Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis

Background: Receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) are pivotal molecules involved in osteoclast activation and resorption. In RA, their alterations mediated through inflammatory cytokines are responsible for erosions and systemic bone loss. This study planne...

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Main Authors: Aadhaar Dhooria, Narendhiran Pandurangan, Karthik Vinay Mahesh, Suchet Sachdev, Aman Sharma, Shefali Sharma, Nidhi Gupta, Varun Dhir
Format: Article
Language:English
Published: SAGE Publishing 2018-01-01
Series:Indian Journal of Rheumatology
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Online Access:http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2018;volume=13;issue=2;spage=90;epage=94;aulast=Dhooria
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author Aadhaar Dhooria
Narendhiran Pandurangan
Karthik Vinay Mahesh
Suchet Sachdev
Aman Sharma
Shefali Sharma
Nidhi Gupta
Varun Dhir
author_facet Aadhaar Dhooria
Narendhiran Pandurangan
Karthik Vinay Mahesh
Suchet Sachdev
Aman Sharma
Shefali Sharma
Nidhi Gupta
Varun Dhir
author_sort Aadhaar Dhooria
collection DOAJ
description Background: Receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) are pivotal molecules involved in osteoclast activation and resorption. In RA, their alterations mediated through inflammatory cytokines are responsible for erosions and systemic bone loss. This study planned to look at the effect of methotrexate on circulating levels of OPG and RANKL in RA. Methods: Methotrexate-naive patients with active rheumatoid arthritis (RA) between 18 and 65 years of age were included. Controls were derived from voluntary healthy blood donors after written consent. All patients were started on methotrexate at 15 mg/week, increased by 5 mg every 4 weeks till maximum tolerated dose or 25 mg/week whichever was lower. Circulating plasma levels of OPG and RANKL were measured for cases (at baseline and 24 weeks) and controls (at baseline). Results: Fifty-one consecutive patients with RA and 57 controls were recruited. Circulating OPG (mean ± standard deviation) levels were higher in RA patients as compared to controls, 2879.6 ± 1037.9 and 2214.1 ± 705.3 pg/ml, respectively (P < 0.001). RANKL levels did not differ significantly between cases and controls. After treatment, circulating OPG levels fell significantly, from 2879.6 ± 1037.9 to 2059.8 ± 532.1 pg/ml (P < 0.001), however, no significant change in circulating RANKL levels. No difference was found in OPG and RANKL levels between patients with erosive and nonerosive disease. Conclusions: OPG levels are higher in RA patients and normalize in response to treatment with methotrexate. The initial higher levels of OPG may represent a compensatory mechanism to osteoclast activation; they normalize on reduction of disease activity.
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spelling doaj-art-184177294ee24ce5aca584ef25d4d51b2025-01-03T01:45:39ZengSAGE PublishingIndian Journal of Rheumatology0973-36980973-37012018-01-01132909410.4103/injr.injr_125_17Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritisAadhaar DhooriaNarendhiran PanduranganKarthik Vinay MaheshSuchet SachdevAman SharmaShefali SharmaNidhi GuptaVarun DhirBackground: Receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) are pivotal molecules involved in osteoclast activation and resorption. In RA, their alterations mediated through inflammatory cytokines are responsible for erosions and systemic bone loss. This study planned to look at the effect of methotrexate on circulating levels of OPG and RANKL in RA. Methods: Methotrexate-naive patients with active rheumatoid arthritis (RA) between 18 and 65 years of age were included. Controls were derived from voluntary healthy blood donors after written consent. All patients were started on methotrexate at 15 mg/week, increased by 5 mg every 4 weeks till maximum tolerated dose or 25 mg/week whichever was lower. Circulating plasma levels of OPG and RANKL were measured for cases (at baseline and 24 weeks) and controls (at baseline). Results: Fifty-one consecutive patients with RA and 57 controls were recruited. Circulating OPG (mean ± standard deviation) levels were higher in RA patients as compared to controls, 2879.6 ± 1037.9 and 2214.1 ± 705.3 pg/ml, respectively (P < 0.001). RANKL levels did not differ significantly between cases and controls. After treatment, circulating OPG levels fell significantly, from 2879.6 ± 1037.9 to 2059.8 ± 532.1 pg/ml (P < 0.001), however, no significant change in circulating RANKL levels. No difference was found in OPG and RANKL levels between patients with erosive and nonerosive disease. Conclusions: OPG levels are higher in RA patients and normalize in response to treatment with methotrexate. The initial higher levels of OPG may represent a compensatory mechanism to osteoclast activation; they normalize on reduction of disease activity.http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2018;volume=13;issue=2;spage=90;epage=94;aulast=DhooriaMethotrexateosteoprotegerinreceptor activator of nuclear factor κβ ligandrheumatoid arthritis
spellingShingle Aadhaar Dhooria
Narendhiran Pandurangan
Karthik Vinay Mahesh
Suchet Sachdev
Aman Sharma
Shefali Sharma
Nidhi Gupta
Varun Dhir
Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
Indian Journal of Rheumatology
Methotrexate
osteoprotegerin
receptor activator of nuclear factor κβ ligand
rheumatoid arthritis
title Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
title_full Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
title_fullStr Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
title_full_unstemmed Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
title_short Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis
title_sort circulating levels of osteoprotegerin and srankl and the effect of methotrexate in patients with rheumatoid arthritis
topic Methotrexate
osteoprotegerin
receptor activator of nuclear factor κβ ligand
rheumatoid arthritis
url http://www.indianjrheumatol.com/article.asp?issn=0973-3698;year=2018;volume=13;issue=2;spage=90;epage=94;aulast=Dhooria
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