Sci Transl Med 10 July 2013: Vol. 5, Issue 193, p. 193ra88
Björn Busse 1,2, b.busse at uke.uni-hamburg.de
Hrishikesh A. Bale 2,
Elizabeth A. Zimmermann 1,2,3,
Brian Panganiban 2,
Holly D. Barth 2,3,
Alessandra Carriero 2,
Eik Vettorazzi 4,
Josef Zustin 5,
Michael Hahn 1,
Joel W. Ager III 2,
Klaus Püschel 6,
Michael Amling 1 and
Robert O. Ritchie 2,3
1Department of Osteology and Biomechanics, University Medical Center Hamburg, D-22529 Hamburg, Germany.
2Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
3Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, USA.
4Department of Medical Biometry and Epidemiology, University Medical Center Hamburg, D-20246 Hamburg, Germany.
5Institute of Pathology, University Medical Center Hamburg, D-20246 Hamburg, Germany.
6Department of Forensic Medicine, University Medical Center Hamburg, D-20246 Hamburg, Germany.
Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Fracture susceptibility in the context of low vitamin D has been primarily associated with defective mineralization of collagenous matrix (osteoid). However, bone’s fracture resistance is due to toughening mechanisms at various hierarchical levels ranging from the nano- to the microstructure. Thus, we hypothesize that the increase in fracture risk with vitamin D deficiency may be triggered by numerous pathological changes and may not solely derive from the absence of mineralized bone. We found that the characteristic increase in osteoid-covered surfaces in vitamin D–deficient bone hampers remodeling of the remaining mineralized bone tissue. Using spatially resolved synchrotron bone mineral density distribution analyses and spectroscopic techniques, we observed that the bone tissue within the osteoid frame has a higher mineral content with mature collagen and mineral constituents, which are characteristic of aged tissue. In situ fracture mechanics measurements and synchrotron radiation micro–computed tomography of the crack path indicated that vitamin D deficiency increases both the initiation and propagation of cracks by 22 to 31%. Thus, vitamin D deficiency is not simply associated with diminished bone mass. Our analyses reveal the aged nature of the remaining mineralized bone and its greatly decreased fracture resistance. Through a combination of characterization techniques spanning multiple size scales, our study expands the current clinical understanding of the pathophysiology of vitamin D deficiency and helps explain why well-balanced vitamin D levels are essential to maintain bone’s structural integrity.
Copyright © 2013, American Association for the Advancement of Science
- They used state-of-the-art technology to characterize bone quality on the smallest of size scales, around 100 micrometers, or roughly the diameter of a human hair.
- They recruited 30 subjects — half deficient and half with normal vitamin D levels — and scanned their bones with synchrotron radiation-based microcomputed tomography.
This special brand of X-ray can record nano-scale structural features of one's bones in 3-D. Its light beams can also penetrate deep within the bone to reveal details that can't been seen by a regular X-ray.
- On the surface of the bone, fewer minerals, like calcium, were observed, which paralleled prior work. In contrast, deep within the bone, mineralization was actually denser by three-fold.
Cells responsible for upkeep and remodeling the bone were unable to access these deeper layers in people with vitamin D deficiency, according to the authors.
- The researchers noticed that these islands of mineralized bone were surrounded by a collagenous boundary, which prevented them from being properly remodeled.
Cut off from a supply of osteoclasts, cells that help break down and absorb older bone tissue, these isolated sections of mineralized bone begin to age.
At the same time, overall bone mineralization decreases from a lack of calcium.
Editorial: Deconstructing Vitamin D Deficiency on the study is also behind the same paywall
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