Elsevier

Bone

Volume 51, Issue 3, September 2012, Pages 553-562
Bone

Original Full Length Article
Hypophosphatemic rickets is associated with disruption of mineral orientation at the nanoscale in the flat scapula bones of rachitic mice with development,☆☆

https://doi.org/10.1016/j.bone.2012.04.021Get rights and content
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open access

Abstract

Metabolic bone disorders such as rickets are associated with altered in vivo muscular force distributions on the skeletal system. During development, these altered forces can potentially affect the spatial and temporal dynamics of mineralised tissue formation, but the exact mechanisms are not known. Here we have used a murine model of hypophosphatemic rickets (Hpr) to study the development of the mineralised nanostructure in the intramembranously ossifying scapulae (shoulder bone). Using position-resolved scanning small angle X-ray scattering (SAXS), we quantified the degree and direction of mineral nanocrystallite alignment over the width of the scapulae, from the load bearing lateral border (LB) regions to the intermediate infraspinous fossa (IF) tissue. These measurements revealed a significant (p < 0.05) increase in mineral nanocrystallite alignment in the LB when compared to the IF region, with increased tissue maturation in wild-type mice; this was absent in mice with rickets. The crystallites were more closely aligned to the macroscopic bone boundary in the LB when compared to the IF region in both wild type and Hpr mice, but the degree of alignment was reduced in Hpr mice. These findings are consistent with a correlation between the nanocrystallites within fibrils and in vivo muscular forces. Thus our results indicate a relevant mechanism for the observed increased macroscopic deformability in rickets, via a significant alteration in the mineral particle alignment, which is mediated by an altered spatial distribution of muscle forces.

Highlights

► During murine scapulae development, mineral nanoplatelet alignment and content increase faster in the periphery compared to the intermediate region. ► In the rachitic condition, nanoscale mineral orientation and direction are altered together with altered muscle forces and reduced mineralisation. ► Nanostructural mineral parameters may mediate fracture and deformability in rickets via association between muscle forces and mineral alignment.

Abbreviations

Hpr
hypophosphatemic rickets
SAXS
small angle X-ray scattering
LB
lateral border
IF
infraspinous fossa
ENU
N-ethyl-N-nitrosourea
PBS
phosphate buffered saline
χ
predominant direction of orientation
ρ
degree of orientation

Keywords

N-ethyl-n-nitrosourea
X-linked hypophosphatemic rickets
Scanning synchrotron small angle X-ray scattering
Mineralisation
Bone mineral properties

Cited by (0)

Funding sources: Medical Research Council UK; Diamond Light Source Ltd., Diamond House, Oxfordshire, UK; School of Engineering and Material Sciences, Queen Mary University of London, London, E1 4NS, UK; Engineering and Physical Research Council (EPSRC) UK, Swindon, UK.

☆☆

Conflict of interest: all authors have no conflict of interest.