Dataset Information

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

ABSTRACT:

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 ?g/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.

SUBMITTER: Yu DG

PROVIDER: S-EPMC4011147 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Yu De-gang DG Yu Bo B Mao Yuan-qing YQ Zhao Xin X Wang Xiao-qing XQ Ding Hui-feng HF Cao Lei L Liu Guang-wang GW Nie Shao-bo SB Liu Shen S Zhu Zhen-an ZA

Acta pharmacologica Sinica 20120521 7

<h4>Aim</h4>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.<h4>Methods</h4>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 evalua ...[more]

PMID: 22609837

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Project description:Background and purpose - No consensus exists on when to perform arthroscopic partial meniscectomy in patients with a degenerative meniscal tear. Since MRI and clinical tests are not accurate in detecting a symptomatic meniscal lesion, the patient's symptoms often play a large role when deciding when to perform surgery. We determined the prevalence and severity of self-reported knee symptoms in patients eligible for arthroscopic partial meniscectomy due to a degenerative meniscal tear. We investigated whether symptoms commonly considered to be related to meniscus injury were associated with early radiographic signs of knee osteoarthritis. Patients and methods - We included individual baseline items from the Knee injury and Osteoarthritis Outcome Score collected in 2 randomized controlled trials evaluating treatment for an MRI-verified degenerative medial meniscal tears in 199 patients aged 35-65 years. Each item was scored as no, mild, moderate, severe, extreme, and at least "mild" considering the symptoms present. Early radiographic signs of osteoarthritis, defined as a Kellgren and Lawrence grade of at least 1, were seen in 70 patients. Results - At least monthly knee pain, pain during stair walking and when twisting on the knee, and lack of confidence in knee was present in at least 80% of the patients. Median severity was at least moderate for knee pain, pain when twisting on the knee, pain walking on stairs, lack of confidence in knee, and clicking. Mechanical symptoms such as catching were rare. Early radiographic signs of osteoarthritis were associated with an increased risk of self-reported swelling, catching, and stiffness later in the day; the odds ratio was 2.4 (95% CI 1.2-4.9), 2.3 (1.2-4.3), and 2.3 (1.1-5.0), respectively. Interpretation - Middle-aged patients with a degenerative medial meniscus tear reported symptoms commonly associated with knee osteoarthritis. Frequent knee pain, presence of lack of confidence in the knee, and clicking did not distinguish those with a meniscal tear alone from those with early radiographic knee OA. Our findings support the notion that symptoms reported by those with a degenerative meniscal tear represent early signs of knee osteoarthritis.

Dataset Information

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

Aim

Methods

Results

Conclusion

Publications

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

Similar Datasets

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