Perspective: Ultrastructural Origins of Bone Fragility

Jitin Samuel, Rohit Khanna, Xiaodu Wang

Department of Mechanical Engineering, University of Texas at San Antonio, One UTSA Circle

DOI: https://doi.org/10.17140/orhoj-1-101 · Published 2025-09-10 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2025 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Keywords: human bones, lamella

Perspective Perspective: Ultrastructural Origins of Bone Article Fragility * *Corresponding author Xiaodu Wang, PhD * Jitin Samuel, MS; Rohit Khanna, PhD; Xiaodu Wang, PhD Professor Mechanical and Biomedical Engineering The University of Texas at San Antonio Department of Mechanical Engineering, University of Texas at San Antonio, One UTSA Circle One UTSA Circle San Antonio, TX 78249, USA San Antonio, TX 78249, USA Tel. 210-458-5565 Fax: 210-458-6504 E-mail: xiaodu.wang@utsa.edu Bone fragility fractures due to deteriorated tissue quality are a major healthcare con- cern in the healthcare of elderly who are at particularly high risk of bone fractures. Thus, iden- Volume 1 : Issue 1 tifying and treating patients at risk is critical in sustaining a healthy life style for the elderly. Article Ref. #: 1000ORHOJ1101 Currently, bone mass or Bone Mineral Density (BMD) is commonly employed by physicians as a measure to predict the risk of such fractures. However, BMD is often a poor predictor of Article History overall bone quality,1 showing that patients with healthy BMD levels may still be susceptible to th 2,3 Received: February 26 , 2016 fragility fractures. Hence, reliable prediction of bone fragility fractures requires understand- st Accepted: March 31st, 2016 ing the underlying origins of bone fragility fracture beyond the qualitative estimation provided st Published: April 1st, 2016 by BMD measurements.

Many biological materials exhibit a recurring motif of hierarchical structures, which Citation Samuel J, Khanna R, Wang X. Perspec- is optimized by nature to adapt to surrounding environments (e.g. mechanical loading). In tive: Ultrastructural origins of bone fra- general, the key attribute of the hierarchically structured materials is that their bulk behavior is gility. Osteol Rheumatol Open J. 2016; not simply a function of the mechanical properties of their primary constituents, but also of the 1(1): 1-3. doi: 10.17140/ORHOJ-1-101 shape and arrangement of these constituents at different length scales. These constituents are integrated to form basic building blocks at nanoscopic levels, which are then further arranged to form building blocks at higher length scales. Similarly, bone as the primary load bearing tis- sue in the human body also exhibits a hierarchical structure.

Among the different hierarchies of human bones, lamella is the fundamental building block, which is a sheet like structure comprising parallelly arranged mineralized collagen fibrils surrounded by an extra-fibrillar matrix (EFM) (Figure 1). Advanced microscopy techniques demonstrate that mineralized collagen fibrils consist of mineral crystals orderly arranged within 5,6 collagen fibrils.5,6 Several structural models of mineralized collagen fibrils are proposed based on the experimental observations and exhibit the efficacy to capture the key features of the 7-9 arrangement and the mechanistic behavior of its moieties.7-9 However, the less explored and understood is the EFM in bone lamella.

Copyright © 2016 Wang X. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Figure 1: Schematic of bone ultrastructure.

Differing opinions have been raised by researchers on a pivotal role in the mechanical behavior of bone tissues. Sec- the structure and arrangement of mineral crystals in and around ond, hydration is necessary for the extra-fibrillar matrix to sus- the collagen phase. Nonetheless, there exists a general consen- tain large strains, thereby imparting toughness to bone. Third, sus that “plate-like” mineral crystals exist both in the gap re- non-collagenous proteins such as proteoglycans are potentially gions of collagen fibrils to form mineralized collagen fibrils and a pivotal ultrastructural component that dictate the toughness of also outside the fibrils as part of the EFM. In fact, recent Trans- bone. In conclusion, the extra-fibrillar matrix in bone plays a mission electron microscopy (TEM) results reinforce this con- significant role in the toughness of bone.

jecture, showing that lower density regions were embedded in a higher density region at nanoscopic levels,5 thereby indicating CONFLICTS OF INTEREST: None.

that the softer collagen fibrils are surrounded by harder mineral crystals. Thus, it could be assumed that mineral crystals are a

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