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Micrometer-Sized Magnesium Whitlockite Crystals in Micropetrosis of Bisphosphonate-Exposed Human Alveolar Bone

Journal article
Authors Furqan A. Shah
B. E. J. Lee
J. Tedesco
Cecilia Larsson Wexell
C. Persson
Peter Thomsen
K. Grandfield
Anders Palmquist
Published in Nano Letters
Volume 17
Issue 10
Pages 6210-6216
ISSN 1530-6984
Publication year 2017
Published at Institute of Clinical Sciences, Department of Biomaterials
Pages 6210-6216
Language en
Keywords Osteocyte lacuna, mineralization, micropetrosis, magnesium, whitlockite, bisphosphonates, beta-tricalcium phosphate, stabilizing impurity, in-vivo, mg, hydroxyapatite, beta-ca3(po4)2, homeostasis, osteocytes, apoptosis, apatite
Subject categories Biomaterials Science


Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bi-sphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed "micropetrosis". Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of similar to 80 nm to similar to 3 mu m wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)(2)(PO4)(12)] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

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