Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis.

Treatment with plain vitamin D is a nutritional substitute, while the application of alfacalcidol is an active hormonal therapy. Due to strong feedback regulation, plain vitamin D is not activated in the kidney in vitamin-replete patients, while alfacalcidol, having been hydroxylated at position 1, bypasses regulation and increases available amounts of active D-hormone in different target tissues. Nevertheless, a majority of physicians still prescribe plain vitamin D plus calcium as a first-step prevention or even as therapy for glucocorticoid (GC) induced osteoporosis. This article summarizes results of our previous study comparing the therapeutic efficacy of the D-hormone analog alfacalcidol to plain vitamin D in patients with established GC induced osteoporosis with or without vertebral fracture. Patients taking longterm GC therapy were included as well-matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n = 101). The mean bone mineral density (BMD) values at baseline for the 2 groups for alfacalcidol and vitamin D3, respectively, were: lumbar spine T score -3.26 and -3.25; femoral neck -2.81 and -2.84. Rates of prevalent vertebral and nonvertebral fractures were not different between groups. In the 3 year study we observed in the alfacalcidol group as compared with the plain vitamin D group, respectively: a 3 year median percentage increase of BMD at the lumbar spine of 2.4% versus -0.8% (p < 0.0001); a median increase at the femoral neck of 1.2% versus 0.8% (p < 0.006). Likewise observed in the alfacalcidol as compared to the vitamin D group, respectively: a 3 year rate of patients with > or = 1 new vertebral fracture of 9.7% versus 24.8% (risk reduction: 0.61; 95% CI 0.24 to 0.81; p = 0.005); a 3 year rate of patients with > or = 1 new nonvertebral fracture of 15% versus 25% (risk reduction: 0.41; 95% CI -0.06 to 0.68; p = 0.081); a 3 year rate of patients with > or = 1 new fracture of any kind of 19.4% versus 40.6% (risk reduction: 0.52; 95% CI 0.25 to 0.71; p = 0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group (p < 0.0001). Generally, side effects in both groups were mild, and only 3 patients in the alfacalcidol group and 2 patients in the vitamin D group had moderate hypercalcemia. We conclude that alfacalcidol plus calcium is highly superior to plain vitamin D3 plus calcium in the treatment of established GC induced osteoporosis, and the latter should no longer be used as monotherapy.

RCT Entities:   Population Interventions Outcomes