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Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)   
Yazarlar
Nadja Fratzl-Zelman
Sonja Gamsjaeger
Stephane Blouin
Roland Kocijan
Pia Plasenzotti
Stamatia Rokidi
Kamilla Nawrot-Wawrzyniak
Katharina Roetzer
Doç. Dr. Gökhan UYANIK
Kastamonu Üniversitesi
Gabriele Haeusler
Elizabeth Shane
Adi Cohen
Klaus Klaushofer
Eleftherios P. Paschalis
Paul Roschger
Peter Fratzl
Jochen Zwerina
Elisabeth Zwettler
Özet
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.
Anahtar Kelimeler
Acidic lipids | Bone histology and histomorphometry | Bone mineralization density distribution | Collagen cross-links | Conventional therapy | Periosteocytic lesions | Transiliac bone biopsy samples | X-linked hypophosphatemia (XLH)
Makale Türü Özgün Makale
Makale Alt Türü ESCI dergilerinde yayımlanan tam makale
Dergi Adı JOURNAL OF STRUCTURAL BIOLOGY
Dergi ISSN 1047-8477
Makale Dili İngilizce
Basım Tarihi 09-2020
Cilt No 211
Sayı 3
Doi Numarası 10.1016/j.jsb.2020.107556