The quantification of 3D-trabecular architecture of the fourth cervical vertebra using CT osteoabsorptiometry and micro-CT.

BACKGROUND: Bone functional adaptation rationalises the inhomogeneous morphology found in bone. By means of computed tomography osteoabsorptiometry and micro-computed tomography, the mineralisation of the subchondral endplates and trabecular microstructure of vertebral bodies can be assessed to visualise the chronic loading conditions bone endures over time. In this study, we determined cancellous and compartment-specific trabecular architecture in the cervical vertebra to aid with successful integration of orthopaedic implants. METHODS: We examined the micro-computed tomography scans of seven prospectively healthy C4 vertebrae, evaluated their microstructure parameters (bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number per volume (Tb.N), connectivity density (Conn.D), structure model index (SMI), and degree of anisotropy (DA), and compared the trabecular architecture in twelve predefined volumes of interest: the cranial and caudal 0-10%, 10-15%, and 25-50% in both the ventral and dorsal half. Using computed tomography osteoabsorptiometry, the subchondral bone mineralisation of the subchondral endplates of nine C4 vertebrae was also evaluated. RESULTS: Highest mineralisation is located dorsally at the endplates. Tb.Sp and Tb.N were the only two parameters that displayed significant differences in averaged values of VOI. Nonetheless, distinct, consistent ventral-dorsal modulations were seen in matched sample ventral-dorsal comparison in the BV/TV, BS/BV, and SMI overall levels, as well as in Tb.Th in the three caudal levels. To simplify, the vertebra was split into ventral-cranial, dorsal-cranial, ventral-caudal, and dorsal-caudal equal quarters. The ventral quarters display lower BV/TV, respectively, higher BS/BV and SMI than their sample paired dorsal quarters. The ventral-cranial quarter shows the lowest BV/TV and the highest BS/BV and SMI, describing spacious cancellous bone with rod-like trabeculae. In contrast, the dorsal-caudal quarter exhibits the highest BV/TV and Tb.Th and the lowest BS/BV and SMI, illustrating thicker, denser, and more plate-like trabeculae. The dorsal-cranial and ventral-caudal quarters are comparable and represent intermediate characteristics. CONCLUSIONS: CT-OAM and µCT demonstrate the interdependence of compact and trabecular bone in response to long-term loading conditions. Results show highest mineralisation in the dorso-caudal part of the C4 vertebra. Recommended placement of orthopaedic implants should be positioned dorsally with screws anchored in the dorsal-caudal region.

Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc.

Introduction: An in vitro model that appropriately recapitulates the degenerative disc disease (DDD) microenvironment is needed to explore clinically relevant cell-based therapeutic strategies for early-stage degenerative disc disease. We developed an advanced 3D nucleus pulposus (NP) microtissues (µT) model generated with cells isolated from human degenerating NP tissue (Pfirrmann grade: 2-3), which were exposed to hypoxia, low glucose, acidity and low-grade inflammation. This model was then used to test the performance of nasal chondrocytes (NC) suspension or spheroids (NCS) after pre-conditioning with drugs known to exert anti-inflammatory or anabolic activities. Methods: NPµTs were formed by i) spheroids generated with NP cells (NPS) alone or in combination with ii) NCS or iii) NC suspension and cultured in healthy or degenerative disc disease condition. Anti-inflammatory and anabolic drugs (amiloride, celecoxib, metformin, IL-1Ra, GDF-5) were used for pre-conditioning of NC/NCS. The effects of pre-conditioning were tested in 2D, 3D, and degenerative NPµT model. Histological, biochemical, and gene expression analysis were performed to assess matrix content (glycosaminoglycans, type I and II collagen), production and release of inflammatory/catabolic factors (IL-6, IL-8, MMP-3, MMP-13) and cell viability (cleaved caspase 3). Results: The degenerative NPµT contained less glycosaminoglycans, collagens, and released higher levels of IL-8 compared to the healthy NPµT. In the degenerative NPµT, NCS performed superior compared to NC cell suspension but still showed lower viability. Among the different compounds tested, only IL-1Ra pre-conditioning inhibited the expression of inflammatory/catabolic mediators and promoted glycosaminoglycan accumulation in NC/NCS in DDD microenvironment. In degenerative NPµT model, preconditioning of NCS with IL-1Ra also provided superior anti-inflammatory/catabolic activity compared to non-preconditioned NCS. Conclusion: The degenerative NPµT model is suitable to study the responses of therapeutic cells to microenvironment mimicking early-stage degenerative disc disease. In particular, we showed that NC in spheroidal organization as compared to NC cell suspension exhibited superior regenerative performance and that IL-1Ra pre-conditioning of NCS could further improve their ability to counteract inflammation/catabolism and support new matrix production within harsh degenerative disc disease microenvironment. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of IVD repair.

Influence of size and shape of the auricular surfaces on subchondral bone density distribution in the sacroiliac joint.

The sacroiliac auricular surface has a variable morphology and size. The impact of such variations on subchondral mineralization distribution has not been investigated. Sixty-nine datasets were subjected to CT-osteoabsorptiometry for the qualitative visualization of chronic loading conditions of the subchondral bone plate using color-mapped densitograms based on Hounsfield Units in CT. Auricular surface morphologies were classified into three types based on posterior angle size: Type 1: >160°, Type 2: 130-160° and Type 3: <130°. Auricular surface size was categorized based on the mean value (15.4 cm2 ) separating the group into 'small' and 'large' joint surfaces. Subchondral bone density patterns were qualitatively classified into four color patterns: two marginal patterns (M1 and M2) and two non-marginal patterns (N1 and N2) and each iliac and sacral surface was subsequently categorized. 'Marginal' meant that 60-70% of the surface was less mineralized compared with the highly dense regions and vice versa for the 'non-marginal' patterns. M1 had anterior border mineralization and M2 had mineralization scattered around the borders. N1 had mineralization spread over the whole superior region, N2 had mineralization spread over the superior and anterior regions. Auricular surface area averaged 15.4 ± 3.6 cm2 , with a tendency for males to have larger joint surfaces. Type 2 was the most common (75%) and type 3 the least common morphology (9%). M1 was the most common pattern (62% of surfaces) by sex (males 60%, females 64%) with the anterior border as the densest region in all three morphologies. Sacra have a majority of surfaces with patterns from the marginal group (98%). Ilia have mineralization concentrated at the anterior border (patterns M1 and N2 combined: 83%). Load distribution differences related to auricular surface morphology seems to have little effect on long-term stress-related bone adaptation visualized with CT-osteoabsorptiometry. Higher iliac side mineralization was observed in larger joint surfaces and age-related morphomechanical size alterations were seen in males.