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  Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)

Fratzl-Zelman, N., Gamsjaeger, S., Blouin, S., Kocijan, R., Plasenzotti, P., Rokidi, S., et al. (2020). Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH). Journal of Structural Biology, 211(3): 107556. doi:10.1016/j.jsb.2020.107556.

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 Creators:
Fratzl-Zelman, Nadja, Author
Gamsjaeger, Sonja, Author
Blouin, Stephane, Author
Kocijan, Roland, Author
Plasenzotti, Pia, Author
Rokidi, Stamatia, Author
Nawrot-Wawrzyniak, Kamilla, Author
Roetzer, Katharina, Author
Uyanik, Gokhan, Author
Haeusler, Gabriele, Author
Shane, Elizabeth, Author
Cohen, Adi, Author
Klaushofer, Klaus, Author
Paschalis, Eleftherios P, Author
Roschger, Paul, Author
Fratzl, Peter1, Author              
Zwerina, Jochen, Author
Zwettler, Elisabeth, Author
Affiliations:
1Peter Fratzl, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863294              

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Free keywords: X-linked hypophosphatemia (XLH); bone histology and histomorphometry; bone mineralization density distribution; collagen cross-links, acidic lipids; conventional therapy; periosteocytic lesions; transiliac bone biopsy samples
 Abstract: X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized. We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions. Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated. The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization. Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles. Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

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Language(s): eng - English
 Dates: 2020-06-302020
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.jsb.2020.107556
PMID: 0592
 Degree: -

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Title: Journal of Structural Biology
  Abbreviation : J. Struct. Biol.
Source Genre: Journal
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Publ. Info: San Diego, CA : Elsevier
Pages: - Volume / Issue: 211 (3) Sequence Number: 107556 Start / End Page: - Identifier: ISSN: 1047-8477