Toward an understanding of the short bone phenotype associated with multiple osteochondromas.

Individuals with multiple osteochondromas (MO) demonstrate shortened long bones. Ext1 or Ext2 haploinsufficiency cannot recapitulate the phenotype in mice. Loss of heterozygosity for Ext1 may induce shortening by steal of longitudinal growth into osteochondromas or by a general derangement of physeal signaling. We induced osteochondromagenesis at different time points during skeletal growth in a mouse genetic model, then analyzed femora and tibiae at 12 weeks using micro-CT and a point-distribution-based shape analysis. Bone lengths and volumes were compared. Metaphyseal volume deviations from normal, as a measure of phenotypic widening, were tested for correlation with length deviations. Mice with osteochondromas had shorter femora and tibiae than controls, more consistently when osteochondromagenesis was induced earlier during skeletal growth. Volumetric metaphyseal widening did not correlate with longitudinal shortening, although some of the most severe shortening was in bones with abundant osteochondromas. Loss of heterozygosity for Ext1 was sufficient to drive bone shortening in a mouse model of MO, but shortening did not correlate with osteochondroma volumetric growth. While a steal phenomenon seems apparent in individual cases, some other mechanism must also be capable of contributing to the short bone phenotype, independent of osteochondroma formation. Clones of chondrocytes lacking functional heparan sulfate must blunt physeal signaling generally, rather than stealing growth potential focally.

[Osteolathyrism. Quantitative-morphological studies on the experimental rat skeletal disease]. / Osteolathyrismus Quantitativ-morphologische Untersuchungen der experimentellen Skeletterkrankung bei der Ratte

In young growing rats, fed the lathyrogenic agent aminoacetonitrile for 3 weeks, characteristic skeletal changes developed resembling the chronic state of osteolathyrism. In both lathyritic and untreated control rats, the femoral head, the distal end of the femur, the proximal tibial end, the thalocalcanean joint and the first lumbar vertebra were investigated using undecalcified thin sections and ground sections. The following methods were employed: quantitative morphometrical analysis of bone structure and bone remodelling of the lumbar vertebra, histochemical demonstration of the composition of polysaccharides, detection of the course of collagenous fibres in cartilage and bone by the polarizing microscope, tetracycline-labelling and fluorescence microscopical determination of epiphyseal longitudinal growth and bone formation activity, photometrical quantification of microradiographies and computer-aided determination of the mineral content of bone.