The effect of parathyroid hormone (PTH) and 24,25-dihydroxy-vitamin D₃ on adenylyl cyclase of iliac crest biopsies: Diagnostic and prognostic tool for evaluation and treatment of uremic patients

Abstract

The bone adenylyl cyclase (AC) complex of iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (PrHPT) have been investigated. Bone resorption (RS) in uremic patients appears to be related partly to inceased serum parathyroid hormone (s-PTH) levels and to netto PTH-stimulated AC (net PTH-AC) and partly to the uremic condition (as estimated by s-Creatinine) per se. Serum PTH is able to completely desensitize the PTH dependent bone AC in normals in vivo, but only partially in uremic patients. In patients with PrHPT, the bone AC appears to be inert to homologous desensitization. Positive aluminum staining is associated with blunted CT-responsive and low basal AC.

In the combined group of normals and uremic patients, net PTH-AC is (as predicted from human in vitro data and the rat model) inversely related to serum 24,25-diOH-D₃. Net PTH-AC, when corrected for s-24,25-diOH-D₃ levels, correlated well with RS.

The described action of 24,25-diOH-D₃ presents a clearly defined rationale for the use of 24,25-diOH-D₃ concurrently with 1,25-diOH-D₃ to treat renal osteodystrophy: By administering 1,25-diOH-D₃, s-Ca²⁺ and s-PTH will normalize and consequently net PTH-AC diminish. 24,25-diOH-D₃ is then believed to further reduce net PTH-AC and RS. A concomitant alleviation of the uremic condition would eventually ensure the fastest possible restoration of bone structure and function.

Key-words:

• Adenylyl cyclase
• renal osteodystrophy
• PrHPT
• desensitization
• 24,25-diOH-D₃