title: Osteocyte deficiency in hip fractures.
abstract: Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures.
authors.affiliation: Department of Internal Medicine, Hospital U.M. Valdecilla, IFIMAV, University of Cantabria, Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Delgado-Calle
authors.forename: Jana
authors.initials: J
authors.lastname: Arozamena
authors.forename: Raúl
authors.initials: R
authors.lastname: García-Renedo
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ibarbia
authors.forename: María A
authors.initials: MA
authors.lastname: Pascual-Carra
authors.forename: Jesús
authors.initials: J
authors.lastname: González-Macías
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006620:Hip Fractures / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D001798:Blood Proteins; C000717427:FGF23 protein, human; D011506:Proteins; C013247:sclerotin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human