Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis

OBJECTIVE: To systematically study the histopathology of sacroiliitis in ankylosing spondylitis (AS) at 5 different stages of the disease. METHODS: Two independent observers assessed 75 microscopic features in the sacroiliac (SI) joints in 12 cases of AS (5 biopsies, 7 autopsies) and in 22 control cases (all autopsies). RESULTS: In AS, synovitis, pannus formation, myxoid marrow, superficial cartilage destruction, enthesitis, intraarticular fibrous strands, new bone formation, and bony ankylosis were significantly more frequent than in control cases, in which there was more endochondral bone within deep-zone articular cartilage. Cartilaginous fusion occurred in both groups, but much earlier in AS. There was no residual synovium when the joint lumen was totally occluded. Mild but destructive synovitis and myxoid subchondral bone marrow were the earliest changes identified in AS. These lesions destroyed the adjacent articular tissues, a loss that was followed to varying degrees by fibrous scarring, woven bone, and new cartilage. The original cartilages also fused, and chondral fusion was the predominant mode of ankylosis. Both the original and the reparative cartilaginous tissues were replaced by bone. Active enthesitis occurred in 2 advanced and 3 late cases; fibrous scar tissue, presumed to represent previous enthesitis, was observed in all stages except the earliest. Paraarticular bone was at first dense, and later porotic. CONCLUSION: In the sacroiliitis of AS, two findings predominate: 1) synovitis and subchondral bone marrow changes offer a more rational explanation for widespread joint destruction than does enthesitis; and 2) an unusual form of chondroid metaplasia contributes to ankylosis.     

软骨下骨与骨性关节炎病变的发生发展：从基础研究到临床治疗

骨性关节炎（OA）是软骨与骨的退行性变过程。软骨下骨是构成关节结构和功能的基本单位之一,维持软骨正常结构和功能。在复杂应力和生物学作用下,OA软骨下骨的重塑和结构改变使软骨承受更高的应力。软骨下骨内血管生成和结构病变扩大了骨软骨异常交流途径,软骨下骨产生的代谢调节因子通过异常生物学交流直接促进软骨退变。研究软骨下骨内细胞及其变化,血管生成与骨软骨间生物学交流,揭示软骨下骨重塑和结构变化特点,探寻改善骨重塑治疗方法,将有利于延缓OA病变进展,有效防治OA。     

Immunpathologie bei der ankylosierenden Spondylitis und anderen Spondyloarthritiden

Histomorphological analysis shows at least two different patterns in patients with ankylosing spondylitis. Bone marrow edema, lymphocytic infiltrates, increased osteoclast density and increased microvessel density are typical findings in acute inflammation. In areas of new bone formation newly formed trabecular bone shows formation of fibrous tissue in the bone marrow with new cartilage formation and persistently high microvessel density. Morphological changes reminiscent of endochondral ossification can also be observed. Compared to peripheral joints, such as the knee, synovitis is not a predominant finding in the spine, the sacroiliac joints and the hip. Enthesitis is characterised by lymphocytic infiltrates around fibrous cartilage followed by subsequent ankylosis. The molecular mechanisms which promote the transition from inflammation to new bone formation in patients with ankylosing spondylitis are not well understood.     

Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow

OBJECTIVE: Previous histopathologic and magnetic resonance imaging studies suggest that the subchondral bone marrow might be the primary site of inflammation in patients with ankylosing spondylitis (AS) and that this might be reflected by inflammation found in hip joints. The aim of this study was to conduct an immunohistologic assessment of the bone-cartilage interface and subchondral bone marrow in AS patients with hip arthritis. METHODS: We collected femoral heads from patients with AS, osteoarthritis (OA), and rheumatoid arthritis (RA) who were undergoing hip replacement. The subchondral bone marrow and bone-cartilage interface were assessed immunohistochemically by evaluating infiltrating T cells, microvessel density, and osteoclasts. Areas of the femoral head surface with and without cartilage were assessed separately. RESULTS: At sites with surface cartilage, we found subchondral infiltration of CD3+ T cell aggregates at significantly higher numbers in AS patients as compared with OA patients, but not RA patients. At sites of complete cartilage destruction, the frequency of CD3+ T cell aggregates was significantly reduced as compared with sites with cartilage on the surface in AS patients, but not in RA patients. Similar differences were found for CD4+ and CD8+ T cells. Only at sites with surface cartilage, but not those without, angiogenesis and osteoclastic foci in the subchondral bone marrow in AS patients were significantly increased as compared with RA patients and with OA patients. CONCLUSION: These findings suggest that the subchondral bone marrow and bone-cartilage interface are primary sites of inflammation in AS and that cartilage might be necessary for the induction of inflammation.     

Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: Evaluation of the bone–cartilage interface and subchondral bone marrow

Objective

Previous histopathologic and magnetic resonance imaging studies suggest that the subchondral bone marrow might be the primary site of inflammation in patients with ankylosing spondylitis (AS) and that this might be reflected by inflammation found in hip joints. The aim of this study was to conduct an immunohistologic assessment of the bone–cartilage interface and subchondral bone marrow in AS patients with hip arthritis.

Methods

We collected femoral heads from patients with AS, osteoarthritis (OA), and rheumatoid arthritis (RA) who were undergoing hip replacement. The subchondral bone marrow and bone–cartilage interface were assessed immunohistochemically by evaluating infiltrating T cells, microvessel density, and osteoclasts. Areas of the femoral head surface with and without cartilage were assessed separately.

Results

At sites with surface cartilage, we found subchondral infiltration of CD3+ T cell aggregates at significantly higher numbers in AS patients as compared with OA patients, but not RA patients. At sites of complete cartilage destruction, the frequency of CD3+ T cell aggregates was significantly reduced as compared with sites with cartilage on the surface in AS patients, but not in RA patients. Similar differences were found for CD4+ and CD8+ T cells. Only at sites with surface cartilage, but not those without, angiogenesis and osteoclastic foci in the subchondral bone marrow in AS patients were significantly increased as compared with RA patients and with OA patients.

Conclusion

These findings suggest that the subchondral bone marrow and bone–cartilage interface are primary sites of inflammation in AS and that cartilage might be necessary for the induction of inflammation.

     

Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis.

OBJECTIVE: To test the hypothesis that bisphosphonate treatment has a chondroprotective effect in the carrageenan model of inflammatory arthritis (IA). METHODS: Experimental IA was induced in rabbits by intraarticular injections of carrageenan. One group also received subcutaneous injections of zoledronate, a new bisphosphonate. After 4 weeks, the joints were harvested. Articular cartilage degradation and the degree of synovitis were assessed by light microscope using qualitative grading scores. Articular cartilage and subchondral and cancellous bone were evaluated histomorphometrically. Bone microhardness was measured. RESULTS: Carrageenan injected knees showed changes of inflammatory arthritis with cartilage erosion. Zoledronate treatment partially protected the articular cartilage from degradation. This effect was unlikely due to an antiinflammatory effect of the drug as the carrageenan induced synovitis was unaffected by zoledronate treatment. The treatment preserved subchondral bone thickness and cancellous bone volume and prevented focal breaks in the osteochondral barrier. The subchondral bone hardness was also maintained. CONCLUSION: Zoledronate had a partial effect in a rabbit model of inflammatory arthritis. The chondroprotection may be due to the prevention of bone resorption. By maintaining an intact subchondral bone, normal joint loading may have been maintained and contact between the bone marrow and the articular cartilage averted.     

Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders

OBJECTIVE: To describe the basis for entheseal-associated bone disease in the spondylarthritides, by analyzing microanatomic and histopathologic relationships between soft tissue, bone cortex, and adjacent trabeculae. METHODS: Serial sections from 52 entheses were examined; these entheses encompassed small and large insertions in the upper limb (n = 21), lower limb (n = 27), and spine (n = 4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and reparative changes were evaluated. Contact radiographs were used to ascertain the relationship between entheses and the trabecular network. RESULTS: At virtually all fibrocartilaginous entheses, the deep cortical boundary was extremely thin (typically 50-600 microm) or indistinguishable, and 96% of entheses had small holes in the cortical shell (typically 100-400 microm wide). Such regions were frequent sites of bone formation and renewal (96%) and microdamage (31%); these changes were more common in the lower limb. The presence of blood vessels near holes in the cortical shell was common; in 85% of attachments, blood vessels were present on the soft tissue side of the enthesis. Highly orientated trabeculae were more obvious in the lower limb than the upper limb (59% versus 29%). CONCLUSION: The trabecular network supporting the cortical shell is an integral part of the enthesis, transferring load to an extensive skeletal region. In many cases, tendons/ligaments are anchored directly to such networks. This functional integration is associated with microdamage and repair at the hard tissue-soft tissue interface. These findings have implications for understanding bone involvement in SpA and for the SpA concept in general, especially the hypothesis that enthesis-bone architecture may be important in disease initiation.     

Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling

PURPOSE OF REVIEW: This review deals with new findings highlighting the concept of cross-talk between subchondral bone tissue and articular cartilage that may be crucial for the initiation and/or progression of osteoarthritis. In this review, new factors either produced by subchondral bone tissue or modifying osteoblast metabolism, yet implicated in osteoarthritis, are discussed. RECENT FINDINGS: The development of cartilage degeneration is concomitant with subchondral bone thickness in osteoarthritis, whereas it is related to higher subchondral bone activity and dysregulation in the synthesis of bone proteins. As an immediate consequence, homotrimers of type 1 collagen are formed that could lead to undermineralization of this tissue. This dysregulation also leads to abnormal production of different factors by osteoblasts such as prostaglandins, leukotrienes, and growth factors. Because microcracks or neovascularization provide a link between the subchondral bone tissue and articular cartilage, these factors could contribute to the abnormal remodeling of osteoarthritic cartilage. SUMMARY: These findings have an immediate implication for research because new tools need to be developed to study the subchondral bone-cartilage functional unit. Moreover, it could lead to a possible cure for osteoarthritis because this pathology should be considered both a bone and cartilage disease.     

Vascular pathology and osteoarthritis

There is mounting evidence that vascular pathology plays a role in the initiation and/or progression of the major disease of joints: osteoarthritis (OA). Potential mechanisms are: episodically reduced blood flow through the small vessels in the subchondral bone at the ends of long bones, and related to this, reduced interstitial fluid flow in subchondral bone. Blood flow may be reduced by venous occlusion and stasis or by the development of microemboli in the subchondral vessels. There are several likely effects of subchondral ischaemia: the first of these is compromised nutrient and gas exchange into the articular cartilage, a potential initiator of degradative changes in the cartilage. The second is apoptosis of osteocytes in regions of the subchondral bone, which would initiate osteoclastic resorption of that bone and at least temporarily reduce the bony support for the overlying cartilage. It may be important to recognize these potential aetiological factors in order to develop more effective treatments to inhibit the progression of OA.     

Subchondral bone and cartilage damage: A prospective study in older adults

Objective

There is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss.

Methods

A total of 341 subjects (mean age 63 years, range 52–79 years) underwent measurement at baseline and ∼2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0–4), and bone area were determined using T1‐weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x‐ray absorptiometry.

Results

In multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (β = −34.9 per 1 SD increase, 95% CI −49.8, −20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss.

Conclusion

The results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage.

     

骶髂关节病变病理学与影像学诊断的相关性

目的通过了解骶髂关节炎病理特点,并以病理结果为标准,探讨病理表现与放射性核素单光子发射计算机断层成像术(single-photon emission computed tomography,SPECT)、磁共振显像(magnetic resonance imaging,MRI)、计算机断层扫描(computed tomography,CT)、X线等影像学检查的关系。方法对中轴型脊柱关节炎患者进行CT引导下骶髂关节(sacroiliac joint,SIJ)穿刺,所得组织进行病理检查,并同时行SIJ的SPECT、MRI、CT和X线检查,按组织病理结果分为SIJ炎组和无炎性反应组。结果 36例患者获得组织有软骨、软骨下骨板、关节滑膜、骨髓、肌腱或韧带附着点等。获得率以软骨为最高,继以软骨下骨板、关节滑膜、骨髓和韧带附着点,各占92%、83%、75%、72%、22%;其中28例(2836,78%)患者SIJ炎病理变化包括软骨(93%)和软骨下骨板改变(75%)、滑膜炎(64%)、骨髓炎(46%)、附着点炎(32%),8例(22%)未发现有SIJ炎改变。MRI示29例(81%)患者共56个SIJ可见不同程度的异常信号改变,软骨线改变、软骨下骨板改变、骨髓水肿、脂肪沉积、骨质硬化分别为82%、71%、65%、59%、76%;SPECT示29例(81%)共52个SIJ可见骶髂关节感兴趣区的放射性比值有不同程度的升高,23例(64%)CT阳性,19例(53%)X线阳性。以病理结果为标准,SPECT、MRI、CT、X线的阳性预测值分别为89.6%、93.1%、95.6%、94.7%,敏感性分别为92.8%、96.4%、73.3%、64.2%,特异性分别62.5%、75.0%、87.5%、87.5%。4种诊断方法的受试者工作特征曲线下面积分别为0.79、0.84、0.83、0.76。结论病理检查是诊断Sl J炎和活动性炎性反应的主要方法。MRI和SPECT的相互补充,能提高骶髂关节活动性炎症的敏感性和特异性。MRI和SPECT的诊断价值与CT和X线相当,并可通过对炎症的活动度进行量化,有利于随访和疗效的评价,是诊断SIJ炎重要的辅助手段。     

Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis?

The existing data are consistent with the view that reactivation of the secondary center of ossification and not the stiffening of the metaphyseal trabecular bone is a mechanism of cartilage loss in idiopathic OA. The stiffening of the subchondral calcified structures would appear to be etiologically incidental and, as the arthrotic process progresses, sometimes locally transient. It is also now clear that although the apparent density of the subchondral cortical plate increases because of thickening of the plate as the OA process progresses, the elastic modulus of the bone might be reduced locally because of increases in vascularization and in the rate of bony remodeling subjacent to the cartilage. Microcracks in the subchondral mineralized tissues might contribute to degeneration of the hyaline cartilage by initiating vascular invasion of the calcified cartilage, leading to reactivation of the tidemark and enchondral ossification with subsequent thinning of the overlying articular cartilage. The thinning would tend to increase shear stresses at the base of the articular cartilage [38], overwhelming the ability of the cartilage to repair itself, resulting in cartilage degeneration. The pathogenesis of cartilage breakdown in OA is a biological and a mechanical process. OA can be understood only if the relationship between the mechanics and the biology is fully appreciated. Failure to properly absorb impact leads to microdamage in the subchondral plate and calcified cartilage. The authors believe that this action causes the secondary center of ossification at the tidemark to advance by enchondral ossification, leading to thickening of the mineralized tissues and thinning of the overlying hyaline articular cartilage. Microcracks will cause the initiation of targeted remodeling, accounting for the increased turnover and reduced material density of the subchondral plate. The resultant thinning of the articular cartilage might lead to initiation of further microdamage in bone and cartilage through a positive feedback mechanism, which can ultimately lead to complete loss of the articular cartilage. In this view, the mechanical overload that initiates microdamage of the subchondral bone provokes a biological response that potentiates the progression of articular cartilage damage in OA.     

Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis

OBJECTIVE: To examine the effect of the bisphosphonate NE- 10035 on bone histomorphometry and bone dynamics in dogs after transection of the anterior cruciate ligament (ACL), and to determine, in a placebo controlled trial, whether treatment modified the severity of pathologic changes of osteoarthritis (OA) in the unstable joint. METHODS: Ten adult male mongrel dogs underwent ipsilateral ACL transection. Five dogs then received daily subcutaneous injections of NE-10035 on 5 days per week for 12 weeks beginning the day after surgery. The other 5 dogs served as concurrent OA controls and received subcutaneous injections of saline on the same schedule. At sacrifice, 12 weeks after ACL transection, the articular cartilage and synovium of both knees of each dog were evaluated grossly and histologically and the water content and uronic acid concentration of the articular cartilage was determined. Fifteen days before sacrifice, each dog was injected with the fluorochrome label calcein. The injection regimen was repeated 10 days after the initial date. At sacrifice, static and dynamic variables of bone formation were assessed and bone resorption was quantified. RESULTS: In the OA knee of the control group, bone formation and resorption were markedly increased. NE-10035 markedly reduced both formation and resorption of cancellous subchondral bone, but had no effect on osteophyte formation or pathologic changes of OA in the articular cartilage, which were mild in both treatment groups. Water content of the OA cartilage was increased by about 8% in both treatment groups. However, among the controls, the mean uronic acid concentration of the OA cartilage was increased by about 30% in comparison with values for the contralateral knee, while in the NE-10035 treatment group the mean uronic acid concentration of OA knee cartilage was about 15% lower in the active treatment group than in cartilage from the contralateral knee (p = 0.003 for the difference in OA knee uronic acid concentration between the 2 treatment groups, relative to that in the contralateral knee). CONCLUSION: The antiresorptive agent employed in this study effectively reduced turnover of subchondral bone in the OA joint, consistent with the coupling of bone formation to bone resorption at that site. Nonetheless, over the 12 week period of the study it had no effect on osteophyte formation, in which bone formation occurs via enchondral ossification and is not linked to bone resorption, and, despite the clear inhibition of bone turnover in the OA knee of the active treatment group, did not affect the severity of cartilage changes of OA. It should be noted, however, that although treatment with this antiresorptive agent did not affect the level of chondropathy, the cartilage changes in both treatment groups were relatively mild and the sample size relatively small. Additional studies with a larger number of animals and a longer period of observation (to increase the severity of pathology) are warranted to determine whether the inhibition of bone turnover and the decrease in proteoglycan concentration that resulted from therapy will affect articular cartilage degeneration in the OA joint.     

软骨下骨成骨细胞在骨性关节炎中的作用与机制

骨性关节炎是一种骨组织代谢疾病,软骨下骨成骨细胞直接参与骨性关节炎的病理过程。成骨细胞表达异常的生物学表型与软骨下骨结构和功能改变密切相关,其可使软骨承受更高的应力;软骨下骨成骨细胞产生的代谢调节因子通过骨和软骨间微结构直接促进软骨细胞退变。免疫和脂类代谢通过成骨细胞调节骨组织代谢,参与骨性关节炎病变过程。进一步阐明软骨下骨成骨细胞在骨性关节炎病变过程中的作用和机制,可为骨性关节炎研究和治疗提供新方法和思路。     

The biomarker assey for cartilage destruction in rheumatoid arthritis. -Which molecules can reflect cartilage breakdown in RA?-

Rheumatoid arthritis (RA) is characterized as inflammatory disease associated with cartilage degradation and subchondral bone erosion. RA is an autoimmune disease that has genetic and environmental backgrounds. The preservation of a functional articular cartilage enables the survival of a tissue that covers articulating surfaces in affected joints. The extracellular matrix of articular cartilage provides this tissue with its gprimary strength, resistance to deformation, and ability to dissipate load in the joint. Many research had been designed for trying to measure the remodeling and pathologic events in RA caritlage. The many matrix molecules, and their degradation products, are released from cartilage and bone and can be detected biochemically and immunologically in the serum and Joint fluids. Before evaluating the data of biomarkers revealed in pathologic conditions such as RA and OA, our skeletal system is built and maintained by a balance between synthesis and degradation. Furthermore this balance varies considerably from one person to another. It is nortworhy that the off-balance between synthesis and degradation lead to cartilage destruction. The use of many of the biomarker assays for matrix turnover offers the evidences to evaluate whether the treatments designed to inhibit the joint damage may successfully work in specific RA patients.     

The effects of glucosamine hydrochloride on subchondral bone changes in an animal model of osteoarthritis

OBJECTIVE: To quantify periarticular subchondral bone changes in a rabbit model of experimental osteoarthritis (OA), and to determine the effects of continuous administration of a clinically relevant dose of glucosamine HCl on subchondral bone changes in this model. METHODS: Anterior cruciate ligament transection (ACLT) was performed on the left femorotibial joints of 16 rabbits to induce OA. Ten rabbits that did not undergo ACLT served as unoperated controls. Eight rabbits that underwent ACLT and 6 control rabbits were treated with 100 mg of glucosamine daily, and the others were given a placebo. The articular cartilage was evaluated macroscopically and graded at the time of necropsy, 8 weeks after ACLT. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry on the dissected distal femur and proximal tibia. Subchondral trabecular bone turnover, architecture, and connectivity, as well as subchondral plate thickness and mineralization were studied on the undecalcified tibia sections from each animal. RESULTS: Eight weeks after ACLT, most of the operated joints had various degrees of cartilage damage and fibrillation. Compared with the control group, the ACLT group had significantly increased subchondral bone turnover and lower BMD, bone volume, connectivity, and bone mineralization. The high bone turnover was significantly reduced in glucosamine-treated animals that underwent ACLT. In fact, there were no significant differences between the ACLT/glucosamine group and the control/glucosamine group in most of the bone parameters studied. CONCLUSION: This study shows that subchondral bone turnover, structure, and mineralization are significantly altered in the early stages of experimental OA, and that these changes are attenuated by glucosamine treatment.     

Tartrate-resistant acid phosphatase-positive cells in the synovial–cartilage junction and bone marrow during the progression of collagen-induced arthritis in adult rats

We investigated the time-course changes in bone destruction in rats with collagen-induced arthritis (CIA). The synovial–cartilage junction (SCJ) and epiphyseal bone marrow of the femoral posteromedial condyle in CIA rats were evaluated histologically and immunohistologically at 2, 3, 4, 6, and 8 weeks after sensitization. Two weeks after sensitization, tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells formed resorption lacunae on the lateral side of the cortical bone under the SCJ. No resorption lacunae were observed in bone marrow. Three weeks after sensitization, resorption lacunae on the lateral side of the cortical bone expanded, but no bone marrow invasion by pannus was observed. In bone marrow, many TRAP-positive multinuclear cells appeared and formed resorption lacunae in subchondral bone. Four weeks after sensitization, cortical bone was destroyed, and pannus had invaded the bone marrow. After six weeks, trabecular bone and subchondral bone plate were extensively resorbed by TRAP-positive cells. Bone destruction in CIA began with the appearance of TRAP-positive cells on the lateral side of the cortical bone under the SCJ, followed by the TRAP-positive multinuclear cells in bone marrow, which were morphologically unconnected to the SCJ lesions. These histological findings suggested that bone destruction in the early stage of arthritis occurred in two anatomically different regions.     

The effects of bone turnover rate on subchondral trabecular bone structure and cartilage damage in the osteoarthritis rat model

The effects of bone turnover rate on subchondral trabecular changes and cartilage destruction were evaluated in an iodoacetate-induced osteoarthritis rat model. Thirty female rats were randomly divided into three groups as the ovariectomized group, the no-treatment group and the bisphosphonate medication group. Arthritis was induced by a single intra-articular iodoacetate injection into the right tibiofemoral joint. Eight weeks after this injection, tibiofemoral joints on both sides were scanned with a micro-CT. Subchondral trabecular indices were measured on both sides of the tibial lateral condyle epiphysis. In the ovariectomized group, the percentage of bone volume, trabecular thickness and trabecular bone pattern factor of the arthritic sides were lower than those of the control sides, while trabecular separation and structure model index of the arthritic sides were higher than those of the control sides (p < 0.05). In the no-treatment group, only trabecular thickness of the arthritic sides was lower than in the control sides (p < 0.05). In the bisphosphonate medication group, trabecular indices were no different between the arthritic and control sides. Articular cartilage destruction and severity of arthritis increased significantly in the order: ovariectomized group < no-treatment group < bisphosphonate medication group (p < 0.05). After osteoarthritis development, severities of subchondral trabecular changes appeared to be strongly affected by bone turnover rate. Furthermore, a correlation was found between cartilage destruction severity and subchondral trabecular change in the intra-articular iodoacetate-injected osteoarthritis rat model.     

Anatomic structures involved in early- and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging

OBJECTIVE: To localize inflammatory and chronic changes to defined areas in the sacroiliac joints in patients with early-stage compared with late-stage spondylarthritis (SpA), using magnetic resonance imaging (MRI). METHODS: Using MRI, 93 patients with SpA and inflammatory back pain who had radiographs of the sacroiliac joints were examined, comprising 31 patients with ankylosing spondylitis (AS) and 62 with other SpA subsets, including 48 with undifferentiated SpA (uSpA). MRI was performed using T1-weighted, T2*-weighted, STIR, and dynamic contrast-enhanced (gadolinium diethylenetriaminepentaacetic acid) sequences. Two readers retrospectively analyzed the images by differentiating 9 areas of the sacroiliac joints: the ventral and caudal joint capsule, cavum, subchondral bone, bone marrow, ligament entheses, and ligaments; the sacral and iliac sides were tabulated separately. RESULTS: By MRI, sacroiliitis was more often bilateral in AS (84%) than in uSpA (48%) (P = 0.01). Inflammatory changes were found in a mean +/- SD 4.7 +/- 2.9 regions/joint, with involvement of 4.5 +/- 3.2 regions in early disease versus 5.2 +/- 2.3 regions in late disease (P not significant [NS]). Involvement of the iliac side of the sacroiliac joints was found to be more frequent than the sacral side in early disease (58% versus 48%; P < 0.01) as compared with that in late disease (58% versus 63%; P NS). The dorsocaudal parts of the synovial joint and the bone marrow were the most frequently inflamed structures in early disease (P < 0.001 for ventral versus dorsal joint capsule). In contrast, involvement of the entheses was more common in advanced disease (early 43% versus late 86%; P < 0.001). Similarly, the ligaments were more frequently involved in the late stages (early 26% versus late 40%; P = 0.06). Both patterns of bone marrow inflammation (focal and diffuse) were observed in equal frequencies in early and late disease (17% and 42% versus 26% and 43%, respectively; P NS). HLA-B27-positive patients (n = 80) had more entheseal involvement than did HLA-B27-negative patients (n = 13) (60% versus 39%; P = 0.05). HLA-B27-negative patients had a shorter disease duration (2.2 years versus 4.4 years; P = 0.05) and were more often female (62%; P = 0.02). When all pathologic changes were assessed, the STIR sequence (performed in 62 patients) was less sensitive than the contrast-enhanced sequences in that it was not able to show all relevant changes in 27% of these patients (n = 17), failing to reveal inflammation of the cavum in 15 patients and of the bone marrow and joint capsule in 1 patient each. CONCLUSION: As visualized by MRI, sacroiliitis in SpA is characterized by involvement of different joint structures. Whereas the iliac and the sacral side of the sacroiliac joints are almost equally affected, the dorsocaudal synovial part of the joint is involved significantly more often than the ventral part, especially in early disease. Sacroiliac enthesitis is not a special feature of early sacroiliac inflammation.     

Vascular mechanisms in osteoarthritis

Superficial injury and fibrillation of articular cartilage as a consequence of ageing, genetic, hormonal or mechanical factors are not necessarily associated with joint pain. However, failure of joint cartilage accompanied by synovitis and abnormalities in subchondral bone and its vasculature generally is, the syndrome being known as osteoarthritis. We suggest that the progression of early cartilage fibrillation to symptomatic OA arises initially as a consequence of the release into synovial fluid of cartilage-derived antigens that activate joint lining macrophages and circulating leukocytes, thereby establishing a synovitis. Pro-inflammatory mediators and pro-coagulant factors etc. not only perpetuate cartilage destruction but also promote a state of hypercoagulation, hypofibrinolysis, thrombosis and ischaemic bone necrosis at compromised sites such as in the subchondral vasculature. These events are augmented by ageing and associated hormonal changes. On the basis of this hypothesis we suggest that anti-thrombotic/anti-lipidaemic agents that also exhibit anti-inflammatory activity could be effective anti-osteoarthritic drugs. Experimental studies are described which support this proposal.