Osteophytes, juxta-articular radiolucencies and cancellous bone changes in the proximal tibia of patients with knee osteoarthritis

OBJECTIVE: To determine differences in tibial cancellous bone organisation in knee osteoarthritis (OA) between the central weight-bearing region and juxta-articular radiolucencies adjacent to small, medium or large marginal osteophytes. METHODS: Patients with medial compartment OA (n = 60; F = 39), mean (SD) age 60.0 (9.7) years, and non-OA reference subjects (n = 21; F = 5), mean (SD) age 36.8 (11.5) years, had x4 macroradiographs digitised by laser scanner. Using a modified Osteoarthritis Research Society (OARS) Atlas, right and/or left knees were graded according to marginal osteophyte size into those with small (n = 30), medium (n = 30) or large (n = 27) marginal osteophytes, identified as OPH1, OPH2 and OPH3, respectively. Non-OA knees (n = 30) were anatomically normal. Computerised method of Fractal Signature Analysis (FSA) quantified differences in cancellous bone structure between non-OA and osteophyte subgroups at two regions of interest (ROIs); central weight-bearing and tibial margin. RESULTS: Compared to non-OA, vertical trabecular number increased significantly (P < 0.05) in all osteophyte subgroups (width range 0.12-1.14 mm) within both ROIs. In OPH3, this increase was significantly (P < 0.05) greater compared to OPH2 in the central ROI, and to OPH2 and OPH1 in the marginal ROI at most trabecular widths (0.12-1.14 mm). In the marginal ROI, compared to non-OA, horizontal trabeculae number decreased in all osteophyte subgroups. This decrease was significantly greater in OPH3 compared to OPH2 and OPH1 at small to medium trabecular widths (0.12-0.54 mm). CONCLUSION: Compared to disease associated bone loss at the central ROI of the tibia, the extent of juxta-articular bone loss appears to be associated with the size of the marginal osteophytes.     

Osteochondral autografts transfer for post-traumatic osteochondral defect of the knee-2 to 5 years follow-up

The treatment of post-traumatic osteochondral defects of the weight-bearing surface of the knee in young active patients remains a significant challenge. We report the results of an osteochondral autograft transfer (OAT) in 18 patients (mean age 29 years) with post-traumatic focal osteochondral defects of the knee. Sixteen lesions were over the femoral condyle and two were over the tibial plateau. The average size of the lesion was 4.1 cm² (from 2.25 to 6 cm²), and the subchondral bone involved no more than 1 cm in depth. Osteochondral grafts were harvested from the non-weight-bearing area of the femoral condyle. Ten patients also had concomitant surgical procedures. The average follow-up was 42 months (from 24 to 64 months). All patients were evaluated by Lysholm and Tegner activity scores and plain radiographs. Nine patients had MRI, eight patients had second-look arthroscopy and two had a biopsy. Sixteen patients (89%) had good to excellent results, while two patients with lesion over the tibial surface had fair results. The biopsy revealed survival of hyaline cartilage. For small to medium osteochondral lesion over the femoral condyle of the knee in selected patients, osteochondral autografting yielded promising short to mid-term results.     

Tibial subchondral bone size and knee cartilage defects: relevance to knee osteoarthritis

Unlike knee plain radiography which can only detect joint space narrowing and osteophytes, magnetic resonance imaging can directly visualize and analyse the whole knee structure, including bone size, cartilage defects and loss of cartilage volume. Tibial subchondral bone area expansion may be primary and is associated with risk factors such as age, body mass index (BMI), genetics and/or limb malalignment. It can lead to the development of knee defects, which may also be caused by demographic, anthropometric and environmental factors such as age, female sex, BMI and smoking as well as structural changes such as osteophytes, bone marrow lesions, meniscal tears, meniscal extrusion and ligament abnormalities. Once knee cartilage defects develop, they have a variable natural history but are associated with subsequent cartilage loss in a dose-response manner. Both tibial subchondral bone area and knee cartilage defects are quantitatively related to the severity of knee osteoarthritis (OA), and predictive of the need for knee joint replacement in subjects with knee OA independent of radiographic change. Taken as a whole, these studies suggest that tibial subchondral bone expansion and cartilage defect development represent important targets for the prevention of cartilage loss and joint replacement.     

Influence of age and gender on microarchitecture and bone remodeling in subchondral bone of the osteoarthritic femoral head

IntroductionAge and gender have been reported to have a remarkable impact on bone homeostasis. However, subchondral bone, which plays a pivotal role in the initiation and progression of OA, has been poorly investigated. This study was to investigate age- and gender-related changes of microarchitecture and bone remodeling in subchondral bone in OA.MethodsSubchondral trabecular bone (STB) and deeper trabecular bone (DTB) specimens were extracted in the load-bearing region of femoral heads from 110 patients with OA. Micro-CT and histomorphometry were performed to analyze microarchitectural and bone remodeling changes of all specimens.ResultsCompared to DTB, STB showed more sclerotic microarchitecture, more active bone remodeling and higher frequency of bone cysts. There were no gender differences for both microarchitecture and bone remodeling in STB. However, gender differences were found in DTB, with thinner Tb.Th, higher Tb.N, higher OS/BV and ES/BV in males. In both STB and DTB, no correlation between microarchitecture and age was found in both genders. However, bone remodeling of STB increased significantly with age in males, while bone remodeling of DTB increased significantly with age in females. No age or gender preference was found in subchondral bone cyst (SBC) frequency. The cyst volume fraction was correlated with neither age nor gender.ConclusionsThere were differences in microarchitecture and bone remodeling between STB and DTB, which may be due to the distinct biomechanical and biochemical functions of these two bone structures in maintaining joint homeostasis. OA changed the normal age- and gender-dependence of bone homeostasis in joints, in a site-specific manner.     

Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.     

High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis

OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes. RESULTS: MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies.     

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs).Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.     

膝关节原发性骨关节炎软骨和软骨下骨病理改变的定量研究

目的观察膝关节原发性骨关节炎(osteoarthritis,OA)胫骨平台软骨和软骨下骨病理改变特点,对比内、外侧平台软骨和软骨下骨结构参数,探讨钙化层和软骨下骨在OA发病机制中的作用。方法取2009年10月-2011年5月行人工全膝关节置换术治疗的30例30膝原发性OA患者自愿捐赠的新鲜胫骨平台标本进行实验。其中男11例,女19例;年龄55～78岁,平均65.1岁。病程10～25年,平均16.6年;患膝内翻畸形1～23°,平均9.3°。大体观察胫骨平台后在内、外侧中央负重区取材,常规制备脱钙石蜡切片,行HE和番红O/固绿染色,观察关节软骨退变特点,参照Mankin评分标准评分并分期;观察钙化层及软骨下骨病理改变。应用Image Pro Plus 6.0图像分析软件测量软骨和软骨下骨结构参数,包括软骨全层(total articular cartilage,TAC)厚度、钙化层(articular calcified cartilage,ACC)厚度、ACC/TAC比值、软骨下骨板(subchondral bone plate,SCP)厚度以及骨小梁体积分数(trabecular bone volume,BV/TV)。结果大体观察内侧平台软骨退变较外侧严重,内侧平台软骨Mankin评分为(12.4±1.1)分,显著高于外侧平台的(8.3±1.6)分(t=12.173,P=0.000)。根据Mankin评分结果在60个标本中,14个为OA早期,可见软骨浅表层裂隙、潮线复制和软骨下骨增厚;19个为OA中期,可见软骨深层裂隙、多发软骨下骨吸收陷窝和明显增厚的软骨下骨;27个为OA晚期,可见软骨全层缺失、软骨内化骨和"象牙化"软骨下骨。软骨和软骨下骨结构参数测定示:内侧平台TAC厚度显著低于外侧平台,ACC/TAC比值、BV/TV及SCP厚度显著高于外侧平台,差异均有统计学意义(P<0.05)。内、外侧平台ACC厚度比较,差异无统计学意义(P>0.05)。结论钙化层和软骨下骨可能在OA发生与进展中发挥了重要作用。     

Effects of long-term estrogen replacement therapy on the prevalence and area of periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

Osteoarthritis (OA) occurs naturally in cynomolgus macaques. The purposes of the present study were to: 1) develop histological measurement schemes to measure the cross-sectional area of axial and abaxial osteophytes in the proximal tibia; 2) determine the effects of long-term estrogen replacement therapy (ERT) on osteophyte prevalence and area; and 3) assess relationships between osteophyte size and risk factors of OA (age and body weight) and concurrent bone and cartilage lesions. Adult female cynomolgus macaques (n=180) were bilaterally ovariectomized (OVX) and were treated for 3 years with ERT, soy phytoestrogens (SPE), or no hormones (OVX controls). At necropsy, the prevalence and cross-sectional area of periarticular tibial osteophytes were evaluated histologically. Treatment effects on osteophyte prevalence and area were evaluated using Chi-square analyses and Kruskal-Wallis test, respectively; other comparisons were evaluated using regression analyses. The prevalence of abaxial osteophytes in the medial tibial plateau was not significantly affected by treatment group; however, the prevalence of abaxial osteophytes in the lateral tibial plateau was significantly lower in ERT group than SPE group (p<0.01). The total number of abaxial osteophytes (sum of lateral and medial) was significantly lower in ERT group compared to OVX and SPE groups. Neither the prevalence of axial osteophytes nor the sum of lateral and medial axial osteophytes was significantly affected by treatment in either tibial plateau. There were no significant treatment effects on axial or abaxial osteophyte cross-sectional area in either tibial plateau. There was a significant positive correlation between abaxial osteophyte area and SCB thickness in the medial tibial plateau (p=0.048); however, there were no significant correlations between abaxial osteophyte area (medial or lateral) and age or body weight. In this model of naturally occurring OA, long-term ERT does not consistently reduce the prevalence, and has no significant effects on cross-sectional area, of periarticular tibial osteophytes.     

Knee Images Digital Analysis (KIDA): a novel method to quantify individual radiographic features of knee osteoarthritis in detail

OBJECTIVE: Radiography is still the golden standard for imaging features of osteoarthritis (OA), such as joint space narrowing, subchondral sclerosis, and osteophyte formation. Objective assessment, however, remains difficult. The goal of the present study was to evaluate a novel digital method to analyse standard knee radiographs. METHODS: Standardized radiographs of 20 healthy and 55 OA knees were taken in general practise according to the semi-flexed method by Buckland-Wright. Joint Space Width (JSW), osteophyte area, subchondral bone density, joint angle, and tibial eminence height were measured as continuous variables using newly developed Knee Images Digital Analysis (KIDA) software on a standard PC. Two observers evaluated the radiographs twice, each on two different occasions. The observers were blinded to the source of the radiographs and to their previous measurements. Statistical analysis to compare measurements within and between observers was performed according to Bland and Altman. Correlations between KIDA data and Kellgren & Lawrence (K&L) grade were calculated and data of healthy knees were compared to those of OA knees. RESULTS: Intra- and inter-observer variations for measurement of JSW, subchondral bone density, osteophytes, tibial eminence, and joint angle were small. Significant correlations were found between KIDA parameters and K&L grade. Furthermore, significant differences were found between healthy and OA knees. CONCLUSION: In addition to JSW measurement, objective evaluation of osteophyte formation and subchondral bone density is possible on standard radiographs. The measured differences between OA and healthy individuals suggest that KIDA allows detection of changes in time, although sensitivity to change has to be demonstrated in long-term follow-up studies.     

骨关节炎软骨下骨研究进展

骨关节炎是最常见的关节疾病,其病理以关节软骨退变、软骨下骨硬化与骨赘形成为特点。目前骨关节炎的始发病理尚不明确,既往许多研究聚焦于关节软骨并认为软骨下骨的改变继发于关节软骨的退变;然而近年研究报道关节软骨下骨低骨密度,尤其是膝骨关节炎的软骨下骨,软骨下骨呈高转换,以及骨吸收抑制剂治疗骨关节炎有效,都提示软骨下骨在骨关节炎的病理机制中具有重要地位。本文就骨关节炎软骨下骨的研究进展做一综述。     

Arthroscopic osteochondral autograft transplantation for chondral lesion of the tibial plateau of the knee

Arthroscopic osteochondral autograft transplantation is often used to treat chondral/osteochondral lesions of the femoral condyle of the knee. However, arthroscopic autologous osteochondral grafting to the tibial plateau has not been reported. We report the surgical technique and the clinical course of a patient who underwent engraftment by this method. A 26-year-old man developed symptoms of pain and catching in his knee. Arthroscopy revealed a deep chondral lesion, 10 × 15 mm in size, down to the subchondral bone on the posterocentral area of the lateral tibial plateau. The injured cartilage was debrided using a curette and an abrader until normal healthy cartilage bordered the debrided defect. An osteochondral plug, 10 mm in diameter and 20 mm long, the chondral surface of which was orientated 25° obliquely, was harvested from the most peripheral and proximal part of the lateral patellar groove. A bony hole was created in the center of the defect through the tibia using a core reamer. The osteochondral plug was inserted from the tibial window through the bony hole. To enhance the stability of the osteochondral fragment, bioactive ceramic fillers were used to fill the space below the plug. A second-look arthroscopy 10 months after surgery showed that the grafted osteochondral plug was well adapted and integrated into the surrounding cartilage on the lateral tibial plateau.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 6 (July-August), 2001: pp 653–659     

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Type 2 diabetes(T2 D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile,abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis(OA).Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2 D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic(n = 70) and diabetes(n = 51) groups. Tibial plateaus were also collected from cadaver donors(n = 20) and used as controls.Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase(TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International(OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~+ osteoclasts and lower number of Osterix~+ osteoprogenitors and Osteocalcin~+ osteoblasts. T2 D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2 D-associated knee OA.     

The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse

OBJECTIVE: To evaluate anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgical instability models of osteoarthritis (OA) in the 129/SvEv mouse knee joint. DESIGN: Micro-surgical techniques were used to perform ACLT or DMM under direct visualization. Histological scoring was performed on multiple sections to assess cartilage damage across the entire joint. RESULTS: The ACLT model gave severe OA, chondrogenesis of the joint capsule and, in some cases, severe subchondral erosion of the posterior tibial plateau. Surgical DMM was less invasive than the ACLT procedure and resulted in lesions primarily on the central weight-bearing region of the medial tibial plateau and medial femoral condyles. Lesions in the DMM model progressed from mild-to-moderate OA at 4 weeks, to moderate-to-severe OA at 8 weeks post-surgery. Destruction of the subchondral bone was never observed in the DMM model. CONCLUSIONS: ACLT is not recommended in the mouse due to the high surgical proficiency required and the development of severe OA that may involve subchondral bone erosion. The severity and location of lesions following DMM are consistent with lesions observed in aged spontaneous mouse models of OA. The DMM model has sufficient sensitivity to show disease modification, as observed with the ADAMTS-5 knock out (KO) mouse. The DMM model should be a first choice to challenge mice with gene deletions of potential targets in OA.     

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro–computed tomography and micro–finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.     

Systematic mapping of the subchondral bone 3D microarchitecture in the human tibial plateau: Variations with joint alignment

Tibial subchondral bone plays an important role in knee osteoarthritis (OA). Microarchitectural characterization of subchondral bone plate (SBP), underlying subchondral trabecular bone (STB) and relationships between these compartments, however, is limited. The aim of this study was to characterize the spatial distribution of SBP thickness, SBP porosity and STB microarchitecture, and relationships among them, in OA tibiae of varying joint alignment. Twenty‐five tibial plateaus from end‐stage knee‐OA patients, with varus (n = 17) or non‐varus (n = 8) alignment were micro‐CT scanned (17 μm/voxel). SBP and STB microarchitecture was quantified via a systematic mapping in 22 volumes of interest per knee (11 medial, 11 lateral). Significant within‐condylar and between‐condylar (medial vs. lateral) differences (p < 0.05) were found. In varus, STB bone volume fraction (BV/TV) was consistently high throughout the medial condyle, whereas in non‐varus, medially, it was more heterogeneously distributed. Regions of high SBP thickness were co‐located with regions of high STB BV/TV underneath. In varus, BV/TV was significantly higher medially than laterally, however, not so in non‐varus. Moreover, region‐specific significant associations between the SBP thickness and SBP porosity and the underlying STB microarchitecture were detected, which in general were not captured when considering the values averaged for each condyle. As subchondral bone changes reflect responses to local mechanical and biochemical factors within the joint, our results suggest that joint alignment influences both the medial‐to‐lateral and the within‐condyle distribution of force across the tibia, generating corresponding local bony responses (adaptation) of both the subchondral bone plate and underlying subchondral trabecular bone microarchitecture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1927–1941, 2017.

     

Raman spectroscopy detection of molecular changes associated with two experimental models of osteoarthritis in rats

The aim of the present study was to evaluate the feasibility of applying Raman spectroscopy in probing the molecular changes in terms of collagen deposition and tissue remodeling associated with two well-established experimental models of osteoarthritis (OA) in knee of rats. In order to evaluate alterations in the articular surface area, the menisci-covered tibial region was assessed into three groups as follows: control (joint preserved) and two models of experimental knee OA: collagenase-induced model (n?=?8) and treadmill exercise-induced model (n?=?8). Each group was examined for molecular changes using spectral parameters related to cartilage, subchondral bone, and bone tissues. A significant increase of Raman ratios related to mineralization and tissue remodeling was found (p?<?0.05), suggesting that both models were successful for inducing OA in rats. The significantly lower phenylalanine content and higher crystallinity in the treadmill exercise-induced model of OA than collagenase-induced model of OA (p?<?0.05) indicated that the OA pathogenesis was model-dependent. Thus, this work suggests that the Raman spectroscopy technique has potential for the diagnosis and detection of cartilage damage and monitoring of subchondral bone and bone in OA pathogenesis at the molecular level.     

Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis

During osteoarthritis (OA), angiogenesis is increased in the synovium, osteophytes and menisci and leads to ossification in osteophytes and the deep layers of articular cartilage. Angiogenic and antiangiogenic factors might both be upregulated in the osteoarthritic joint; however, vascular growth predominates, and the articular cartilage loses its resistance to vascularization. In addition, blood vessel growth is increased at--and disrupts--the osteochondral junction. Angiogenesis in this location is dependent on the creation of channels from subchondral bone spaces into noncalcified articular cartilage. Inflammation drives synovial angiogenesis through macrophage activation. Blood vessel and nerve growth are linked by common pathways that involve the release of proangiogenic factors, such as vascular endothelial growth factor, β-nerve growth factor and neuropeptides. Proangiogenic factors might also stimulate nerve growth, and molecules produced by vascular cells could both stimulate and guide nerve growth. As sensory nerves grow along new blood vessels in osteoarthritic joints, they eventually penetrate noncalcified articular cartilage, osteophytes and the inner regions of menisci. Angiogenesis could, therefore, contribute to structural damage and pain in OA and provide potential targets for new treatments.     

Early inhibition of subchondral bone remodeling slows load-induced posttraumatic osteoarthritis development in mice

Posttraumatic osteoarthritis (PTOA) is associated with abnormal and increased subchondral bone remodeling. Inhibiting altered remodeling immediately following joint damage can slow PTOA progression. Clinically, however, inhibiting remodeling when significant joint damage is already present has minimal effects in slowing further disease progression. We sought to determine the treatment window following PTOA initiation in which inhibiting remodeling can attenuate progression of joint damage. We hypothesized that the most effective treatment would be to inhibit remodeling immediately after PTOA initiation. We used an animal model in which a single bout of mechanical loading was applied to the left tibia of 26-week-old male C57Bl/6 mice at a peak load of 9 N to initiate load-induced PTOA development. Following loading, we inhibited bone remodeling using daily alendronate (ALN) treatment administered either immediately or with 1 or 2 weeks' delay up to 3 or 6 weeks post-loading. A vehicle (VEH) treatment group controlled for daily injections. Cartilage and subchondral bone morphology and osteophyte development were analyzed and compared among treatment groups. Inhibiting remodeling using ALN immediately after load-induced PTOA initiation reduced cartilage degeneration, slowed osteophyte formation, and preserved subchondral bone volume compared to VEH treatment. Delaying the inhibition of bone remodeling at 1 or 2 weeks similarly attenuated cartilage degeneration at 6 weeks, but did not slow the development of osteoarthritis (OA)-related changes in the subchondral bone, including osteophyte formation and subchondral bone erosions. Immediate inhibition of subchondral bone remodeling was most effective in slowing PTOA progression across the entire joint, indicating that abnormal bone remodeling within the first week following PTOA initiation played a critical role in subsequent cartilage damage, subchondral bone changes, and overall joint degeneration. These results highlight the potential of anti-resorptive drugs as preemptive therapies for limiting PTOA development after joint injury, rather than as disease-modifying therapies after joint damage is established. © 2021 American Society for Bone and Mineral Research (ASBMR).