Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort

Mazières, B; Garnero, Patrick; Guéguen, A.; Abbal, M.; Berdah, L.; Lequesne, M; Nguyen, Minh Vu Chuong; Salles, Jean‐Pierre; Vignon, E.; Dougados, Maxime

doi:10.1136/ard.2005.037275

Cited by 104 publications

(92 citation statements)

References 34 publications

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“…This observation was consistent with previous reports (19)(20)(21)26,28). Because urinary CTX-II levels reflect the degradation of cartilage type II collagen in all body joints, including the * The odds ratio (OR) was adjusted for sex, age, and body mass index.…”

Section: Discussionsupporting

confidence: 89%

“…Because the levels of bone markers in serum or urine mainly reflect the overall rate of skeletal turnover, which can be affected by different conditions independent of OA, they are likely to lack sensitivity to detect focal abnormalities of subchondral bone metabolism, a factor that may explain the inconsistent and somewhat disappointing data generated between markers of bone turnover and joint damage in OA (3,4). In contrast, several studies have shown a consistent association between increased baseline levels of urinary CTX-II and more rapid progression of radiographic knee or hip OA over the subsequent 1-6 years (19)(20)(21). Additionally, we previously showed that decreased urinary CTX-II levels over 3 months in patients with early rheumatoid arthritis who were treated with an active combination of prednisolone, methotrexate, and sulfasalazine were associated with slower radiographic progression over the subsequent 5 years (30), suggesting that early changes in this marker may be related to long-term progression, although this hypothesis needs to be confirmed in OA.…”

Section: Discussionmentioning

confidence: 99%

“…Among these, urinary excretion of specific fragments of C-terminal crosslinking telopeptide of type II collagen (CTX-II) has been shown to be associated with progression of joint damage in OA (19)(20)(21). However, no study has yet investigated the relationship between these imaging and molecular markers in OA, particularly longitudinally.…”

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confidence: 99%

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Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

Garnero¹,

Peterfy²,

Zaim³

et al. 2005

Arthritis & Rheumatism

145

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Objective. Using radiography to assess the efficacy of a disease-modifying osteoarthritis (OA) drug on joint structure is challenging. Subchondral bone marrow abnormalities determined by magnetic resonance imaging (MRI) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) have recently been shown to be predictors of radiographic progression in patients with knee OA, suggesting that these may represent valuable biomarkers with increased sensitivity compared with findings on radiography. The aims of this investigation were to analyze, in patients with knee OA, whether the values associated with these 2 OA biomarkers can change within 3 months, and to investigate the relationships between bone marrow abnormalities and CTX-II.Methods. Knee MRI scans were obtained in 377 patients with painful knee OA (76% women, mean age 63 years, mean disease duration 6.6 years) at both baseline and 3 months. The femoral and tibial condyles and the patella were divided into 8 sites for the scoring of bone marrow abnormalities. A bone marrow abnormality was defined as an area of increased signal on T2-weighted images of the subchondral bone. All scans were reviewed centrally and scored by a single trained radiologist using a validated 4-point scoring method. Fasting urine and serum samples were also collected from all patients at baseline, month 1, month 2, and month 3, in order to measure the levels of urinary CTX-II and serum CTX-I, a biochemical marker of bone resorption.Results. At baseline, 82% of patients had MRI evidence of bone marrow abnormalities. Bone marrow abnormality scores correlated significantly with CTX-II levels (P < 0.0001). Within 3 months, the bone marrow abnormality score decreased in 37 patients (9.8%), increased in 71 patients (18.8%), and did not change in the majority of patients (71.4%). Patients with baseline urinary CTX-II levels in the highest tertile had a relative risk of 2.4 (95% confidence interval 1.1-5.0) of worsening bone marrow abnormalities at 3 months compared with patients with levels in the lowest tertile, after adjustment for age, sex, and body mass index. In patients who showed a decrease in the bone marrow abnormality score at 3 months, urinary CTX-II levels decreased significantly (mean ؊75 ng/mmole creatinine), whereas levels increased (mean ؉23 ng/mmole creatinine) in patients showing an increase in the bone marrow abnormality score (P ‫؍‬ 0.01 between the 2 groups). No significant association between bone marrow abnormalities and serum CTX-I was observed.Conclusion. In patients with painful knee OA, bone marrow abnormalities on MRI can change within only 3 months in ϳ30% of patients. Reduction in the extent of bone marrow abnormalities is associated with a decrease in cartilage degradation.Osteoarthritis (OA) of the knee frequently affects the elderly population and is characterized by cartilage loss, osteophytes, and subchondral sclerosis and cysts (1). Radiography is currently the only method accepted by regulatory agencies for assessing progress...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

Garnero¹,

Peterfy²,

Zaim³

et al. 2005

Arthritis & Rheumatism

145

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“…Recently, various biomarkers have been developed to detect the articular alterations in OA (49,50), and there are accumulating data supporting the association of the changes in various CII degradation biomarkers, such as CTX-II, C1, 2C and C2C (51)(52)(53), and a synovial inflammation biomarker HA (54,55) with the disease progression in knee OA. In the present study, we utilized C2C and HA for evaluating the effects of the test supplement on the pathophysiological changes in the cartilage and synovium, respectively, as described previously (56). The results demonstrated that the serum levels of both C2C and HA time-dependently decreased only in the test group.…”

Section: Discussionmentioning

confidence: 82%

Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study

Nakasone¹,

Watabe²,

Watanabe³

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. In the present study, we aimed to investigate the potential effect of a glucosamine (1,200 mg/day)-based dietary supplement combined with chondroitin sulfate and three antioxidant micronutrients, namely methylsulfonylmethane, guava leaf extract, and vitamin D (test supplement) on osteoarthritis (OA) of the knee. A 16-week, randomized, double-blinded, placebo-controlled trial was conducted involving 32 subjects with symptomatic knee OA. Clinical outcomes were measured using the Japanese Knee Osteoarthritis Measure (JKOM) for symptoms and a study diary-based visual analog scale (diary VAS) for pain at baseline and at weeks 4, 8, 12 and 16 during the 16-week intervention period. Furthermore, biomarkers for cartilage type II collagen degradation (C2C) and synovitis hyaluronan (HA) were measured. As compared with the baseline, the JKOM pain subscale was significantly improved at all of the four assessment time points in the test group, but was not at any time point in the placebo group. On the other hand, all of the four symptom subscales and the aggregated total symptoms were significantly improved in the two groups at one or more time points. However, all of these clinical improvements were greater in extent in the test group than in the placebo group, and there were significant differences between groups in the magnitude of changes from baseline for one subscale 'general activities' and the aggregated total symptoms at week 8 (P<0.05). The results of efficacy assessments with the diary VAS showed that all of the three pain subscales were significantly improved only in the test group at almost all the time points. Moreover, serum levels of C2C and HA were decreased by 10 and 25%, respectively, at week 16 in the test group, albeit not statistically significant, without any detectable changes in the placebo group. In conclusion, although the results obtained in this study were not conclusive, the tested glucosamine-based combination supplement is likely to have a beneficial effect on pain and other symptoms associated with knee OA.

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“…These 2 markers have been used in human studies and are shown to be indicative of various aspects of OA. HA is a glycosaminoglycan found in synovium and cartilage that predicts disease outcome in knee (39) and hip OA (40) and correlates with OA progression (39)(40)(41)(42)(43)(44)(45). To date, there are few data regarding serum or synovial fluid biomarker levels following articular fracture and the subsequent development of arthritis.…”

mentioning

confidence: 99%

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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Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort

Cited by 104 publications

References 34 publications

Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study

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

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