of each group): Ti modSLA with machined collar (Ti-M), Ti modSLA with machined, acid-etched surface collar (Ti-modMA), and TiZr modSLA with machined, acid-etched surface collar (TiZr-modMA) were placed in the mandible of six minipigs. After 8 weeks of healing, buccal sections were obtained and processed for histological evaluation. RESULTS: Histometric soft tissue outcomes were similar for the three types of implants. The percentage of connective tissue attached to implant surface and its length was longer at TiZr-modMA with respect to Ti-M implants. The number of inflammatory cells was slightly higher at the TiZr-modMA with respect to Ti-M implant. The percentage of area occupied by perpendicular collagen fibers was slightly higher for the modified surfaces in comparison with the machined. CONCLUSIONS: Modified implant collar surfaces at Ti and TiZr implants showed a soft tissue interface similar to machined. A tendency of increasing number of perpendicular collagen fibers and improved connective tissue contact was found at the modified implant surfaces.

Comparison of various SYSADOA for the osteoarthritis treatment: an experimental study in rabbits.

BACKGROUND: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans and its treatment is a major orthopaedic challenge because there is no ideal drug treatment to preserve joint structure and function, as well as to ameliorate the symptomatology of the disease. The aim of the present study was to assess, using histology, histomorphometry and micro-CT, the effects of the treatment with several drugs of the SYSADOA group and a bisphosphonate in a model of early osteoarthritis, comparing all the results obtained. METHODS: Osteoarthritis was surgically induced by anterior cruciate ligament transection and partial meniscectomy on one knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8 weeks; at the end of this period, the animals were sacrificed. Animals were divided into seven groups (8 animals each), one for each regimen of treatment (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein, risedronate and a combination of risedronate and glucosamine) and one for the control (placebo-treated) group. Following sacrifice, femoral osteochondral cylinders and synovial membrane samples were obtained for their evaluation by qualitative and quantitative histology and micro-CT. RESULTS: The model induced osteoarthritic changes in the knee joints and none of the treatments showed a significantly better efficacy over the others. Regarding cartilage thickness and volume, all the treatments achieved scores halfway between control groups, without statistical differences. Regarding the synovial membrane, diacerein and risedronate showed the best anti-inflammatory profile, whereas glucosamine and chondroitin did not present any effect standing the hyaluronic acid results between the others. Regarding the subchondral bone, there were no differences in thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to have considerably modified the orientation of the trabecular lattice. CONCLUSIONS: Out of the different drugs evaluated in the study for OA treatment, diacerein and risedronate showed, in all the parameters measured, a better profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and promoted bone formation, but with a poor synovial effect; and finally, chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way to the others, but had no effect on cartilage surface, synovial membrane or subchondral bone.

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

BACKGROUND: The 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. RESULTS: Sample 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. CONCLUSIONS: The 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.

In vivo assessment of marine vs bovine origin collagen-based composite scaffolds promoting bone regeneration in a New Zealand rabbit model.

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic. The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.

Platelet-derived extracellular vesicles formulated with hyaluronic acid gels for application at the bone-implant interface: An animal study.

Background/Objective: Platelet derived extracellular vesicles (pEV) are promising therapeutical tools for bone healing applications. In fact, several in vitro studies have already demonstrated the efficacy of Extracellular Vesicles (EV) in promoting bone regeneration and repair in various orthopedic models. Therefore, to evaluate the translational potential in this field, an in vivo study was performed. Methods: Here, we used hyaluronic acid (HA) gels formulated with pEVs, as a way to directly apply pEVs and retain them at the bone defect. In this study, pEVs were isolated from Platelet Lysate (PL) through size exclusion chromatography and used to formulate 2% HA gels. Then, the gels were locally applied on the tibia cortical bone defect of New Zeland White rabbits before the surgical implantation of coin-shaped titanium implants. After eight weeks, the bone healing process was analyzed through biomechanical, micro-CT, histological and biochemical analysis. Results: Although no biomechanical differences were observed between pEV formulated gels and non-formulated gels, biochemical markers of the wound fluid at the interface presented a decrease in Lactate dehydrogenase (LDH) activity and alkaline phosphatase (ALP) activity for pEV HA treated implants. Moreover, histological analyses showed that none of the treatments induced an irritative effect and, a decrease in the fibrotic response surrounding the implant for pEV HA treated implants was described. Conclusion: In conclusion, pEVs improve titanium implants biocompatibility at the bone-implant interface, decreasing the necrotic effects of the surgery and diminishing the fibrotic layer associated to the implant encapsulation that can lead to implant failure.

Bisphosphonates as disease-modifying drugs in osteoarthritis preclinical studies: a systematic review from 2000 to 2020.

Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a great heterogeneity. Therefore, the aim of this study is to systematically review the main effects of bisphosphonate use on synovial joint tissues and biochemical markers in preclinical studies over the past two decades (2000-2020). Three databases (Pubmed, Scopus, and Web of Science) were searched, and after screening, twenty-six studies with five different types of bisphosphonates were included in the review. The animal model selected, the type of bisphosphonate used, the therapy duration, and the main effects of individual drugs on synovial tissues were evaluated. Additionally, the quality and risk of bias assessments were performed using the Animals in Research Reporting In Vivo Experiments guidelines and the Systematic Review Centre for Laboratory animal Experimentation tool. Studies showed high variability in experimental designs. Consequently, the comparison of the findings in order to draw specific conclusions about the effectiveness of the drugs is complicated. However, the results of this systematic review suggested that bisphosphonates seemed to reduce the osteoarthritic changes in a dose-dependent manner showing better chondroprotective effects at high doses. Besides, a time-dependent efficacy was also detected in terms of cartilage status. One can conclude that the disease stage of the time-point of treatment initiation may constitute a key factor in the antiresorptive drug efficacy. Generally, we noted that bisphosphonate administration seemed to show positive subchondral bone conservation and fewer biomarker alterations. However, they did not appear to suppress the osteophyte development and their chondroprotective effect is highly variable among the studies. Bisphosphonates appeared to show a positive anti-inflammatory effect on the synovial membrane. However, only a few included publications were focused on their investigation. Regarding the therapy duration, there is a significant lack of evidence on evaluating their effectiveness in preclinical long-term studies and further experimental studies may be needed to examine the pharmacological response in these circumstances. This systematic review might help to clarify the efficacy of bisphosphonates and their function as disease-modifying treatments in osteoarthritis.

Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021.

Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.

Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model.

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

A randomized controlled preclinical trial on 3 interposal temporomandibular joint disc implants: TEMPOJIMS-Phase 2.

The effort to develop an effective and safe temporomandibular joint (TMJ) disc substitute has been one of the mainstreams of tissue engineering. Biodegradable customized scaffolds could approach safety and effectiveness to regenerate a new autologous disc, rather than using non-biodegradable materials. However, it is still technically challenging to mimic the biomechanical properties of the native disc with biodegradable polymers. In this study, new 3D tailored TMJ disc implants were developed: (1) Poly(glycerol sebacate) (PGS) scaffold reinforced with electrospun Poly(εcaprolactone) (PCL) fibers on the outer surface (PGS+PCL); (2) PCL and polyethylene glycol diacrylate (PEGDA) (PCL+PEGDA); and (3) PCL. The TMJ implants were tested in a randomized preclinical trial, conducted in 24 black Merino sheep TMJ, perfoming bilateral interventions. Histologic, imaging, and kinematics analysis was performed. No statistical changes were observed between the PGS+PCL disc and the control group. The PCL+PEGDA and PCL groups were associated with statistical changes in histology (p = 0.004 for articular cartilage mid-layer; p = 0.019 for structure changes and p = 0.017 for cell shape changes), imaging (p = 0.027 for global appreciation) and dangerous material fragmentation was observed. No biomaterial particles were observed in the multi-organ analysis in the different groups. The sheep confirmed to be a relevant animal model for TMJ disc surgery and regenerative approaches. The PCL and PCL+PEGDA discs presented a higher risk to increase degenerative changes, due to material fragmentation. None of the tested discs regenerate a new autologous disc, however, PGS+PCL was safe, demonstrated rapid resorption, and was capable to prevent condyle degenerative changes.

No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups (n = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.