Oral administration of
manganese (Mn) to young rats results in morphologic changes in the growth plate histologically resembling
rickets. Previous investigations have indicated that one important factor in the development of Mn
rickets is
phosphate depletion, because of the precipitation of insoluble
manganese phosphate in the gut. In the present study, the morphologic and biochemical changes in
rickets induced by
phosphate (P) depletion per se as well as in florid and healing Mn
rickets were investigated. Rachitic changes were induced in young rats by giving dietary Mn (2%) or by
phosphate depletion (0.02% P) for 25 days. The rachitic changes of the proximal tibial growth plate were quantitated with the use of stereologic methods. In addition, the growth plates were dissected into one upper and one lower part and
proteoglycans were separately extracted with 4 M
guanidine hydrochloride and purified by ultracentrifugation. In rats given
phosphate in more than equimolar amounts relative to Mn, the rachitic changes were abolished. When rats with florid Mn
rickets were given standard rat food, containing 1% P, rapid healing ensued. Moreover, similar rachitic changes were obtained by
phosphate depletion alone.
Proteoglycans from the lowermost tissue portion of rachitic growth plates readily formed aggregates with
hyaluronic acid and also contained larger
chondroitin sulphate chains than controls. Upon healing, these changes tended to normalize. The data support the concept that
phosphate depletion is crucial in the pathogenesis of Mn
rickets. Also, it seems that the biochemical changes in different forms of
rickets are of a similar kind, which further underlines the importance of
proteoglycans in enchondral bone formation.