Diversity in intracortical remodeling in the human femoral bone: A novel view point with the morphological analysis of secondary osteons

Maeda, Junichiro; Sawamoto, Kazunobu; Kondo, Hisayoshi; Hiroaki, Matsuo; Imamura, Takeshi; Ogami-Takamura, Keiko; Okamoto, Keishi; Tomita, Masato; Osaki, Makoto; Tsurumoto, Toshiyuki

doi:10.1016/j.jos.2018.07.021

Cited by 4 publications

(7 citation statements)

References 25 publications

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“…A polished specimen of a femoral diaphysis transverse section was prepared according to the method of Maeda et al (2018). Digital images of the prepared samples were acquired using a circular polarizing microscope (Olympus BX 43, Zeiss Axio Cam Erc 5S).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of cortical bone density using clinical computed tomography images: Detection of cortical porosity areas or transitional zones in human femoral diaphyses

et al. 2023

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Age‐related changes in human trabecular bone and cortical bone are known to vary. Although the porosity of cortical bone has been suggested to increase the risk of bone fracture, most of the currently available instruments for osteoporosis testing target trabecular bone. In this study, we evaluated cortical bone density using clinical computed tomography (CT) and compared the reliability of the cortical bone density index (CDI) with that of a polished male femoral bone from the same region. CDI images revealed that the porous area of cortical bone was extended in low CDI values. Moreover, this method was used to semi‐quantitatively evaluate the cortical bones of the diaphysis of male femur specimens (n = 46). We found that there was a significant relationship (r = 0.70, p < 0.01) between the value of the cortical index (the ratio of cortical bone area to the cross‐sectional area of the femoral diaphysis) and the average of CDI in the low signal area. Our findings suggest that the smaller the cortical bone occupancy, the more areas of consequential bone density loss were present. This may be the first step toward using clinical CT to assess cortical bone density.

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Section: Methodsmentioning

confidence: 99%

Evaluation of cortical bone density using clinical computed tomography images: Detection of cortical porosity areas or transitional zones in human femoral diaphyses

et al. 2023

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Section: Introductionmentioning

confidence: 99%

“…Remodeling of cortical bone occurs through complex multicellular units containing ostb and osteoclasts, which modulate each other's function and are often responsive to some of the same growth factors and cytokines, although sometimes with different responses. (2,16) Osteocytes (terminally differentiated ostb), which constitute most of the cells in cortical bone, coordinate the differentiation and activity of ostb and osteoclasts in response to mechanical load or injury. (17) Because of the centrality of ostb to normal bone homeostasis and the availability of epigenomic and transcriptomic profiles for comparing human cell cultures of ostb, chond, MSC, and heterologous primary cell cultures, we focused on examining the epigenetics of BMD GWAS-derived SNPs in ostb and, secondarily, in chond and MSCs.…”

Section: Introductionmentioning

confidence: 99%

Prioritization of Osteoporosis‐Associated Genome‐wide Association Study (GWAS) Single‐Nucleotide Polymorphisms (SNPs) Using Epigenomics and Transcriptomics

et al. 2021

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Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome‐wide association studies (GWASs). A major challenge is to prioritize transcription‐regulatory GWAS‐derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics‐based and transcription‐based approach to identify some of the credible regulatory single‐nucleotide polymorphisms (SNPs) relevant to osteoporosis from 38 reported bone mineral density (BMD) GWASs. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 12 heterologous cell culture types. We also required that these SNPs overlap open chromatin (Deoxyribonuclease I [DNaseI]‐hypersensitive sites) and DNA sequences predicted to bind to osteoblast‐relevant transcription factors in an allele‐specific manner. From >50,000 GWAS‐derived SNPs, we identified 14 novel and credible regulatory SNPs (Tier‐1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of these genes are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical for bone formation and repair. The transcription factors predicted to bind to the Tier‐1 SNP‐containing DNA sequences also have bone‐related functions. We present evidence that some of the Tier‐1 SNPs exert their effects on BMD risk indirectly through little‐studied long noncoding RNA (lncRNA) genes, which may, in turn, control the nearby bone‐related protein‐encoding gene. Our study illustrates a method to identify novel BMD‐related causal regulatory SNPs for future study and to prioritize candidate regulatory GWAS‐derived SNPs, in general. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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“…Alternatively, in the mechanostat theory proposed by Frost (2003), bone resorption and remodeling are caused by an increase/decrease in strain above a physiologically determined strain threshold or "set point", rather than continually changing with the strain (Frost, 1997; Frost, 2003). Indeed, at the microscopic level, such a biological response is observed in the cortices of the long bones that are compatible with the mechanical environment (Maeda et al, 2018; Matsuo et al, 2019; Skedros, 1995; Skedros et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Morphological divergence in the curvature of human femoral diaphyses: Tracing the central mass distributions of cross‐sections

et al. 2021

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The diaphysis of the human femoral bone has a physiological anterior curvature; additionally, there is a curvature to the medial side or lateral side. In addition to compression stress from gravity during standing, walking, and running, these bones are continuously exposed to complex stresses from the traction forces of the various strong muscles attached to them. The femoral diaphysis is subjected to these mechanical stresses, and the direction and size of its curvature are defined according to Wolff's law and the mechanostat theory of Frost. The purpose of this study was to quantitatively evaluate the curvature of the femoral diaphysis in Japanese skeletons by determining the curve connecting the central mass distributions (CMD) of cross‐sectional images. A total of 90 right femora (46 males and 44 females) were randomly selected from modern Japanese skeletal specimens. Full‐length images of these bones were acquired using a clinical computed tomography scanner. The range between the lower end of the lesser trochanter and the adductor tubercle of each femur was divided at regular intervals to obtain ten planes, and nine levels were analyzed. The CMD curve was determined by connecting the CMDs of each of the nine cross‐sections. First, the CMD of a cross‐section in each of the nine slices was calculated, and the nine trajectories were superimposed from above. Then, by converting the shape of the entire CMD curve to superimpose the coordinates of the endpoint on the starting point, a closed arc representing the curvature of the femur was determined. For both males and females, the patterns varied from mostly medial to largely lateral curvature. The size of the curvature also varied for individuals. By analyzing only the coordinates of the vertex of the CMD curve of each femoral bone, the outlines of the diaphyseal curvatures could be recognized. The femora were thereby divided into two groups: medial bending and lateral bending. Considering males and females together, the number in the lateral‐curvature group (n = 51) was larger than that in the medial‐curvature group (n = 39). Moreover, the average age of the lateral‐curvature group was significantly higher than that of the medial‐curvature group (p < 0.05). In males, with an increase in the cortical bone proportion of the cross‐sectional area, the anterior vertex of diaphyseal bending tended to be more prominent. This cortical proportion was significantly higher in the medial‐curvature groups than in the lateral‐curvature group (p < 0.01). The phenomena observed in this study may be related to pathophysiologies such as atypical fractures of the femur and osteoarthritis of the knee joints.

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Diversity in intracortical remodeling in the human femoral bone: A novel view point with the morphological analysis of secondary osteons

Cited by 4 publications

References 25 publications

Evaluation of cortical bone density using clinical computed tomography images: Detection of cortical porosity areas or transitional zones in human femoral diaphyses

Evaluation of cortical bone density using clinical computed tomography images: Detection of cortical porosity areas or transitional zones in human femoral diaphyses

Prioritization of Osteoporosis‐Associated Genome‐wide Association Study (GWAS) Single‐Nucleotide Polymorphisms (SNPs) Using Epigenomics and Transcriptomics

Morphological divergence in the curvature of human femoral diaphyses: Tracing the central mass distributions of cross‐sections

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