Role of Bone in Knee Osteoarthritis (OA)

Osteoarthritis, Knee Clinical Trial

Official title:

The Role of Bone and Its Measurement in Knee Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00850538
• Other study ID #: NEBH 2008-018
• Status: Completed
• Phase: N/A
• First received: February 23, 2009
• Last updated: November 2, 2015
• Start date: July 2008
• Est. completion date: April 2013

Study information

• Verified date: November 2015
• Source: The New England Baptist Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

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

Procedure:
• Primary Total Knee Replacement
Fluid, bone, and meniscus specimens obtained from total joint replacement will be collected.

Locations

Country	Name	City	State
Australia	University of Sydney	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
The New England Baptist Hospital

Country where clinical trial is conducted

Australia, 

References & Publications (16)

Burr DB. The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 2004 Apr;70:77-80. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Oct 26. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 May 1. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Reinus WR, Fischer KC, Ritter JH. Painful transient tibial edema. Radiology. 1994 Jul;192(1):195-9. — View Citation

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

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Viable Specimens for Genetic Analysis		Tissue samples collected at time of surgery	No

External Links

•   New England Baptist Hospital Website