Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation

Background  

Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would have similar dual actions on both bone and cartilage turnover, as reported previously with some SERMS and HRT.     

Post-traumatic glenohumeral cartilage lesions: a systematic review

Background  

Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present.     

Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling

Purpose

The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access.

Methods

A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed.

Results

As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing.

Conclusion

The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.     

Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone

The elastic moduli of calcified cartilage and subchondral bone tissues were measured experimentally with use of a three-point bending test. Specimens were obtained from a bovine patella and the distal end of a bovine femur, from two different animals. Fifteen specimens were tested as “pure” subchondral bone beams, and 15 were tested as composite calcified cartilage/subchondral bone beams. A least-squares optimization scheme was used to obtain modulus values from the composite beams. The elastic modulus for subchondral bone calculated from the “pure” subchondral bone beams was 2.3 ± 1.5 GPa (3.9 ± 1.5 GPa for specimens from the femur and 1.6 ± 0.7 GPa for specimens from the patella). The composite beam optimization resulted in a modulus for subchondral bone of 5.7 ± 1.9 GPa and a modulus for calcified cartilage of 0.32 ± 0.25 GPa. The modulus for the calcified cartilage was more than an order of magnitude lower than the modulus of the underlying subchondral bone. This supports the idea that the zone of calcified cartilage forms a transitional zone of intermediate stiffness between the articular cartilage and the subchondral bone.     

Extracorporeal shockwave therapy shows chondroprotective effects in osteoarthritic rat knee

Purpose  

This study investigated the effects of extracorporeal shockwave therapy (ESWT) on the subchondral bone and articular cartilage in the initiation of osteoarthritis of the knee in rats.     

正常膝关节软骨钙化层形态结构研究

目的探索关节软骨钙化层的结构形态及其与软骨非钙化层和软骨下骨之间的界面连接方式。方法组织库获取自愿捐献的人体正常股骨髁新鲜标本20个,男10个,女10个;年龄17～45岁。常规制备石蜡横、纵切片,番红O／固绿和冯库萨染色观察钙化层形态结构;扫描电镜观察软骨各层之间的界面连接方式;连续切片结合建模技术建立骨软骨三维模型。结果关节骨软骨复合组织番红O／固绿染色结果示软骨红染,软骨下骨蓝染,钙化层位于潮线与黏合线之间;冯库萨染色结果示钙化层黑染,结构及边界清晰,上界面以波浪状潮线结构与非钙化层紧密连接,下界面以凹凸不平的梳齿状结构与软骨下骨相互锚合：关节骨软骨剥离面及断面扫描电镜示钙化层与非钙化层以沟壑镶嵌方式相互嵌合;关节骨软骨复合组织纵切面观察,钙化层与软骨下骨间的黏合线呈凹凸不平的梳齿状结构;骨软骨三维模型观察结果与关节软骨自然剥离横断面扫描电镜观察结果基本一致。结论钙化层是关节软骨的重要结构,它通过特有界面连接方式将软骨牢牢固定在软骨下骨上。     

Subchondral bone sclerosis and cancellous bone loss following OA induction depend on the underlying bone phenotype

Objectives

Osteoarthritis (OA) is increasingly considered a disease of the whole joint, yet the interplay between the articular cartilage and the subchondral bone remains obscure. We here set out to investigate the impact of bone mass on the progression of surgically induced knee OA in the mouse.

Association between subchondral bone structure and osteoarthritis histopathological grade

Despite increasing evidence that subchondral bone contributes to osteoarthritis (OA) pathogenesis, little is known about local changes in bone structure compared to cartilage degeneration. This study linked structural adaptation of subchondral bone with histological OA grade. Twenty‐five osteochondral samples of macroscopically different degeneration were prepared from tibiae of 14 patients. Samples were scanned with micro‐computed tomography (μCT) and both conventional structural parameters and novel 3D parameters based on local patterns were analyzed from the subchondral plate and trabecular bone. Subsequently, samples were processed for histology and evaluated for OARSI grade. Each bone parameter and OARSI grade was compared to assess structural adaptation of bone with OA severity. In addition, thicknesses of cartilage, calcified cartilage, and subchondral plate were analyzed from histological sections and compared with subchondral bone plate thickness from μCT. With increasing OARSI grade, the subchondral plate became thicker along with decreased specific bone surface, while there was no change in tissue mineral density. Histological analysis showed that subchondral plate thickness from μCT also includes calcified cartilage. Entropy of local patterns increased with OA severity, reflecting higher tissue heterogeneity. In the trabecular compartment, bone volume fraction and both trabecular thickness and number increased with OARSI grade while trabecular separation and structure model index decreased. Also, elevation of local patterns became longitudinal in the subchondral plate and axial transverse in trabecular bone with increasing OARSI grade. This study demonstrates the possibility of radiological assessment of OA severity by structural analysis of bone. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:785–792, 2017.

     

Three-dimensional visualization and pathologic characteristics of cartilage and subchondral bone changes in the lumbar facet joint of an ovariectomized mouse model

Background Context

Low back pain (LBP) is more prevalent among postmenopausal women than men. Ovariectomy (OVX) is an established animal model that mimics the estrogen deficiency of postmenopausal women. Little is known about the three-dimensional (3D) morphologic properties of cartilage and subchondral bone changes in the lumbar facet joint (LFJ) of an OVX mouse model.

In situ measurement of transport between subchondral bone and articular cartilage

Subchondral bone and articular cartilage play complementary roles in load bearing of the joints. Although the biomechanical coupling between subchondral bone and articular cartilage is well established, it remains unclear whether direct biochemical communication exists between them. Previously, the calcified cartilage between these two compartments was generally believed to be impermeable to transport of solutes and gases. However, recent studies found that small molecules could penetrate into the calcified cartilage from the subchondral bone. To quantify the real‐time solute transport across the calcified cartilage, we developed a novel imaging method based on fluorescence loss induced by photobleaching (FLIP). Diffusivity of sodium fluorescein (376 Da) was quantified to be 0.07 ± 0.03 and 0.26 ± 0.22 µm²/s between subchondral bone and calcified cartilage and within the calcified cartilage in the murine distal femur, respectively. Electron microscopy revealed that calcified cartilage matrix contained nonmineralized regions (～22% volume fraction) that are either large patches (53 ± 18 nm) among the mineral deposits or numerous small regions (4.5 ± 0.8 nm) within the mineral deposits, which may serve as transport pathways. These results suggest that there exists a possible direct signaling between subchondral bone and articular cartilage, and they form a functional unit with both mechanical and biochemical interactions, which may play a role in the maintenance and degeneration of the joint. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1347–1352, 2009     

Distribution of fluoride in calcified cartilage of a fluoride-treated osteoporotic patient

Subchondral bone and calcified cartilage from a femoral head of a 74-year-old osteoporotic woman treated for 30 months with sodium fluoride were analyzed. The fluoride content of the calcified tissues was determined by a specific ion electrode, and the topographic distribution pattern of fluoride was determined with an electron microprobe. The fluoride content in calcified cartilage (0.39% of ash) was higher than in neighboring subchondral bone (0.28% of ash). Line scan and X-ray images indicated a high concentration of fluoride in the outer layer of calcified cartilage lining the uncalcified cartilage, as well as in the inner layer of the subcortical endosteal bone. This study shows that calcified cartilage is an important site of fluoride deposition, and suggests that the accumulation of fluoride is related to the calcification process.     

Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis

Purpose

Impairment of subchondral bone density and quality aggravates cartilage damage in osteoarthritis (OA). Accordingly, we assessed whether improving microstructure and quality at subchondral bone by the bone-forming agent parathyroid hormone (PTH) [1-34] prevent cartilage damage progression in a rabbit model of OA preceded by osteoporosis (OP).

Methods

OP was induced in 20 female rabbits. At week 7, these rabbits underwent knee surgery to induce OA and, at week 12, they started either saline vehicle (n = 10) or PTH (n = 10) for 10 weeks. Ten healthy animals were used as controls. At week 22, microstructure was assessed by micro-computed tomography and bone remodelling by protein expression of alkaline phosphatase (ALP), metalloproteinase-9 (MMP9), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) at subchondral bone. Cartilage damage was evaluated using Mankin score.

Results

PTH reversed the decrease of bone area/tissue area, trabecular thickness, plate thickness, polar moment of inertia, ALP expression and OPG/RANKL ratio, as well as counteracted the increase of fractal dimension and MMP9 expression at subchondral bone of osteoarthritis preceded by osteoporosis (OPOA) rabbits compared to vehicle administration (P < 0.05). Likewise, PTH decreased cartilage damage severity in OPOA rabbits. Good correlations were observed between subchondral bone structure or remodelling parameters, and cartilage Mankin score.

Conclusions

Improvement of microstructural and remodelling parameters at subchondral bone by PTH [1-34] contributed to prevent cartilage damage progression in rabbits with early OPOA. These findings support the role of subchondral bone in OA. Further studies are warranted to establish the place of bone-forming agents as potential treatment in OA.     

Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects

OBJECTIVE: We have previously shown that microfractured ovine defects are repaired with more hyaline cartilage when the defect is treated with in situ-solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with autologous whole blood. The objectives of this study were (1) to characterize chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation model in order to determine the effects of the chitosan-GP/blood implant and of debridement on the formation of incipient cartilage repair tissue. METHODS: Blood clots were characterized by histology and in vitro clot retraction tests. Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were pierced with four microdrill holes and filled with a chitosan-GP/blood implant or allowed to bleed freely as a control. At 1 day post-surgery, initial defects were characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral repair tissues between or through the drill holes were evaluated by histology, histomorphometry, collagen type II expression, and stereology (n=16). RESULTS: Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the formation of a more integrated and hyaline repair tissue above a more porous and vascularized subchondral bone plate compared to drilling alone. Correlation analysis of repair tissue between the drill holes revealed that the absence of calcified cartilage and the presence of a porous subchondral bone plate were predictors of greater repair tissue integration with subchondral bone (P<0.005), and of a higher total O'Driscoll score (P<0.005 and P<0.01, respectively). CONCLUSIONS: Chitosan-GP/blood implants applied in conjunction with drilling, compared to drilling alone, elicited a more hyaline and integrated repair tissue associated with a porous subchondral bone replete with blood vessels. Concomitant regeneration of a vascularized bone plate during cartilage repair could provide progenitors, anabolic factors and nutrients that aid in the formation of hyaline cartilage.     

The structure of the human subchondral plate

To study the anatomy of subarticular bone and cartilage, fresh specimens of cartilage on bone from the human shoulder, hip and knee were treated with bleach or papain, or were fixed and decalcified. All were compared using scanning electron microscopy. Papain digestion selectively removed cartilage to the tidemark. The tidemark contour was highly variable; irregularities were indirectly related to degenerative lesions and were most prominent in peripheral non-weight-bearing areas of joints with central fibrillation. Decalcification exposed the interface between the bone and calcified cartilage. Collagen fibrils in articular cartilage did not interdigitate with those of bone. The subchondral bone was appositional, avascular, smooth and very thin in most areas of human joints. Perforations through subchondral bone or calcified cartilage were rare. Bleach maceration destroyed important details.     

Age-related histological changes in rat mandibular condyle

The effect of aging on rat mandibular condyle was histologically assessed using 1-, 4-, 9-, and 16-month-old male Fischer rats (Eight rats of each group). The medial and anterior portions of the condyle protruded with age. The hypertrophic cell layer of the condylar cartilage occurring up to 4 months was no longer observable at 9 months, after which calcification of the cartilage layer with a tidemark was featured. The chondrocytes in the calcified cartilage layer were reduced in size and intensely stained by toluidine blue. A mineralizing front was formed parallel to, and migrated toward, the condyle surface. At 9 months, osteon-like osteogenesis occurred around blood vessels on the border between the calcified cartilage and the subchondral bone. Condyles of 16-month-old rats exhibited osteosclerotic changes. The calcified cartilage of the middle portion of the condyle formed a remarkably thick layer. The increased volume of the trabecular bone appears to lead to enhanced osteosclerotic changes of the condyle. The aging-related protrusion of the anterior and medial portions of the condyle could be the result of a combination of mechanical forces, e.g., occlusion and mastication. Further, our study revealed that the turnover from cartilage to bone occurring in rat condyle through the process of aging involved an osteon-like bone formation around the blood vessels on the border between the calcified cartilage layer and the bone. This process differs from the endochondral ossification process observed in younger rats.     

Osteochondritis Dissecans Knee Histology Studies Have Variable Findings and Theories of Etiology

Background

Although many etiological theories have been proposed for osteochondritis dissecans (OCD), its etiology remains unclear. Histological analysis of the articular cartilage and subchondral bone tissues of OCD lesions can provide useful information about the cellular changes and progression of OCD. Previous research is predominantly comprised of retrospective clinical studies from which limited conclusions can be drawn.

Questions/purposes

The purposes of this study were threefold: (1) Is osteonecrosis a consistent finding in OCD biopsy specimens? (2) Is normal articular cartilage a consistent finding in OCD biopsy specimens? (3) Do histological studies propose an etiology for OCD based on the tissue findings?

Methods

We searched the PubMed, Embase, and CINAHL databases for studies that conducted histological analyses of OCD lesions of the knee and identified 1560 articles. Of these, 11 met our inclusion criteria: a study of OCD lesions about the knee, published in the English language, and performed a histological analysis of subchondral bone and articular cartilage. These 11 studies were assessed for an etiology proposed in the study based on the study findings.

Results

Seven of 11 studies reported subchondral bone necrosis. Four studies reported normal articular cartilage, two studies reported degenerated or irregular articular cartilage, and five studies found a combination of normal and degenerated or irregular articular cartilage. Five studies proposed trauma or repetitive stress and two studies proposed poor blood supply as possible etiologies.

Conclusions

We found limited research on histological analysis of OCD lesions of the knee. Future studies with consistent methodology are necessary to draw major conclusions about the histology and progression of OCD lesions. Inconsistent histologic findings have resulted in a lack of consensus regarding the presence of osteonecrosis, whether the necrosis is primary or secondary, the association of cartilage degeneration, and the etiology of OCD. Such studies could use a standardized grading system to allow better comparison of findings.     

Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats

Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular cartilage and subchondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting that treatment timing is a pivotal factor for better effect acquisition.     

The cartilage-bone interface

In the knee joint, the purpose of the cartilage-bone interface is to maintain structural integrity of the osteochondral unit during walking, kneeling, pivoting, and jumping--during which tensile, compressive, and shear forces are transmitted from the viscoelastic articular cartilage layer to the much stiffer mineralized end of the long bone. Mature articular cartilage is integrated with subchondral bone through a approximately 20 to approximately 250 microm thick layer of calcified cartilage. Inside the calcified cartilage layer, perpendicular chondrocyte-derived collagen type II fibers become structurally cemented to collagen type I osteoid deposited by osteoblasts. The mature mineralization front is delineated by a thin approximately 5 microm undulating tidemark structure that forms at the base of articular cartilage. Growth plate cartilage is anchored to epiphyseal bone, sometimes via a thin layer of calcified cartilage and tidemark, while the hypertrophic edge does not form a tidemark and undergoes continual vascular invasion and endochondral ossification (EO) until skeletal maturity upon which the growth plates are fully resorbed and replaced by bone. In this review, the formation of the cartilage-bone interface during skeletal development and cartilage repair, and its structure and composition are presented. Animal models and human anatomical studies show that the tidemark is a dynamic structure that forms within a purely collagen type II-positive and collagen type I-negative hyaline cartilage matrix. Cartilage repair strategies that elicit fibrocartilage, a mixture of collagen type I and type II, are predicted to show little tidemark/calcified cartilage regeneration and to develop a less stable repair tissue-bone interface. The tidemark can be regenerated through a bone marrow-driven growth process of EO near the articular surface.     

A Correlation Exists Between Subchondral Bone Mineral Density of the Distal Radius and Systemic Bone Mineral Density

Background  

Intraarticular distal radius fractures are common and risk articular congruity owing to disruption of the subchondral bone. Studies regarding microstructure and mechanical properties of the distal radius, however, focus only on the cortical and trabecular bones in the metaphysis and not on the subchondral bone.     

Ultrasonographic evaluation of costal cartilage fractures unnoticed by the conventional radiographic study and multidetector computed tomography

Introduction  

Rib fractures are the most common injuries resulting from blunt chest trauma. However, costal cartilage fractures are almost invisible on chest X-rays unless they involve calcified cartilage. The sensitivity of conventional radiography and computed tomography for detecting rib fractures is limited, especially in cases where rib cartilage is involved. Therefore, this study was designed to evaluate the sensitivities of chest wall ultrasonography, clinical findings, and radiography in the detection of costal cartilage fractures.