title: Fragility fractures in men with idiopathic osteoporosis are associated with undermineralization of the bone matrix without evidence of increased bone turnover.
abstract: The pathogenesis of primary osteoporosis in younger individuals is still elusive. An important determinant of the biomechanical competence of bone is its material quality. In this retrospective study we evaluated bone material quality based on quantitative backscattered electron imaging to assess bone mineralization density distribution (BMDD) in bone biopsies of 25 male patients (aged 18-61 years) who sustained fragility fractures but were otherwise healthy. BMDD of cancellous bone was compared with previously established adult reference data. Complementary information was obtained by bone histomorphometry. The histomorphometric results showed a paucity of osteoblasts and osteoclasts on the bone surface in the majority of patients. BMDD revealed a significant shift to lower mineralization densities for cancellous bone values: CaMean (weighted mean Ca content, -5.9%), CaPeak (mode of the BMDD, -5.6%), and CaHigh (portion of fully mineralized bone, -76.8%) were decreased compared to normative reference; CaWidth (heterogeneity in mineralization, +18.5%) and CaLow (portion of low mineralized bone, +68.8; all P < 0.001) were significantly increased. The shift toward lower mineral content in the bone matrix in combination with reduced indices of bone formation and bone resorption suggests an inherent mineralization defect leading to undermineralized bone matrix, which might contribute to the susceptibility to fragility fractures of the patients. The alteration in bone material might be related to osteoblastic dysfunction and seems fundamentally different from that in high bone turnover osteoporosis with a negative bone balance.
authors.affiliation: Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department Hanusch Hospital, 1140 Vienna, Austria. nadja.fratzl-zelman@osteologie.at
authors.forename: Nadja
authors.initials: N
authors.lastname: Fratzl-Zelman
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Misof
authors.forename: Kamilla
authors.initials: K
authors.lastname: Nawrot-Wawrzyniak
authors.forename: Sarah
authors.initials: S
authors.lastname: Pötter-Lang
authors.forename: Christian
authors.initials: C
authors.lastname: Muschitz
authors.forename: Heinrich
authors.initials: H
authors.lastname: Resch
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zwettler
mesh_terms: D000293:Adolescent; D000328:Adult; D001696:Biomechanical Phenomena; D001706:Biopsy; D015519:Bone Density / Q000502:physiology; D001857:Bone Matrix / Q000503:physiopathology*; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000473:pathology; D002113:Calcification, Physiologic / Q000502:physiology*; D050723:Fractures, Bone / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000150:complications* / Q000503:physiopathology*; D012189:Retrospective Studies; D055815:Young Adult