title: No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy.
abstract: Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure.
authors.affiliation: Department of Nephrology, University Hospital, Utrecht, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hené
authors.forename: W J
authors.initials: WJ
authors.lastname: Visser
authors.forename: S A
authors.initials: SA
authors.lastname: Duursma
authors.forename: J A
authors.initials: JA
authors.lastname: Raymakers
authors.forename: R J
authors.initials: RJ
authors.lastname: de bos Kuil
authors.forename: E J
authors.initials: EJ
authors.lastname: Dorhout Mees
mesh_terms: D000328:Adult; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000150:complications*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate
chemical_list: D004164:Diphosphonates; D000077268:Pamidronate