title: Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture.
abstract: 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.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg, D-22529 Hamburg, Germany. b.busse@uke.uni-hamburg.de
authors.forename: Björn
authors.initials: B
authors.lastname: Busse
authors.forename: Hrishikesh A
authors.initials: HA
authors.lastname: Bale
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Zimmermann
authors.forename: Brian
authors.initials: B
authors.lastname: Panganiban
authors.forename: Holly D
authors.initials: HD
authors.lastname: Barth
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carriero
authors.forename: Eik
authors.initials: E
authors.lastname: Vettorazzi
authors.forename: Josef
authors.initials: J
authors.lastname: Zustin
authors.forename: Michael
authors.initials: M
authors.lastname: Hahn
authors.forename: Joel W
authors.initials: JW
authors.lastname: Ager
authors.forename: Klaus
authors.initials: K
authors.lastname: Püschel
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ritchie
mesh_terms: D000375:Aging / Q000473:pathology*; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism; D004198:Disease Susceptibility / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D012307:Risk Factors; D013057:Spectrum Analysis; D017356:Synchrotrons; D014808:Vitamin D Deficiency / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: D003094:Collagen