The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?☆

Qvist, Per; Bay‐Jensen, Anne‐Christine; Christiansen, Claus; Dam, Erik B.; Pastoureau, Philippe; Karsdal, Morten A.

doi:10.1016/j.phrs.2008.06.001

Cited by 144 publications

(115 citation statements)

References 52 publications

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“…Despite the prevalence of OA in the aging population, there are no currently approved DMOADs (22). The analgesic acetaminophen is the first-line therapy indicated for OA treatment and is used for pain management, with no known disease-modifying benefits.…”

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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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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“…These cytokines can stimulate their own production and induce synovial cells and chondrocytes to produce IL-6, IL-8 and leukocyte inhibitory factor, as well as stimulate protease and prostaglandin production (Fernandes et al, 2002). The hypothesis that TNF and IL-1 are key mediators of inflammation and articular cartilage destruction has raised the possibility of anti-cytokine therapy in OA, or the design of specific disease-modifying osteoarthritic drugs (Abramson & Yazici, 2006;Pelletier & Martel-Pelletier, 2005;Berenbaum, 2007;Qvist et al, 2008). If it is accepted that synovial inflammation, and the production of proinflammatory and destructive mediators from the OA synovium, are of importance for the symptoms and progression of osteoarthritis, it is a key question which cell type in the OA synovium is responsible for maintaining synovial inflammation.…”

Section: Introductionmentioning

confidence: 99%

The Role of Synovial Macrophages and Macrophage-Produced Mediators in Driving Inflammatory and Destructive Responses in Osteoarthritis

Bondeson¹,

Wainwright²,

Hughes³

et al. 2012

Principles of Osteoarthritis- Its Definition, Character, Derivation and Modality-Related Recognition

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“…(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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The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?☆

Cited by 144 publications

References 52 publications

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

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

The Role of Synovial Macrophages and Macrophage-Produced Mediators in Driving Inflammatory and Destructive Responses in Osteoarthritis

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

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