Inhibition of Diphosphonate-Blocked Bone Mineralization. Evidence That Calcitonin Promotes Mineralization

Abstract

There is much experimental evidence which indicates that calcitonin inhibits bone mineral resorption, but there are few data available in support of the proposal that calcitonin may also promote mineralization. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) administered to immature rats inhibited mineralization as evidenced by widened tibial epiphyseal plates and decreased bone ash to dry weight ratios. Concurrent dosing with salmon calcitonin (SCT) prevented or reversed the EHDP-blocked mineralization in a dose dependent manner. Administration of SCT during the period after EHDP treatment significantly improved mineralization of tibial epiphyseal plates as shown by plate width narrowing and increased uptake of radioactive calcium. These results suggest that SCT increased mineralization in EHDP-treated rats, and provide supportive evidence for the proposal that calcitonin may also promote mineralization, in addition to its well known ability to inhibit bone mineral resorption.

Effects of 1α-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 on bone remodeling

“…9] and rats [10]. On the other hand, it has no activity in promoting bone mineralization in EHDP-treated rats, although one of its metabolites, lc~,24.25-trihydroxyvitamin D:~, is active [12]. On the other hand, it has no activity in promoting bone mineralization in EHDP-treated rats, although one of its metabolites, lc~,24.25-trihydroxyvitamin D:~, is active [12].…”

Effects of elcatonin on plasma and urine electrolytes in infant beagles.

“…In contrast, calcitonin produces hypercalciuria in humans (15)(16)(17)(18) and sheep (19), possibly by its action on renal tubular reabsorption. The fact that the plasma calcium was lowered despite a decrease in calcium excretion suggests that ECT inter feres with bone resorption of calcium and may promote calcium bone deposition (20). In intact puppies, plasma phosphorus decreased and urinary phosphorus excretion tended to increase by ECT, whereas in all TPTX dogs, phosphorus excretion was unaffected or decreased.…”

The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets

“…Discussion EHDP possesses a structure and action similar to inorganic pyrophosphate which is considered to suppress calcification in vivo (Fleisch 1983 (Baxter et al 1974;Bonjour et al 1975). Boris et al (1979) pointed out that the EHDPtreated rat model could also prove useful when searching for compounds which stimulate mine¬ ralization. They also reported that concurrent administration of salmon calcitonin to EHDPtreated rats prevented or reversed the EHDPblocked mineralization, in a dose-dependent man¬ ner, and proposed that calcitonin may also pro¬ mote mineralization, in addition to its well known ability to inhibit bone mineral résorption.…”

“…the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT. In an animal model of human rickets, induced in rats by ethane-f-hydroxy-bl-diphosphonate (EHDP) administration, in large doses, it was found that administration of salmon calcitonin (Boris et al 1979) and [Asu17]eel calcitonin (CT) (Eguchi et al 1982ab) accelerated the calcifica¬ tion. The mechanisms involved in this accelera¬ tion are unknown.…”