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

Hayami, Tadashi; Pickarski, Maureen; Zhuo, Ya; Wesolowski, Gregg; Rodan, Gideon A.; Duong, Le T.

doi:10.1016/j.bone.2005.08.007

Cited by 540 publications

(549 citation statements)

References 35 publications

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“…In a guinea pig model, bone densitometry evaluation following meniscectomy revealed typical variations in bone metabolism with early resorption of subchondral bone followed by increased bone density [18]. This concurs with findings from other animal models, such as the ACL dog and rat OA models, in which were observed, at an early stage of the disease process, increased subchondral bone resorption with trabecular thickness reduction and an increased number of osteoclasts, as well as increased production of catabolic factors including cathepsin K and matrix metalloproteinase (MMP)-13 [6][7][8][9].…”

Section: Correlation Between In Vivo Findings In Animals and Human Oasupporting

confidence: 83%

“…Moreover, in this animal model, the severity of cartilage fibrillation and loss generally exceeds bone changes only in advanced OA. Although it has been shown in some induced OA animal models, which allow chronological analysis of the disease progression, that the subchondral bone changes precede cartilage changes [6][7][8][9], this has yet to be clarified in humans.…”

Section: Osteoarthritismentioning

confidence: 99%

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Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

153

121

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Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

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Section: Correlation Between In Vivo Findings In Animals and Human Oasupporting

confidence: 83%

Section: Osteoarthritismentioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

153

121

View full text Add to dashboard Cite

show abstract

“…The analgesic acetaminophen is the first-line therapy indicated for OA treatment and is used for pain management, with no known disease-modifying benefits. Several bisphosphonate drugs have previously been shown to have disease-modifying treatment outcomes in OA in animal models (23)(24)(25) and humans (26)(27)(28). However, those studies had contradictory results regarding the disease-modifying efficacy of bisphosphonate drugs, particularly since most studies in humans involved patients with end-stage OA, rather than individuals at an earlier stage of OA pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Jones

Tran

et al. 2010

Arthritis & Rheumatism

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Objective. To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).Methods. We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.Results. Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicamtreated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury.Conclusion. Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.

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“…Animal studies have also indicated that bone resorption inhibitors suppress OA progression. (4,5) Several bone turnoverinhibiting drugs, such as alendronate, risedronate, and calcitonin, have been proposed as candidates for OA treatment. (6,7) Therefore, it is important to understand subchondral bone turnover to analyze OA pathophysiology and develop appropriate therapies.…”

Section: Introductionmentioning

confidence: 99%

Relationship between microstructure and degree of mineralization in subchondral bone of osteoarthritis: A synchrotron radiation µCT study

Chiba

Nango²,

Kubota³

et al. 2012

Journal of Bone and Mineral Research

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We analyzed the microstructure and degree of mineralization of the subchondral trabecular bone in hip osteoarthritis (OA) using synchrotron radiation computed tomography (SRCT) to identify the relationship between bone structure and bone turnover. Subchondral bone samples were extracted from femoral heads of 10 terminal-staged hip OA patients. The SRCT scan was performed at 30 keV energy and 5.9 mm voxel size. Trabecular bone structure, bone cyst volume, and the degree of trabecular bone mineralization were measured, and correlations between bone structure and the degree of mineralization were analyzed. In addition, the trabecular bone was divided into the area immediately surrounding the bone cyst and the remaining area, and they were compared. The average cyst volume fraction in the whole region was 31.8%, and the bone volume fraction in the bone region was 55.6%. Cyst volume was the only structural parameter that had a significant correlation with the degree of mineralization. The degree of mineralization was diminished when the bone cyst was larger (r ¼ À0.81, p ¼ 0.004). The trabecular bone immediately surrounding the bone cyst had a lower degree of mineralization when compared with the remaining trabecular bone (p ¼ 0.008). In the bone sclerosis of OA subchondral bone, there are many large and small bone cysts, which are expected to play a significant part in the high bone turnover of OA. ß

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

Cited by 540 publications

References 35 publications

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Relationship between microstructure and degree of mineralization in subchondral bone of osteoarthritis: A synchrotron radiation µCT study

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