The effect of intra-articular glucocorticosteroids and exercise on symptoms and bone marrow lesions in knee osteoarthritis: a secondary analysis of results from a randomized controlled trial

Nielsen, Flemming K.; Boesen, Mikael; Jurik, Anne Grethe; Bliddal, Henning; Nybing, Janus Damm; Ellegaard, Karen; Bartholdy, Cecilie; Bandak, Elisabeth; Henriksen, Marius

doi:10.1016/j.joca.2018.02.900

Cited by 9 publications

(21 citation statements)

References 28 publications

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“…37 Similarly to our study, a randomized controlled superiority trial indicated that an intra-articular injection of 40 mg methylprednisolone plus exercise did not increase the size of knee BML over 26 weeks, and the therapy even decreased the size of knee BML over 14 weeks, compared with placebo plus exercise. 41 While the route of injection of methylprednisolone differs (intra-articular versus intravenous), this combined with our data supports that the administration of methylprednisolone does not have a detrimental effect on the size of osteoarthritis-related BML.…”

Section: Discussionsupporting

confidence: 77%

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

Cai

Laslett

Aitken

et al. 2019

Therapeutic Advances in Musculoskeletal

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Background:The aim of this study was to compare the efficacy and safety of zoledronic acid (ZA) plus intravenous methylprednisolone (VOLT01) to ZA, and placebo for knee osteoarthritis.Methods:A single-center, double-blind, randomized controlled trial (RCT) was carried out. Adults (aged ⩾50 years) with knee osteoarthritis, significant knee pain [⩾40 mm on a 100 mm visual analog scale (VAS)], and magnetic resonance imaging-detected bone marrow lesion (BML) were randomized to receive a one-off administration of VOLT01, ZA, or placebo. The primary hypothesis was that VOLT01 was superior to ZA in having a lower incidence of acute phase responses (APRs) over 3 days. Secondary hypotheses were that VOLT01 was noninferior to ZA, and both treatments were superior to placebo in decreasing BML size over 6 months and in improving knee pain [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and VAS] and function (WOMAC) over 3 and 6 months.Results:A total of 117 patients (62.2 ± 8.1 years, 63 women) were enrolled. The incidence of APRs was similar in the VOLT01 (90%) and ZA (87%) groups (p = 0.74). VOLT01 was superior to ZA in improving knee pain and function after 6 months and noninferior to ZA in reducing BML size. However, BML size change was small in all groups and there were no between-group differences. Compared with placebo, VOLT01 but not ZA improved knee function and showed a trend toward improving knee pain after 6 months.Conclusions:Administering intravenous methylprednisolone with ZA did not reduce APRs or change knee BML size over 6 months, but in contrast to ZA or placebo, it may have a beneficial effect on symptoms in knee osteoarthritis.Trial registration:Australian New Zealand Clinical Trials Registry: ACTRN12613000039785.

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Section: Discussionsupporting

confidence: 77%

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

Cai

Laslett

Aitken

et al. 2019

Therapeutic Advances in Musculoskeletal

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“…To date, intra‐articular delivery has been a widely accepted therapeutic method for the treatment of OA. In addition to the traditional drugs such as corticosteroids and hyaluronic acid (Nielsen et al, 2018; Smith et al, 2019), researchers are developing new drugs with anti‐inflammatory and cartilage‐protective functions (Alves et al, 2020; Garza et al, 2020; Nemirov et al, 2020), and as part of this development, circRNA injection has been used in some OA animal models. Our previous study (Zhou et al, 2019) showed that circRNA.33186, which was significantly upregulated in in vivo and in vitro OA mouse model, regulated ECM catabolism and chondrocyte apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…To date, intra-articular delivery has been a widely accepted therapeutic method for the treatment of OA. In addition to the traditional drugs such as corticosteroids and hyaluronic acid (Nielsen et al, 2018;Smith et al, 2019) OA animal models. Our previous study (Zhou et al, 2019) showed that circRNA.33186, which was significantly upregulated in in vivo and in vitro OA mouse model, regulated ECM catabolism and chondrocyte apoptosis.…”

Section: Mir-296-3p Directly Targets Ptenmentioning

confidence: 99%

Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR‐296‐3p/PTEN axis

Zhou

et al. 2020

Journal Cellular Physiology

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Circular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain‐of‐function and loss‐of‐function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR‐296‐3p and miR‐296‐3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno‐associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)‐induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR‐296‐3p and regulating the miR‐296‐3p‐PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM‐induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR‐296‐3p‐PTEN pathway. It provides a potential target for developing effective interventions in treating OA.

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“…К 26 неделе различия были нивелированы (0,8%, p = 0,65]. Авторы сделали заключение, что эти результаты -доказательство малой силы наличия зависимости между внутрисуставным применением глюкокортикостероидов и динамикой ОКМ [39]. Регулярное внутрисуставное введение триамцинолона или плацебо раз в три месяца на протяжении двух лет (8 инъекций) у 140 пациентов приводило к значительно большей потере объема хряща в группе триамцинолона (-0,21 мм), чем в группе физиологического раствора (-0,1 мм) при отсутствии различий по влиянию на суставную боль [40].…”

Section: влияние консервативной терапии на отек костного мозгаunclassified

Clinical significance of bone marrow edema in the late stages of osteoarthritis

2020

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The use of magnetic resonance imaging (MRI) for osteoarthritis made it possible to simultaneously detail the state of cartilage, subchondral bone, menisci, ligaments, and synovial membrane. In some studies, a correlation was found between bone marrow edema (BME) and the intensity of the pain syndrome, the progression of OA and the risk of total knee replacement. In other studies, these data were not confirmed. It has been suggested that BME in OA, leading to debilitating pain, is not associated with trauma and is determined by an increase in extracellular fluid. Analysis of MRI images of 80 patients with 1-3 stages of knee osteoarthritis revealed a statistically significant relationship between the presence of bone marrow edema and the thickness of the cartilage of the femur and tibia, rupture and degradation of the medial menisci, the presence of Baker cysts and thickening of the synovial membrane. No reliable relationship was found with the presence and severity of synovitis. A review of data on the effect of various methods of conservative therapy on bone marrow edema in osteoarthritis is presented. The effect of anti-osteoporotic drugs, prostacyclin, Pentosan polysulfate sodium chondroitin sulfate is considered. Thus, OKM is of interest both in terms of the pathogenesis of OA and as an indicator of the effectiveness of the treatment of OA. Our data demonstrate a high incidence of OKM in the late stages of OA. The effect of pharmacological therapies on OKM requires further study.

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The effect of intra-articular glucocorticosteroids and exercise on symptoms and bone marrow lesions in knee osteoarthritis: a secondary analysis of results from a randomized controlled trial

Abstract: EudraCT number: 2012-002607-18.

Cited by 9 publications

References 28 publications

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR‐296‐3p/PTEN axis

Clinical significance of bone marrow edema in the late stages of osteoarthritis

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