Premium
Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy
Author(s) -
Ralston Stuart H.,
Boyce Brendan F.,
Cowan Robert A.,
Gardner Mary D.,
Fraser William D.,
Boyle Iain T.
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040115
Subject(s) - endocrinology , medicine , malignancy , bone resorption , pathogenesis , primary hyperparathyroidism , osteoclast , resorption , osteoblast , calcium , hyperparathyroidism , bone remodeling , chemistry , receptor , in vitro , biochemistry
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 < 0.002), degree of immobility ( r = 0.87, p < 0.002), and level of urinary cyclic AMP excretion ( r = 0.60, p < 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 < 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.