Studies in a Hemodialysis Patient Indicating that Calcitriol May Have a Direct Suppressive Effect on Bone

Abstract

Calcitriol putatively suppresses bone activity by decreasing parathyroid hormone (PTH) levels. Results of studies in a 52-year-old female maintenance hemodialysis patient suggest that calcitriol may also have a direct suppressive effect on bone. The PTH-calcium relationship was evaluated through the use of low (1 mEq/1) and high (4 mEq/1) calcium hemodialyses that were performed before the initiation of calcitriol treatment, at the end of 6 weeks of thrice-weekly intravenous calcitriol administration, and 6 weeks after the discontinuation of calcitriol. During the low-calcium dialysis, serum calcium decreased more rapidly and to a greater magnitude after calcitriol treatment despite no appreciable difference in basal and maximally stimulated PTH levels; during the high-calcium dialysis, calcitriol treatment resulted in a more rapid increase in serum calcium despite no appreciable difference in basal and maximally suppressed PTH levels. Discontinuation of calcitriol resulted in responses to the low and high calcium dialyses that were similar to those observed before calcitriol treatment. In conclusion, the results suggest that calcitriol may have a direct suppressive effect on bone that is independent of PTH.

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

“…Similar results were reported by Cardinal et al (33). In maintenance hemodialysis patients, the maximal PTH value is often 10 to 20 times greater than normal (70,72,73) and sometimes even greater (74). In a study of vitamin D deficiency in dogs, maximal PTH values increased by more than five-fold as vitamin D deficiency evolved during a 2-yr period (19).…”

Alfacalcidol Therapy Biphasically Modifies the Relationship between the Plasma Levels of Intact PTH and Osteocalcin in Dialysis Patients

“…We generally agree with the opinion advocated by Pahl et al [1] and Ureña et al [2] that calcitriol might directly suppress bone metabolism in dialysis patients. Experimental studies have supported their assumption.…”

The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats

“…Consistent with this observation, preclinical and clinical data have suggested that cinacalcet may reduce bone turnover, tissue fibrosis, bone loss and fractures (Lien et al, 2005; Cunningham et al, 2005). Likewise, some evidence suggests that calcitriol can ameliorate osteitis fibrosa (Slatopolsky et al, 1984; Andress et al, 1989), while other clinical studies show either no or detrimental effects on bone remodeling (Costa et al, 2003; Pahl et al, 1995).…”

“…Moreover, preclinical (Wada et al,1998) and clinical (Lien et al, 2005; Cunningham et al, 2005) evidence suggests that calcimimetics improve bone health, including reducing the incidence of fractures. Some clinical data show that calcitriol may influence bone remodeling and ameliorate osteitis fibrosa (Slatopolsky et al, 1984; Andress et al, 1989), although other studies have shown either no or detrimental effects on bone remodeling (Costa et al, 2003; Pahl et al, 1995).…”