Modalities for Visualization of Cortical Bone Remodeling: The Past, Present, and Future

Abstract

Bone's ability to respond to load-related phenomena and repair microdamage is achieved through the remodeling process, which renews bone by activating groups of cells known as basic multicellular units (BMUs). The products of BMUs, secondary osteons, have been extensively studied via classic two-dimensional techniques, which have provided a wealth of information on how histomorphology relates to skeletal structure and function. Remodeling is critical in maintaining healthy bone tissue; however, in osteoporotic bone, imbalanced resorption results in increased bone fragility and fracture. With increasing life expectancy, such degenerative bone diseases are a growing concern. The three-dimensional (3D) morphology of BMUs and their correlation to function, however, are not well-characterized and little is known about the specific mechanisms that initiate and regulate their activity within cortical bone. We believe a key limitation has been the lack of 3D information about BMU morphology and activity. Thus, this paper reviews methodologies for 3D investigation of cortical bone remodeling and, specifically, structures associated with BMU activity (resorption spaces) and the structures they create (secondary osteons), spanning from histology to modern ex vivo imaging modalities, culminating with the growing potential of in vivo imaging. This collection of papers focuses on the theme of "putting the 'why' back into bone architecture." Remodeling is one of two mechanisms "how" bone structure is dynamically modified and thus an improved 3D understanding of this fundamental process is crucial to ultimately understanding the "why."

Keywords: basic multicellular unit; bone; micro-CT; remodeling; synchrotron.

Figure 1

Illustration of a BMU showing the classic ‘cutting’ and ‘closing’ cone morphology. Osteoclasts located in the BMU’s cutting cone are attracted to areas of damaged bone indicated by the microcrack [based on Ref. (26)], as well as change in the canalicular network (black lacunae indicative of osteocyte apoptosis) caused by mechanical stimuli such as cyclic loading (based on Ref. (24)).

Figure 2

Left: reconstructed micro-CT image of landmarked BMUs in a black bear metacarpal; right: 3D render of bone diaphysis superimposed over BMUs. Diaphysis length = 31.84 mm.

Figure 3

3D reconstruction of a human femur section depicting BMUs and osteocyte lacunae acquired by SR micro-CT at a 1.47 µm resolution (58). Image provided by Dr. Yasmin Carter.

Figure 4

(A) Schematic of attenuation based X-ray imaging where images are produced based on the degree of absorption relative to an object’s internal structure. (B) Schematic of in-line phase-contrast imaging based on an object’s refractive properties. As X-rays target an object at different angles, variations in the object’s internal structure will refract the X-rays and cause a shift in the light wave as it propagates through and increasing the object-to-detector distance will produce a contrast image (76). Reprint permission granted by the publisher.

Figure 5

Reconstructed slices of rat forelimbs depicting visualization of cortical porosity based on the imaging system used: (A) in vivo laboratory SkyScan 1176 micro-CT (18 μm, 1.2–1.5 Gy dose), (B) in vivo synchrotron micro-CT slice measured using the C4742-56-12HR camera (11.8 μm, 2.53 Gy dose), (C) in vivo laboratory SkyScan 1176 (9 μm, 11.7–18.2 Gy dose) (78). Reprint permission granted by the publisher.

Figure 6

Images showing in vivo matched scans of a rat forelimb acquired with SR micro-CT (11.8 μm, 2.53 Gy). Scan (B) was carried out two weeks after scan (A) on the same rat’s forelimb. Image (C) is an enlarged section of image (B) (red rectangle) displaying new remodeling events (red arrows).