The production of heterotopic calcification by certain chemical salts

Abstract

The subcutaneous injection of small quantities of LaCl3 and CeCl3 was followed by calcification of the dorsal fascia in mice. The calcification reaction was shown by separate positive histochemical tests for calcium ions (the chloranilic acid reaction) and phosphate (the von Kossa reaction). The injection of cadmium chloride and stannous salts caused damage to and a positive von Kossa reaction in the fibres of the panniculus carnosus muscle. The significance and specificity of the histochemical tests was determined by X-ray microprobe analysis of tissues injected with the above salts and other salts known to cause either combined chloranilic acid and von Kossa positive reactions or isolated von Kossa positive reactions in mouse skin. The pathogenesis of the reactions produced by LaCl3, CeCl3 and KMnO4 was studied by applying histochemical tests to tissues recovered at timed intervals after injection. The reactions produced by LaCl3 and CeCl3 were similar and occurred in the dorsal fascia with positive VK reactions occurring first after 18 followed by positive CA reactions after 24 hr. The distribution of these reactions suggested a haematogenous origin for the constituent ions. The injection of KMnO4 in a much higher dose caused damage to the skin and particularly the fibres of the panniculus carnosus muscle. In contrast to the other salts, the calcific reaction occurred in association with these fibres, showing equally positive von Kossa and chloranilic acid reactions from the early stages.

Tomographic Imaging of Collagen-Mineral Interaction: Implications for Osteogenesis Imperfecta

“…* or the mineralized patches of skin found in calciphylaxis or calcergy. [3][4][5] In these instances, the collagen-mineral composite is marked by a brittle nature rather than by the hardness and strength of normally calcified tissues. This marked fragility frequently leads to complications of skeletal growth or other possibly severe consequences in calcification.…”

Lanthanide‐induced calcergy

“…S E L Y E (1962) indicated that the trichlorides of the rare earth elements lanthanum and cerium were capable of causing local calcification when injected into the subcutaneous tissues of the rat (local calcergy). This observation was confirmed for the mouse by McClure (1980). Haley and Upham (1963) have also demonstrated calcium salts in granulomas induced by the intradermal injection of several lanthanides in the guinea-pig.…”

Metal deposition in calcific uremic arteriolopathy

“…17,18 Subsequently, McClure et al tested the calcergenic effect of lanthanides (including GdCl 3 ) in the mouse, and obtained a similar reaction pattern. 41 Johansson et al also have demonstrated that intravenous injections of lanthanum chloride (LaCl3) produces hypercalcemia and hyperphosphatemia, a milieu proven to be conducive to the deposition of calcium phosphate. 42 While these reports, in aggregate, indicate that calcification and lesions of CUA may be induced by injection of metal salts into the skin, a more detailed understanding of the mechanism of CUA in vivo in humans including an analysis of tissue content of metals has never been performed previously.…”