Regulation of Calcium‐parathyroid Hormone Feedback in Primary Hyperparathyroidism: Effects of Bisphosphonate Treatment

Abstract

Dichloromethylene bisphosphonate (C12MBP), a powerful inhibitor of bone resorption, was administered to 27 patients with primary hyperparathyroidism. It was given by either intravenous infusion (six patients, 500-100 mg day), or by intramuscular injection (six patients, 100-200 mg/day) or by mouth (15 patients, 1600-2400 mg/day) for 20-180 days. Sustained suppression of bone resorption was observed in all patients, as judged by a fall in the urinary hydroxyproline excretion. In contrast, the hypocalcaemic effect was inconsistent and short-lived, particularly in the patients without overt bone disease. The fall in serum calcium seemed largely to be due to a transient dissociation between bone resorption and bone formation and was associated with increases in circulating parathyroid hormone (PTH). In ten patients given the bisphosphonate orally for 6 months, serum calcium was unchanged but serum PTH was significantly raised. These results suggest that C12MBP may be of use for short-term correction of severe hypercalcaemia due to hyperparathyroidism, particularly in the patients with overt bone disease. However, its long-term use should not be recommended because of increased PTH secretion.

Bisphosphonates: an overview with special reference to alendronate

“…90 Long-term treatment with bisphosphonates often results in the recurrence of hypercalcaemia, as there is a secondary increase in PTH secretion in response to the reduction in serum calcium. 89 Bisphosphonates are, however, useful in treating the bone disease of primary hyperparathyroidism, leading to normalization of markers of bone turnover and maintenance or improvement of bone density.…”

“…88 However, bisphosphonate therapy may be useful in some situations, such as in acute hypercalcaemic crises, when saline rehydration has not normalized serum calcium. 89 Bisphosphonate treatment in primary hyperparathyroidism should, however, be considered a temporary measure prior to surgery. The de®nitive treatment of primary hyperparathyroidism is surgery to remove the parathyroid adenoma or the hyperplastic glands, as the case may be.…”

Primary Hyperparathyroidism of Postmenopausal Women

“…They have been used in more severe HPT (Jansson et al 1991B, Tal & Graves 1996). An increased serum PTH level has been found concomitant with the decreased serum calcium (Adami et al 1990, Schmidli et al 1990, Grotz et al 1998, as would be expected if HPT is related to a decreased calcium control of the secretion. Recently a few new approaches have been attempted.…”

Decrease of serum calcium concentration and lost influence of calcium on parathyroid hormone release in a patient with primary hyperparathyroidism after treatment with diphosphonates

“…Diphosphonates of the first and second generation such as clodronate have shown their efficacy in the treatment of primary hyperparathyroidism, yet the decrease of serum Ca was only short, transient, and secondarily followed by a steady increase of PTH [11][12][13]. The effect of diphosphonates, especially in inhibiting osteoclast-mediated bone resorption by altering osteoclastic function, differentiation, and recruitment is well documented in hypercalcemia of malignancy, steroid-induced osteoporosis, and Paget's disease [14].…”

“…In contrast, the effect of diphosphonates in patients with pHPT suffering from mild or severe hypercalcemia was only short, transient, and combined with an increase in PTH [11][12][13].…”