Histopathology of osteogenesis imperfecta bone. Supramolecular assessment of cells and matrices in the context of woven and lamellar bone formation using light, polarization and ultrastructural microscopy

Shapiro, Frederic; Maguire, Kathleen; Swami, Srilatha; Zhu, Hui; Flynn, Evelyn; Wang, Jamie; Wu, Joy Y.

doi:10.1016/j.bonr.2020.100734

Cited by 13 publications

(18 citation statements)

References 124 publications

(107 reference statements)

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“…To further characterise the potential capacity for mechanotransduction, we determined the osteocyte density (N.Ot/B.Ar) of NB and EB within the hollow dome-shaped space under the CaP. For this purpose, PLM enables unequivocal discrimination between woven bone (WB) areas and lamellar bone (LB) areas [ 42 , 43 ]. Additionally, exploiting the autoluminescence from the embedding resin, correlative brightfield and epifluorescence microscopy allows distinguishing between resin-filled osteocyte lacunae and areas of ongoing mineralisation.…”

Section: Resultsmentioning

confidence: 99%

Bone without borders – Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope

Shah

Jolic

Micheletti

et al. 2023

Bioactive Materials

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Section: Resultsmentioning

confidence: 99%

Bone without borders – Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope

Shah

Jolic

Micheletti

et al. 2023

Bioactive Materials

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“…They indicated: “polarized light microscopy…showed that the interlamellar distance in both OI cases was half the normal value”. Our recent study on the histopathology of OI bone demonstrated lamellar bone in both the relatively severe progressively deforming variants as well as the benign autosomal dominant variants (Shapiro et al, 2021). We also documented the more cellular nature of both woven and lamellar OI bone compared to normal human bone; this in effect reflecting the diminished matrix synthesis in OI even though the cell components are actively attempting synthesis.…”

Section: Discussionmentioning

confidence: 97%

“…Knowledge of the histopathology of lamellar bone in OI is crucial to an ability to appropriately quantify the lamellae by PLM. The flattened elliptical shape of mature osteocytes in normal lamellar bone has been well defined, as has the fact that osteocytes in OI bone tend to a more oval shape in both animal (oim mouse model) (Carriero et al, 2014) and human (Shapiro et al, 2021) forms. The orientation of the canaliculi also clearly aids in defining the orientation of the lamellae, since canaliculi passing at right angles from the side walls of the oval/elliptical osteocyte and at right angles to the lamellae are good indicators that the lamellae have been sectioned without obliquity along their longitudinal or transverse axes (Shapiro, 1988; Kerschnitzki et al, 2011; Shapiro and Wu, 2019).…”

Section: Discussionmentioning

confidence: 99%

LAMELLAR THICKNESS MEASUREMENTS IN NORMAL AND OSTEOGENESIS IMPERFECTA HUMAN BONE, with development of a method of automated thickness averaging to simplify quantitation

Chow

Ryan

Shefelbine

et al. 2022

Preprint

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Purpose: Lamellar bone that forms in moderate and severe osteogenesis imperfecta (OI) is often composed of structurally irregular lamellae compared to those in normal bone. Polarization light microscopy (PLM) demonstrates lamellar bone well but has rarely been used for quantitative studies; information available on normal bone lamellae tends to be variable and studies specifically assessing OI bone lamellae have not been done. We report on PLM histomorphometry quantifying bright and dark lamellar thicknesses in normal and OI bone. Manual measurements of individual lamellar thicknesses have been made on histologic sections using the cellSens image analysis system; in an effort to augment the number of measurements we also developed a method of automated thickness averaging in quantifying regions of lamellae. Methods: Femoral and tibial cortical bone fragments from 5 individuals 5 to 26 years old (without molecular bone disorders) and 8 individuals 5 to 16 years old with progressively deforming Sillence III OI were obtained. The fragments were decalcified, infiltrated in JB4 solution, embedded in JB4 plastic, sectioned at 5 micron thickness and stained with 1% toluidine blue for light and polarizing microscopy. Manual measurements: Strict criteria for measurement, primarily to eliminate oblique lamellae, included accumulations of 16-20 bright and dark lamellae under PLM with a relatively narrow range of thicknesses, flattened elliptical osteocytes along the longitudinal axis of the lamellae and canaliculi passing from the walls of the osteocyte lacunae at right angles to the lamellae. Histomorphometric measurements of bright and dark lamellae by PLM were made at 20X magnification. Automated measurements: A script for automated measurement of average lamellar thicknesses from PLM images was developed in MATLAB (Mathworks, Natick, MA) to make measurement faster and less subjective. The script isolates a region from an image for measurement and marks each pixel as either bright or dark based on a local average intensity threshold. It then takes multiple pixel measurements along the length of the lamellae in the image and returns the average thickness of each in microns. Results: 1. OI bone mean lamellar thickness values are always less than those in normal bone. The mean value for all OI bright and dark lamellae combined is 1.80 +/- 0.72 microns and the value in normal bone is 2.54 +/- 0.92 microns. 2. Mean value for the bright lamellae is less than that for the dark lamellae in both normal and OI bone. The mean value for bright lamellae in OI is 1.47 +/- 0.53 microns and for dark lamellae 2.18 +/- 0.72 microns; in normal bone the mean value for bright lamellae is 2.06 +/- 0.54 microns and for dark lamellae 3.07 +/- 0.96 microns. The differences are statistically significant: between groups of normal and OI lamellae (p<0.001), normal and OI light bands (p<0.001), and normal and OI dark bands (p<0.001). 3. Ratio of mean values for bright/dark lamellar thicknesses is the same in OI and normal bone. The ratio in OI bone is 0.67 (range: 0.54 to 0.83) and in normal bone 0.67 (range: 0.60 to 0.88). 4. Validation of automated vs. manual datasets: For each lamella in the validation dataset, the percent difference between the automated and manual measurements was calculated. The mean of the absolute values of these percent differences was 18.9%, a statistically non-significant difference (p = 0.0518). Discussion and conclusions: Lamellar bone that forms in moderate and severe OI is composed of thinner and less regular lamellae than those in normal bone. 1. PLM histomorphometry shows mean lamellar thicknesses (bright and dark merged) are statistically significantly decreased in OI compared to normal bone as are bright and dark lamellar thicknesses measured independently. 2. The automated method can be adapted readily to the assessment process for lamellar thicknesses and is, most likely, more accurate since it averages a greatly increased number of measurements per individual lamella. 3. Lamellar thickness measurements can be helpful in assessing the effect of specific collagen mutations on OI bone synthesis and warrant inclusion in both research and clinical histomorphometric assessments.

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“…Another pathology where static and dynamic osteogenesis explains some evidence is osteogenesis imperfecta (OI), as described by Shapiro et al in 2020 [39]. The terms "static" and "dynamic" osteogenesis correspond to the definitions previously reported by Shapiro [40], i.e., with regard to the differences in osteoblast location/function in "mesenchymal osteoblasts" (MOBLs) that produce woven bone and "surface osteoblasts" (SOBLs) that produce lamellar bone.…”

Section: Experimental Evidence For So and Do Occurrencementioning

confidence: 94%

“…After the production of woven bone by MOBLs, SOBLs continued to secrete lamellar bone close to the woven scaffold. Shapiro and coworkers [39] observed in OI that "the more severe the variant of OI is, the greater the persistence of woven bone and the more immature the structural pattern; the pattern shifts to a structurally stronger lamellar arrangement once a threshold accumulation for an adequate scaffold of woven bone has been reached". The authors correlated SO and DO with the subsequent temporal phases of woven (first) and lamellar (later) bone deposition by MOBLs and SOBLs, respectively, in the production of normal/healed/pathological bone.…”

Section: Experimental Evidence For So and Do Occurrencementioning

confidence: 99%

Static Osteogenesis versus Dynamic Osteogenesis: A Comparison between Two Different Types of Bone Formation

Ferretti

Palumbo

2021

Applied Sciences

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In contrary to what has traditionally been believed, bone formation can occur through two different types of osteogenesis: static (SO) and dynamic (DO) osteogenesis, which are thus named because the former is characterized by pluristratified cords of unexpectedly stationary osteoblasts which differentiate at a fairly constant distance from the blood capillaries and transform into osteocytes without moving from the onset site, while the latter is distinguished by the well-known typical monostratified laminae of movable osteoblasts. The two types of osteogenesis differ in multiple aspects from both structural and functional viewpoints. Besides osteoblast arrangement, polarization, and motion, SO and DO differ in terms of time of occurrence (first SO and later DO), conditioning factors to which they are sensitive (endothelial-derived cytokines or mechanical loading, respectively), distribution of osteocytes to which they give rise (haphazard or ordered in planes, respectively), the collagen texture resulting from the different deposition types (woven or lamellar, respectively), the mechanical properties of the bone they form (poor for SO due to the high cellularity and woven texture and good for DO since osteocytes are located in more suitable conditions to perceive loading), and finally the functions of each, i.e., SO provides a preliminary rigid scaffold on which DO can take place, while DO produces bone tissue according to mechanical/metabolic needs..

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Histopathology of osteogenesis imperfecta bone. Supramolecular assessment of cells and matrices in the context of woven and lamellar bone formation using light, polarization and ultrastructural microscopy

Cited by 13 publications

References 124 publications

Bone without borders – Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope

Bone without borders – Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope

LAMELLAR THICKNESS MEASUREMENTS IN NORMAL AND OSTEOGENESIS IMPERFECTA HUMAN BONE, with development of a method of automated thickness averaging to simplify quantitation

Static Osteogenesis versus Dynamic Osteogenesis: A Comparison between Two Different Types of Bone Formation

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