Molybdenum (Mo), at high concentrations, induces changes in the epiphy
seal growth plate through its effects on copper (Cu) metabolism but it
is unclear whether or not Mo can induce changes independent of its ef
fects on copper status. To this end, the effect of Mo on longitudinal
bone growth was examined in rats. Dietary Mo was given either as ammon
ium heptamolybdate or as ammonium tetrathiomolybdate, the latter produ
cing a marked Cu deficiency. There was a significant reduction in long
itudinal bone growth in both groups; however, growth plate width was i
ncreased only in the Cu-deficient animals due to an increase in the wi
dth of the zone of transitional/hypertrophic chondrocytes. Both glucos
e 6-phosphate dehydrogenase activity and cell proliferation (assessed
by bromodeoxyuridine incorporation) were markedly decreased in the pro
liferating zone of the growth plate in both Mo-treated groups. These c
hanges were not apparently related to changes in circulating vitamin D
metabolites or insulin-like growth factor-1. The results indicate tha
t excess Mo impairs cell proliferation within the growth plate, wherea
s the effects of copper deficiency are more related to chondrocyte dif
ferentiation. Thus, Mo can induce changes in longitudinal bone growth
which are distinct from those resulting from Cu deficiency.