Characterizing Bone Turnover in Osteoarthritic Bone Marrow Lesions in Human Knees Using Tetracycline Histology

Bone marrow lesions (BMLs) are a hallmark sign of osteoarthritis (OA) associated with clinical symptoms of pain and pain progression. Based on previous literature, BMLs are likely centers of increased bone remodeling. Currently, there is no consensus as to what defines a BML outside of its appearance on MRI. This study aimed to better understand bone remodeling rates in BML tissue versus matched OA control tissue from total knee arthroplasty (TKA) tibial plateau explants in five individuals with end stage OA. Participants were scanned with magnetic resonance imaging (MRI) six months prior to TKA. Tetracycline hydrochloride was administered to produce fluorescent double labels signifying newly mineralized bone. BMLs and paired control (BML-free) regions were identified in the tibial plateaus on the in vivo MRI images before polymethyl methacrylate embedding and sectioning. BIOQUANTOsteo and paired T tests were used to measure differences in mineral appositional rate (MAR), bone formation rate (BFR/BS), and mineralizing surface (MS/BS) on histological sections. Five tibial plateau explants showed that MAR was significantly higher in the BML group (1.14 +/- 0.3μm/day) than the control group (0.37 +/- 0.24μm/day, p = 0.0003). BFR/BS (p = 0.058) and MS/BS (p = 0.140) appeared to trend higher in the BML group (0.08 +/- 0.07μm/day, 0.064 +/- 0.046%, respectively) than in the paired control group (0.02 +/- 0.02μm/day, 0.042 +/- 0.039%, respectively). Taken together these results signify that BMLs likely have an increased rate of bone remodeling when compared to paired non BML OA tissue. This research could assist in elucidating novel therapeutic targets for treatment of knee OA and identify those needing TKA, thus improving the quality of life for affected individuals.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Engineering – Biomedical

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2025

Author dc:creator

• Rachel, Klassen

Advisors dc:contributor.advisor

• Boyd, Steven
• Manske, Sarah

Committee members dc:contributor.committeemember

• Bertram, John
• Krawetz, Roman
• Turcotte, Cassandra

• Histology
• Bone Marrow Lesion
• Osteoarthritis
• Human
• Bone Remodeling
• Bone Turnover

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

en

DOI

https://dx.doi.org/10.11575/PRISM/48960

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/121370