Morphogenesis of Floating Bone Segments: A Legacy of Serial Tensile Cross-Strut Microdamage in Trabecular Disconnection “Crumple Zones”?

Trabecular bone disconnection “hotspots” of real termini (ReTm) previously mapped as loci of weakness in the female aging spine and hip may be a source of free-floating cancellous segments found in the medullary space using a bespoke, thick slice histological method for identifying ReTm. A factor in their origin is apparently microdamage proliferation (differentiated by en bloc silver staining) with occasional callus moderation. Validation of similar “floating segments” (FS) in the ex-breeder rat suggested a pilot model for a potentially common phenomenon. Following marrow elution and density fractionation of the isolated floating segments from the whole proximal rat femora, scanning electron microscopy (SEM) and elemental microanalysis (EDS) was performed. The eluent contained numbers of vertically truncated, laterally branched floating segments (acute severance of sequential tensile cross-struts, causing chronic compression overload of axial-struts, with ii) inadequate stabilising callus, facilitating ReTm stacking into predetermined, substructural “crumple zones” of force containment, spheroidal attrition and particulate dissociation. As a catabolic outcome of altered tensile and hormonal influence, FS number may add a novel variable to cancellous bone kinetics particularly in women of relevance to fracture predisposition.

A novel mutation in COL1A2 leads to osteogenesis imperfecta/Ehlers-Danlos overlap syndrome with brachydactyly

Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.