Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography

Boyd, Steven K.; Müller, Ralph; Matyas, John R.; Wohl, Gregory R.; Zernicke, Ronald F.

doi:10.1016/s0268-0033(00)00023-1

Cited by 57 publications

(62 citation statements)

References 32 publications

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“…A decrease in trabecular bone thickness and a loss of bone density has been shown in OA (35). The C57BL/6 mice in this study had a decrease in bone density in the fractured limb compared with the control limb at 4 and 8 weeks postfracture, which is consistent with OA changes previously reported clinically (35,36) and in animal models (7,37,38). However, the MRL/MpJ mice did not show a decrease in bone density in the fractured limb as compared with the control limb in the metaphyseal region of the tibia.…”

Section: Discussionsupporting

confidence: 90%

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Ward¹,

Furman²,

Huebner³

et al. 2008

Arthritis & Rheumatism

112

127

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Objective. Posttraumatic arthritis is a frequent long-term complication of intraarticular fractures. A model of a closed intraarticular fracture in C57BL/6 mice that progresses to posttraumatic arthritis has been developed. The MRL/MpJ mouse has shown unique regenerative abilities in response to injury. The objective of this study was to determine if the MRL/MpJ mouse is protected from posttraumatic arthritis after intraarticular fractures.Methods. Intraarticular fractures were created in MRL/MpJ mice and C57BL/6 control mice (n ‫؍‬ 16 each). Limbs were analyzed for posttraumatic arthritis 4 and 8 weeks after fracture using microfocal computed tomography bone morphology, subchondral bone thickness evaluation, and histologic evaluation of cartilage degeneration. Serum cytokines and biomarkers were measured after the mice were killed.Results. Intraarticular fractures were successfully created in all 32 mice. In the experimental fractured limbs, C57BL/6 mice had a decrease in bone density, increased subchondral bone thickness, and increased cartilage degeneration compared with normal contralateral control limbs. In the MRL/MpJ mice, no differences in bone density, subchondral bone thickness, or histologic grading of cartilage degeneration were seen between fractured and contralateral control limbs. Cytokine analysis showed lower systemic levels of the proinflammatory cytokine interleukin-1␣ (IL-1␣) and higher levels of the antiinflammatory cytokines IL-4 and IL-10 in the MRL/MpJ mice.Conclusion. This study shows that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis after intraarticular fracture. Further investigation into the mechanism involved in this response will hopefully provide new insight into the pathogenesis, prevention, and treatment of posttraumatic arthritis after intraarticular fracture.

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Section: Discussionsupporting

confidence: 90%

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Ward¹,

Furman²,

Huebner³

et al. 2008

Arthritis & Rheumatism

112

127

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“…The extent of pathology of the experimental joint tissues was characteristic for this model at these time intervals, including articular cartilage hypertrophy (18), chondroosteophyte development (27), subchondral bone remodeling (28,29), and degeneration of the medial menisci (19). In all dogs, except for the excluded animal, the contralateral control joints appeared normal (morphology score 0).…”

Section: Resultsmentioning

confidence: 97%

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Matyas

Atley

Ionescu

et al. 2004

Arthritis & Rheumatism

140

124

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Objective. To study 3 body fluids for changes in the levels of 5 biomarkers of cartilage metabolism during the early phases of experimental osteoarthritis (OA).Methods. Twenty skeletally mature mixed-breed canines underwent unilateral surgical transection of the anterior cruciate ligament. Samples of joint fluid, serum, and urine were obtained preoperatively and just before necropsy (3 weeks or 12 weeks postoperatively). Biomarkers included 2 markers of cartilage matrix synthesis/turnover (aggrecan 846 epitope and C-propeptide of type II collagen) and 3 markers of cartilage degradation (keratan sulfate proteoglycan epitope, the collagenase-generated cleavage epitope of type II collagen [Col2-3/4C long mono , or CIIC], and crosslinked peptides from the C-telopeptide domain of type II collagen [Col2CTx]). Significant changes in the levels of these biomarkers were determined by paired analyses.Results. Joint pathology was more severe in the 12-week group compared with the 3-week group. In joint fluid, due to limited volume, only Col2-3/4C long mono and Col2CTx were measured. Significant elevations in the levels of both of these markers were observed in experimental joints in both the 3-week group and the 12-week group. In serum, the level of aggrecan 846 epitope was elevated at both 3 weeks and 12 weeks, the level of Col2-3/4C long mono was elevated at 12 weeks, and the level of Col2CTx was elevated at both 3 weeks and 12 weeks. In urine, the level of Col2-3/4C long mono was elevated at 12 weeks after surgery.Conclusion. Levels of biomarkers of intact aggrecan proteoglycan (aggrecan 846 epitope) and type II collagen degradation (Col2-3/4C long mono and Col2CTx) were elevated early after unilateral stifle joint injury, suggesting that these markers are sensitive and specific for early cartilage changes associated with isolated joint injury in this established model of experimental OA.The early stages of osteoarthritis (OA) are difficult to diagnose. Joint structure and function are typically altered substantially before symptoms cause patients to seek medical care, that is, the osteoarthritic process begins long before OA presents as a clinical disease. The insidious onset and "silent" progression of primary OA not only obscure an early diagnosis, but also delay treatment that may help prevent further cartilage destruction and joint failure. Hence, diagnostic tests that can detect and monitor molecular events early in the pathogenesis of OA would be potentially very useful.For nearly a century, synovial fluid analysis has been important in the differential diagnosis of arthritis. Although synovial fluid analysis is useful in distinguishing between inflammatory, septic, and crystal-induced arthritis, its value in OA is limited. Similarly, routine blood and urine analyses can identify certain inflammatory arthritides and metabolic defects that cause joint pain and pathology but, as yet, reveal little about the OA process. No specific molecular markers of the OA process are currently available for clinical use, and the...

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“…For example, in an experimental model of osteoarthritis, clinical CT was able to detect a large decrease in bone fractional volume (40%) following a knee joint injury [20]; however, the exact morphologic changes that occurred could not be determined from those low-resolution data. Subsequently, in the same bones, micro-CT was able to quantify the precise morphologic changes underlying those data [21], and through the combined use of specifically designed mechanical testing methods with finite element modeling, it was possible to provide insight into the pathogenesis of this experimental model. As an example, it was established that despite the large morphologic changes, there were no associated detectable changes in bone tissue properties [14], thus indicating that architectural changes played a primary role in the early pathogenesis of osteoarthritis.…”

Section: Sensitivity Of Micro-ct To Quantify Changes In Trabecular Momentioning

confidence: 99%

Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue

Judex

Boyd²,

Qin³

et al. 2003

Curr Osteoporos Rep

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Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.

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Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography

Cited by 57 publications

References 32 publications

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue

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