1 alpha-Hydroxy-vitamin D2: a new look at an 'old' compound

Area of Science:

• Endocrinology
• Nephrology
• Pharmacology

Background:

• Calcitriol effectively suppresses parathyroid hormone (PTH) in hemodialysis patients but has a narrow therapeutic index.
• There is a need for vitamin D sterols that suppress PTH with less risk of hypercalcemia.

Purpose of the Study:

• To review evidence supporting 1 alpha-hydroxy-vitamin D2 (1 alpha-D2) as a safer alternative to calcitriol.
• To evaluate the efficacy and safety profile of 1 alpha-D2 in various preclinical and clinical models.

Main Methods:

• Review of existing studies on 1 alpha-D2 in vitamin D-deficient and normal rats.
• Examination of data from osteopenia models (steroid-induced and ovariectomy-induced).
• Analysis of studies in osteoporotic women and preliminary data from hemodialysis patients.

Main Results:

• In rats, 1 alpha-D2 is equipotent to 1 alpha-D3 in deficient states but less toxic at high doses.
• 1 alpha-D2 is as effective or more effective than 1 alpha-D3 in preventing bone loss with less hypercalciuria.
• Studies in women and hemodialysis patients show minimal hypercalciuria and PTH suppression with minimal effects on calcium and phosphorus.

Conclusions:

• 1 alpha-D2 demonstrates a favorable safety profile compared to calcitriol and 1 alpha-D3, particularly regarding hypercalciuria.
• Preliminary data suggest 1 alpha-D2 is effective in suppressing PTH in hemodialysis patients with secondary hyperparathyroidism.
• 1 alpha-D2 warrants consideration as a therapeutic agent for secondary hyperparathyroidism in end-stage renal disease.