Bone properties in osteogenesis imperfecta: what can we learn from a bone biopsy beyond histology?

Mähr, Matthias; Blouin, Stéphane; Misof, Barbara M.; Paschalis, Eleftherios P.; Hartmann, Markus; Zwerina, Jochen; Fratzl‐Zelman, Nadja

doi:10.1007/s10354-021-00818-w

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Furthermore, compositional characterization, both DBM and organic composition, plays an essential role in assessing the mechanical properties of bone tissue and can provide more fundamental information that yields mechanistic insights into affecting bone quality [ 68 , 69 , 71 ]. Especially for bone collagen, there is a significant association with clinically relevant bone diseases, such as osteoporosis, osteogenesis imperfecta, and diabetes-related diseases [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

“…In diabetic bone tissue, BMD may be normal, but bone strength has decreased, which correlates with the increased formation of AGEs [ 77 , 81 ]. For osteogenesis imperfecta, it is also a disease closely associated with collagen, and studies have shown that the orientation of collagen is highly disordered and that the collagen-mineral particle network is profoundly altered [ 78 ]. Therefore, the alteration of bone quality and biomechanical performances is the macroscopic result of a sequence of composition and microstructural events.…”

Section: Discussionmentioning

confidence: 99%

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Methods for bone quality assessment in human bone tissue: a systematic review

et al. 2022

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Background For biomechanical investigations on bone or bone implants, bone quality represents an important potential bias. Several techniques for assessing bone quality have been described in the literature. This study aims to systematically summarize the methods currently available for assessing bone quality in human bone tissue, and to discuss the advantages and limitations of these techniques. Methods A systematic review of the literature was carried out by searching the PubMed and Web of Science databases from January 2000 to April 2021. References will be screened and evaluated for eligibility by two independent reviewers as per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies must apply to bone quality assessment with imaging techniques, mechanical testing modalities, and compositional characterization. The terms used for the systematic search were: “(bone quality”. Ti,ab.) AND “(human bone specimens)”. Results The systematic review identified 502 relevant articles in total. Sixty-eight articles met the inclusion criteria. Among them, forty-seven articles investigated several imaging modalities, including radiography, dual-energy X-ray absorptiometry (DEXA), CT-based techniques, and MRI-based methods. Nineteen articles dealt with mechanical testing approaches, including traditional testing modalities and novel indentation techniques. Nine articles reported the correlation between bone quality and compositional characterization, such as degree of bone mineralization (DBM) and organic composition. A total of 2898 human cadaveric bone specimens were included. Conclusions Advanced techniques are playing an increasingly important role due to their multiple advantages, focusing on the assessment of bone morphology and microarchitecture. Non-invasive imaging modalities and mechanical testing techniques, as well as the assessment of bone composition, need to complement each other to provide comprehensive and ideal information on the bone quality of human bone specimens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Methods for bone quality assessment in human bone tissue: a systematic review

et al. 2022

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“…Together with electron microscopy observations it allows us to conclude that GAGs play a more prominent role than generally assumed in the matrix-mineral interactions which determine how fast, were, and in which form the mineral is deposited, and thereby importantly contribute to the mechanical properties of bone. Moreover, this cell free mineralization approach also holds promise for the mechanic studies of mineralization related diseases where the affected matrix also in thought to trigger pathological calcification, such as the rare brittle bone disease osteogenesis imperfecta [45] , and heart valve calcification. [46] Experimental Section/Methods…”

Section: Discussionmentioning

confidence: 99%

“…In this light it will be interesting to explore the value of this model for the investigation of factors that influence the mechanical properties of bone and other mineralized tissues. Indeed, this cell free mineralization approach also holds promise for both mechanistic studies of mineralization related diseases where the mechanically affected matrix also is thought to trigger pathological calcification, such as the rare brittle bone disease osteogenesis imperfecta [46] , and heart valve calcification. [47] Experimental Section/Methods…”

Section: Discussionmentioning

confidence: 99%

A 3D cell-free bone model shows collagen mineralization is driven and controlled by the matrix

Meijden

Daviran

Rutten

et al. 2022

Preprint

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Osteons, the main organizational components of human compact bone, are cylindrical structures composed of layers of mineralized collagen fibrils, called lamellae. These lamellae have different orientations, different degrees of organization and different degrees of mineralization where the intrafibrillar and extrafibrillar mineral is intergrown into one continuous network of oriented crystals. While cellular activity is clearly the source of the organic matrix, recent in vitro studies call into question whether the cells are also involved in matrix mineralization, and suggest that this process could be simply driven by the physicochemical conditions in the extracellular matrix. Through the remineralization of demineralized bone matrix, we demonstrate the complete multiscale reconstruction of the 3D structure and composition of the osteon without cellular involvement. We then explore this cell-free in vitro system as a realistic, functional model for the in situ investigation of matrix-controlled mineralization processes. Using a combination of Raman and electron microscopy we show that glycosaminoglycans play a more prominent role than generally assumed in the matrix-mineral interactions, which determine how fast, were, and in which form the mineral is deposited. Our experiments also show that the organization of the collagen is in part a result of its interaction with the developing mineral.

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“…They are looser, allowing more water and minerals between and within them, causing hypermineralization and increased brittleness ( Fratzl-Zelman et al, 2014 ; Roschger et al, 2008 ). Furthermore, the thinner mineral plates in OI bone are sometimes less well homogeneously aligned and have an altered phosphate-to-carbonate ratio ( Bart et al, 2014 ; Fratzl et al, 1996 ; Mähr et al, 2021 ). The misalignment of mineral plates in OI bone is also reflected in the decreased bone density, as determined by dual-energy X-ray absorptiometry (DXA), of individuals with OI – whose bone is, in fact, hypermineralized.…”

Section: Extracellular or Intracellular Environment: Which Has A Larg...mentioning

confidence: 99%

Dissecting the phenotypic variability of osteogenesis imperfecta

Garibaldi

Besio

Dalgleish

et al. 2022

Disease Models &Amp; Mechanisms

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Osteogenesis imperfecta (OI) is a heterogeneous family of collagen type I-related diseases characterized by bone fragility. OI is most commonly caused by single-nucleotide substitutions that replace glycine residues or exon splicing defects in the COL1A1 and COL1A2 genes that encode the α1(I) and α2(I) collagen chains. Mutant collagen is partially retained intracellularly, impairing cell homeostasis. Upon secretion, it assembles in disorganized fibrils, altering mineralization. OI is characterized by a wide range of clinical outcomes, even in the presence of identical sequence variants. Given the heterotrimeric nature of collagen I, its amino acid composition and the peculiarity of its folding, several causes may underlie the phenotypic variability of OI. A deep analysis of entries regarding glycine and splice site collagen substitution of the largest publicly available patient database reveals a higher risk of lethal phenotype for carriers of variants in α1(I) than in α2(I) chain. However, splice site variants are predominantly associated with lethal phenotype when they occur in COL1A2. In addition, lethality is increased when mutations occur in regions of importance for extracellular matrix interactions. Both extracellular and intracellular determinants of OI clinical severity are discussed in light of the findings from in vitro and in vivo OI models. Combined with meticulous tracking of clinical cases via a publicly available database, the available OI animal models have proven to be a unique tool to shed light on new modulators of phenotype determination for this rare heterogeneous disease.

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Bone properties in osteogenesis imperfecta: what can we learn from a bone biopsy beyond histology?

Cited by 7 publications

References 32 publications

Methods for bone quality assessment in human bone tissue: a systematic review

Methods for bone quality assessment in human bone tissue: a systematic review

A 3D cell-free bone model shows collagen mineralization is driven and controlled by the matrix

Dissecting the phenotypic variability of osteogenesis imperfecta

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