Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy.
The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.
Ralston
S H
SH
University Department of Medicine, Glasgow Royal Infirmary, Scotland.
Boyce
B F
BF
Cowan
R A
RA
Gardner
M D
MD
Fraser
W D
WD
Boyle
I T
IT
D000328:Adult; D000368:Aged; D001862:Bone Resorption; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D007103:Immobilization; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D010006:Osteoblasts