Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength

ABSTRACT Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteopo...

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Published in:Journal of bone and mineral research 2019-06, Vol.34 (6), p.1101-1114
Main Authors: Beck‐Cormier, Sarah, Lelliott, Christopher J, Logan, John G, Lafont, David T, Merametdjian, Laure, Leitch, Victoria D, Butterfield, Natalie C, Protheroe, Hayley J, Croucher, Peter I, Baldock, Paul A, Gaultier‐Lintia, Alina, Maugars, Yves, Nicolas, Gael, Banse, Christopher, Normant, Sébastien, Magne, Nicolas, Gérardin, Emmanuel, Bon, Nina, Sourice, Sophie, Guicheux, Jérôme, Beck, Laurent, Williams, Graham R, Bassett, J H Duncan
Format: Article
Language:English
Subjects:
ANIMAL MODELS (GENETIC ANIMAL MODELS)
Bone mass
BONE MATRIX (MATRIX MINERALIZATION)
Bone mineral content
Bone mineral density
Bone strength
Calcium phosphates
DISORDERS OF CALCIUM/PHOSPHATE METABOLISM (OTHER)
GENETIC RESEARCH (HUMAN ASSOCIATION STUDIES)
Genetics
Life Sciences
Mineralization
Original
ORTHOPAEDICS (BIOMECHANICS)
Ossification
Osteoporosis
Phosphate transporter
Quality
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Summary:ABSTRACT Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2–/– mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2–/– mice: yield load (–2.3 SD), maximum load (–1.7 SD), and stiffness (–2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild‐type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.3691