Role of Bone in Knee Osteoarthritis (OA)

NCT ID: NCT00850538

Last Updated: 2015-12-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

101 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-07-31

Study Completion Date

2013-04-30

Brief Summary

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The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. Connective tissues including tendon, ligament, and meniscus specimens normally discarded from total joint replacements will be used for live cell harvest, and protein and gene expression analyses of tissue or cultured cells.

Detailed Description

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BACKGROUND AND SIGNIFICANCE:

Although the presence of bone marrow lesions (BML) on MRI is strongly associated with osteoarthritis (OA) progression and pain in some studies, the mechanism for this relation and the underlying pathology is not well established. The lack of knowledge on what these lesions constitute hampers their clinical utility both with regards to measurement and targeting for therapeutic intervention.

Our preliminary data has localized specific changes in bone mineralization, remodeling and defects within BML features that are adjacent to the subchondral plate. BMLs appear to be sclerotic compared to unaffected regions; however, the mineral density in these lesions is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition. Limited histological analysis of BMLs reveal thrombi, diffuse fibrinoid necrosis and hyperplasia of blood vessel walls - all indicative of infarction-like pathology.

The aim of this research proposal is to create more specific targets and improve our understanding of the pathology in BMLs.

Specific Aim 1:

\- To collect tissue to evaluate protein and gene expression of these tissues and cultured cells.

Conditions

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Osteoarthritis, Knee

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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MRI

1.5T MRI exam of signal knee with knee coil (estimated time: 35 minutes)

Intervention Type RADIATION

Primary Total Knee Replacement

Fluid, bone, and meniscus specimens obtained from total joint replacement will be collected.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* subjects having primary knee replacement surgery with 1 participating surgeon at NEBH (principal investigator)

Exclusion Criteria

* subjects having a revision knee replacement instead of a primary knee replacement
* contraindications for MRI
* pregnancy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The New England Baptist Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Hunter

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Hunter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Sydney

Locations

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University of Sydney

Sydney, New South Wales, Australia

Site Status

Countries

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Australia

References

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Burr DB. The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 2004 Apr;70:77-80. No abstract available.

Reference Type BACKGROUND
PMID: 15132360 (View on PubMed)

Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, Kazis L, Gale DR. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001 Apr 3;134(7):541-9. doi: 10.7326/0003-4819-134-7-200104030-00007.

Reference Type BACKGROUND
PMID: 11281736 (View on PubMed)

Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, Li W, Hill C, Gale D. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med. 2003 Sep 2;139(5 Pt 1):330-6. doi: 10.7326/0003-4819-139-5_part_1-200309020-00008.

Reference Type BACKGROUND
PMID: 12965941 (View on PubMed)

Lo GH, Hunter DJ, Zhang Y, McLennan CE, Lavalley MP, Kiel DP, McLean RR, Genant HK, Guermazi A, Felson DT. Bone marrow lesions in the knee are associated with increased local bone density. Arthritis Rheum. 2005 Sep;52(9):2814-21. doi: 10.1002/art.21290.

Reference Type BACKGROUND
PMID: 16145676 (View on PubMed)

Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, Guermazi A, Genant H, Gale D, Felson DT. Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum. 2006 May;54(5):1529-35. doi: 10.1002/art.21789.

Reference Type BACKGROUND
PMID: 16646037 (View on PubMed)

Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000 Jun;215(3):835-40. doi: 10.1148/radiology.215.3.r00jn05835.

Reference Type BACKGROUND
PMID: 10831707 (View on PubMed)

Neuhold A, Hofmann S, Engel A, Leder K, Kramer J, Haller J, Plenk H. Bone marrow edema of the hip: MR findings after core decompression. J Comput Assist Tomogr. 1992 Nov-Dec;16(6):951-5. doi: 10.1097/00004728-199211000-00023.

Reference Type BACKGROUND
PMID: 1430447 (View on PubMed)

Plenk H Jr, Hofmann S, Eschberger J, Gstettner M, Kramer J, Schneider W, Engel A. Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip. Clin Orthop Relat Res. 1997 Jan;(334):73-84.

Reference Type BACKGROUND
PMID: 9005898 (View on PubMed)

Reinus WR, Fischer KC, Ritter JH. Painful transient tibial edema. Radiology. 1994 Jul;192(1):195-9. doi: 10.1148/radiology.192.1.8208937.

Reference Type BACKGROUND
PMID: 8208937 (View on PubMed)

Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis. 2008 Feb;67(2):206-11. doi: 10.1136/ard.2006.066183. Epub 2007 May 1.

Reference Type BACKGROUND
PMID: 17472995 (View on PubMed)

Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG, Carter WO, Hellio Le Graverand MP, Kloppenburg M. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology. 2006 Jun;239(3):811-7. doi: 10.1148/radiol.2393050253.

Reference Type BACKGROUND
PMID: 16714463 (View on PubMed)

Hayes CW, Jamadar DA, Welch GW, Jannausch ML, Lachance LL, Capul DC, Sowers MR. Osteoarthritis of the knee: comparison of MR imaging findings with radiographic severity measurements and pain in middle-aged women. Radiology. 2005 Dec;237(3):998-1007. doi: 10.1148/radiol.2373041989. Epub 2005 Oct 26.

Reference Type BACKGROUND
PMID: 16251398 (View on PubMed)

Simkin PA. Bone pain and pressure in osteoarthritic joints. Novartis Found Symp. 2004;260:179-86; discussion 186-90, 277-9.

Reference Type BACKGROUND
PMID: 15283450 (View on PubMed)

Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, Keyser CP, Clohisy DR, Adams DJ, O'Leary P, Mantyh PW. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience. 2002;113(1):155-66. doi: 10.1016/s0306-4522(02)00165-3.

Reference Type BACKGROUND
PMID: 12123694 (View on PubMed)

Hukkanen M, Konttinen YT, Rees RG, Gibson SJ, Santavirta S, Polak JM. Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers. J Rheumatol. 1992 Aug;19(8):1252-9.

Reference Type BACKGROUND
PMID: 1383542 (View on PubMed)

Hunter DJ, Gerstenfeld L, Bishop G, Davis AD, Mason ZD, Einhorn TA, Maciewicz RA, Newham P, Foster M, Jackson S, Morgan EF. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res Ther. 2009;11(1):R11. doi: 10.1186/ar2601. Epub 2009 Jan 26.

Reference Type BACKGROUND
PMID: 19171047 (View on PubMed)

Related Links

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http://www.nebh.org

New England Baptist Hospital Website

Other Identifiers

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NEBH 2008-018

Identifier Type: -

Identifier Source: org_study_id