Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture
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Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. / Busse, Björn; Bale, Hrishikesh A; Zimmermann, Elizabeth A; Panganiban, Brian; Barth, Holly D; Carriero, Alessandra; Vettorazzi, Eik; Zustin, Josef; Hahn, Michael; Ager, Joel W; Püschel, Klaus; Amling, Michael; Ritchie, Robert O.
in: SCI TRANSL MED, Jahrgang 5, Nr. 193, 10.07.2013, S. 193ra88.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture
AU - Busse, Björn
AU - Bale, Hrishikesh A
AU - Zimmermann, Elizabeth A
AU - Panganiban, Brian
AU - Barth, Holly D
AU - Carriero, Alessandra
AU - Vettorazzi, Eik
AU - Zustin, Josef
AU - Hahn, Michael
AU - Ager, Joel W
AU - Püschel, Klaus
AU - Amling, Michael
AU - Ritchie, Robert O
PY - 2013/7/10
Y1 - 2013/7/10
N2 - 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.
AB - 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.
KW - Aging
KW - Biomechanical Phenomena
KW - Bone Density
KW - Bone and Bones
KW - Collagen
KW - Disease Susceptibility
KW - Female
KW - Fractures, Bone
KW - Humans
KW - Male
KW - Risk Factors
KW - Spectrum Analysis
KW - Synchrotrons
KW - Vitamin D Deficiency
KW - X-Ray Microtomography
U2 - 10.1126/scitranslmed.3006286
DO - 10.1126/scitranslmed.3006286
M3 - SCORING: Journal article
C2 - 23843449
VL - 5
SP - 193ra88
JO - SCI TRANSL MED
JF - SCI TRANSL MED
SN - 1946-6234
IS - 193
ER -