| Summary: | There is the tendency with time for hard tissues to soften and soft tissues to harden 'With potential pathological consequences. Comparison of the mineral phase in bot.h may' provide novel insight into associated untreatable conditions of aging. The human proximal femur (the most vulnerable skeletal site) from nonfracture (osteoarthritis), fracture (osteoporosis) and normal subjects was examined, together 'With the human neonatal-TMJ and bone from functionally different skeletal locations in the rat, as wen as human dentine; soft tissues included human and sheep aorta, and sheep intervertebral disc and trachea. Histological methods encompassed plain and polarised light microscopy, epi-fluorescence microscopy, laser confocal microscopy with density gradient mapping, histochemistry and immunohistochemistry, together 'With SEM and TEM and EDXmicroanalysis of elements. These were applied to resin-embedded undecalcified sections, cryosectiGus' and mineral particle isolates separated from the tissue by hydrazine or sodium hydroxide digestion, or prepared synthetically. The results support the view that bone mineral does not consist of random uniform crystals. Population of calcified microspheres, about 1Ilm diameter, occurred in sections and isolates, singly, in bridged assemblies (10IlID long) and compressed into irregular domains or rounded macrosphere domains (30llm diameter). Apparently derived from dense nanospheres (50nm diameter) the microspheres are cell fabrications enclosing a filamentous substructure of 5nm beads. They varied with pathology, being larger (l-5Ilm) in osteoarthritis, and smaller (O.5-1Ilm) in osteoporosis, and the extent of their bridging increased in weight-bearing locations relative to non-weight-bearing sites. They generally lacked the uniform electron density and crystal-like nature of synthetic preparations, except in traces which increase with pathology or chemical exposure. There were some differences of degree with calcified microspheres populations in soft tissues. For example the CaIP ratio was more variable (1.17-2.59 cf. 1.52-1.54) while Mg, Si and Fe were regularly associated with both, Mg was particularly abundant in the calcified particles in the aorta and intervertebral disc. They did not permeate the collagen fibres but in their assemblies and convoluted domains looped around them to form a remarkably varied composite. Of special interest in this regard was the periosteum. Known to be as proactive in development of the skeleton, the results suggested it is a key determinant of its mass and maintenance as a periosteumSharpey's fibre-endosteum integrated system, rich in collagen type III that may function as a sensory avenue for musculoskeletal exchange. Contrasting features of this system are considered in osteoporosis, where it seems too tenuous and in osteoarthritis where it seems too robust. It was concluded that in the connective tissues neither the hard inorganic,phase nor the soft collagenous matrix are the homogeneous substances they are regularly portrayed to be. Their partnership in the young is optimal and beneficial in terms of structural strength and metabolic exchange but with age minor discord in this new histological facet to bone biology may lead to major disability and the challenge this presents for an aging populace.
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