Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture

TY - JOUR

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 -