Should subchondral bone turnover be targeted when treating osteoarthritis?

Karsdal, Morten A.; Leeming, Diana Julie; Dam, Erik B.; Henriksen, Kim; Alexandersen, Peter; Pastoureau, Philippe; Altman, Roy D.; Christiansen, Claus

doi:10.1016/j.joca.2008.01.014

Cited by 190 publications

(151 citation statements)

References 103 publications

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“…(37) The tidemark, which was thought previously to be a strict barrier between cartilage and bone, allows perfusion of chemo-and cytokines released by the diseased chondrocytes and inflamed synovial tissue. (38) In line with this assumption is that if mechanics instead of chemical components would be involved, a compensatory increase in bone tissue is anticipated owing to the loss of the mechanical function and with that shock absorbance of the cartilage.…”

Section: Discussionmentioning

confidence: 99%

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

Intema

Sniekers

Weinans

et al. 2010

Journal of Bone and Mineral Research

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In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C-telopeptide of type II collagen (CTX-II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro-computed tomography (mCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTX-II levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint. ß

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Section: Discussionmentioning

confidence: 99%

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

Intema

Sniekers

Weinans

et al. 2010

Journal of Bone and Mineral Research

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“…However, it is increasingly accepted that subchondral bone plays an important role in the pathogenesis of OA. Accumulating evidence from clinical and animal studies has demonstrated that during OA progression, subchondral bone turnover increases dramatically, with increased bone resorption occurring early, and increased bone accretion occurring later in the disease [6][7][8] . Meanwhile, the biochemical composition and biomechanical properties of the subchondral bone are altered [9,10] .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Mao

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. Methods: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 μg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. Results: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. Conclusion: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

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“…The increased stress thereby imposed on the other components of the joint complex usually triggers a process of tissue remodeling, which, by altering the loading dynamics of the joint, exacerbates rather than alleviates the disease symptoms [18,21]. Furthermore, the pain and restricted ROM associated with OA necessitate changes in the pattern of loading by the affected individual, which further complicate the development of the disease.…”

Section: Introductionmentioning

confidence: 99%

Stereologic Analysis of Tibial-Plateau Cartilage and Femoral Cancellous Bone in Guinea Pigs With Spontaneous Osteoarthritis

Wang

Arsenault

Hunziker

2011

Clinical Orthopaedics &Amp; Related Research

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Background Two strains of guinea pig develop spontaneous osteoarthritis of the knee. Although the disease evolves at different rates in the two strains, it is not known whether these differences are reflected in the structure of the cartilage and cancellous bone. Questions/purposes We determined whether the threedimensional structure of the tibial-plateau cartilage and femoral cancellous bone differed between the two strains. Methods Six Dunkin-Hartley and six GOHI/SPF guinea pigs were evaluated. The animals were sacrificed at 11 months of age. The 24 proximal tibias were used for a stereologic histomorphometric analysis of the tibial-plateau cartilage. The 24 femurs were used for a site-specific, three-dimensional quantitative analysis of the cancellous bone by micro-CT. Results Compared to the GOHI/SPF guinea pigs, the tibial-plateau cartilage of the Dunkin-Hartley strain had a larger lesion volume (3.8% versus 1.5%) and a thicker uncalcified cartilage layer (0.042 versus 0.035 mm), but a thinner calcified cartilage zone (0.008 versus 0.01 mm) and a thinner subchondral cortical bone plate (0.035 versus 0.039 mm). The femoral cancellous bone in the DunkinHartley strain had a lower bone mineral density (477 versus 509 mg/cm 3 ). However, the trabeculae were thicker (3.91 versus 3.53 pixels) and farther apart (7.8 versus 5.6 pixels). The osteoarthritic changes in the cartilage were topographically mirrored in the subchondral bone. They were most severe on the medial side of the joint, particularly in the anterior region. Conclusions Spontaneous osteoarthritis in the guinea pig is associated with site-specific changes in the articular cartilage layer, which are topographically mirrored in the underlying subchondral bone. Clinical Relevance Three-dimensional structural information not revealed by two-dimensional radiography may help characterize the stages of osteoarthritis.

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Should subchondral bone turnover be targeted when treating osteoarthritis?

Cited by 190 publications

References 103 publications

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Stereologic Analysis of Tibial-Plateau Cartilage and Femoral Cancellous Bone in Guinea Pigs With Spontaneous Osteoarthritis

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