What is the role of alfacalcidol (1-alphahydroxyl vitamin D) in the treatment of organ transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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1-Hydroxylated vitamin D may be of particular use in clinical situations associated with accelerated bone loss. There is evidence that alfacalcidol increases trabecular BMD and prevents vertebral fracture. In newly postmenopausal women, alfacalcidol at 1 mcg/d prevented the accelerated loss of vertebral BMD over 3 years following the onset of menopause.

In a nontransplant population of patients with established glucocorticoid-induced osteoporosis, Ringe et al reported an impressive 52% relative risk reduction in new fractures over 3 years with alfacalcidol versus parent vitamin D-3. [95] Matched pairs were randomized to 1 mcg alfacalcidol with 500 mg calcium per day (n=103) or 1000 IU of vitamin D-3 with 500 mg calcium per day (n=101). The median percentage increase in spine BMD in the alfacalcidol group (+2.4%) was 4-fold greater than the parent vitamin D group (-0.8%) over 3 years. In addition, alfacalcidol decreased back pain to a greater degree than plain vitamin D-3.

Generally, side effects in both groups were mild, and only 3 patients in the alfacalcidol group and 2 in the vitamin D group had moderate hypercalcemia. Alfacalcidol would appear to be superior to plain vitamin D-3 in the treatment of established glucocorticoid-induced osteoporosis. At 0.5-1 mcg daily, others have found it useful in preservation of spinal bone density in rheumatoid arthritis as well as transplant osteoporosis, although liver and lung transplant recipients responded more favorably than cardiac transplant recipients. [96]

In cardiac transplant recipients, spine and femoral bone loss were decreased with alfacalcidol plus calcium. Moreover, fewer vertebral fractures were seen in alfacalcidol-treated patients, compared with a control group receiving etidronate and calcium Another study by van Cleemput et al found that 0.25-1 mcg/d of oral alfacalcidol begun approximately 2 weeks after cardiac transplantation improved but did not eliminate bone loss compared with oral etidronate. [97]

De Sevaux and colleagues examined vitamin D metabolites in a cohort of 61 renal transplant recipients and found that nearly half of the patients demonstrated abnormal 1,25-D levels for at least 6 months after transplant, the period associated with the steepest decline in BMD. [98] 1,25 –Dihydroxyvitamin D (1,25D) levels were low at transplantation in all patients and remained subnormal in 64% of patients at 3 months and 47% of patients at 6 months after transplant.

After transplant, the intact PTH levels declined rapidly to just above the normal range. From 3 months after transplant, the 1,25-D levels correlated with creatinine clearance.

Renal transplant recipients receiving alfacalcidol (0.25 mcg/d) with calcium over 6 months had diminished bone loss at the LS and trochanter and almost complete prevention of bone loss at the femoral neck.

Although there were unexpected differences in baseline BMD between the treated and untreated groups in this study, additional analysis of the data suggested that these differences could not explain the results. Severe hypercalcemia was slightly more common in the alfacalcidol group, although nearly all such patients had a high-normal calcium at study entry. Urinary calcium was slightly higher also in the alfacalcidol group at 6 months after renal transplant. [98]

In addition, alphacalcidol may prevent fractures due to falls by improving muscle power. [99]

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