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A novel algorithm for a precise analysis of subchondral bone alterations.

ABSTRACT: Subchondral bone alterations are emerging as considerable clinical problems associated with articular cartilage repair. Their analysis exposes a pattern of variable changes, including intra-lesional osteophytes, residual microfracture holes, peri-hole bone resorption, and subchondral bone cysts. A precise distinction between them is becoming increasingly important. Here, we present a tailored algorithm based on continuous data to analyse subchondral bone changes using micro-CT images, allowing for a clear definition of each entity. We evaluated this algorithm using data sets originating from two large animal models of osteochondral repair. Intra-lesional osteophytes were detected in 3 of 10 defects in the minipig and in 4 of 5 defects in the sheep model. Peri-hole bone resorption was found in 22 of 30 microfracture holes in the minipig and in 17 of 30 microfracture holes in the sheep model. Subchondral bone cysts appeared in 1 microfracture hole in the minipig and in 5 microfracture holes in the sheep model (n?=?30 holes each). Calculation of inter-rater agreement (90% agreement) and Cohen's kappa (kappa?=?0.874) revealed that the novel algorithm is highly reliable, reproducible, and valid. Comparison analysis with the best existing semi-quantitative evaluation method was also performed, supporting the enhanced precision of this algorithm.

SUBMITTER: Gao L

PROVIDER: S-EPMC5011758 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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A novel algorithm for a precise analysis of subchondral bone alterations.

Gao Liang L Orth Patrick P Goebel Lars K H LK Cucchiarini Magali M Madry Henning H

Scientific reports 20160906

Subchondral bone alterations are emerging as considerable clinical problems associated with articular cartilage repair. Their analysis exposes a pattern of variable changes, including intra-lesional osteophytes, residual microfracture holes, peri-hole bone resorption, and subchondral bone cysts. A precise distinction between them is becoming increasingly important. Here, we present a tailored algorithm based on continuous data to analyse subchondral bone changes using micro-CT images, allowing f ...[more]

PMID: 27596562

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Project description:BackgroundSubchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.MethodsThe preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.ResultsAt both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.ConclusionCyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Project description:Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl expression, in which JNK and/or Ca(2+)/NFAT pathways were involved and therefore were engaged in enhancing the migration and differentiation of osteoclast precursors, leading to increased osteoclast activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated rats.

Dataset Information

A novel algorithm for a precise analysis of subchondral bone alterations.

Publications

A novel algorithm for a precise analysis of subchondral bone alterations.

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