In vivo mobilization of bone calcium in thyroparathyroidectomized rats by 1 alpha, 25-dihydroxycholecalciferol (calcitriol) and related compounds.

Calcitriol, 0.5 microgram/rat, given subcutaneously (sc), did not mobilize 45Ca from bone in intact, pre-labeled rats, but caused significant elevation of serum radioactivity in thyroparathyroidectomized (TPTX) rats. The response to calcitriol in TPTX rats was dose-dependent with significant activity at sc doses of 40 ng/rat and above when measured at 18 hours after dosing.

Inhibition of diphosphonate-blocked bone mineralization. Evidence that calcitonin promotes mineralization.

There is much experimental evidence which indicates that calcitonin in hibits 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.

Evidence for the promotion of bone mineralization by 1alpha,25-dihydroxycholecalciferol in the rat unrelated to the correction of deficiencies in serum calcium and phosphorus.

Concurrent administration of 1alpha,25-dihydroxycholecalciferol [1alpha,25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1alpha-droxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1alpha,25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths.

Relative activities of some metabolites and analogs of cholecalciferol in stimulation of tibia ash weight in chicks otherwise deprived of vitamin D.

Nine metabolites and analogs of cholecalciferol (CC) were tested for ability to increase tibia ash weight in chicks otherwise deprived of vitamin D. All of the compounds promoted bone mineralization in a linear log dose-response relationship. The maximal response obtained for any compound was an approximate doubling in bone ash weight compared to vehicle-treated controls.