Importance of alfacalcidol in clinical conditions characterized by high rate of bone loss.
In postmenopausal osteoporosis, the administration of alfacalcidol to women resulted in an increase in trabecular bone mineral density (BMD), prevention of cortical bone loss, and a significant reduction in the incidence of further vertebral fractures. There is now robust evidence that alfacalcidol may be particularly active in conditions characterized by an increased rate of bone loss. Alfacalcidol 1 microg/day fully prevented vertebral bone loss over 3 years in women after the first year of menopause. In a large cohort of individuals starting treatment with high dose corticosteroid (CS, 46.6 mg equivalent prednisolone per day), the spinal bone loss observed in untreated patients was fully prevented by administration of 1 microg/day alfacalcidol. In patients with established CS-induced osteoporosis, with or without prevalent vertebral fractures, 1 microg/day of alfacalcidol, given for 3 years, increased lumbar spine density, reduced back pain, and showed a significant reduction in the rate of new vertebral fractures, compared to native vitamin D. In cardiac transplant recipients, alfacalcidol and calcium reduced spinal and femoral bone loss, compared to a control group treated with etidronate and calcium. Alfacalcidol-treated patients experienced fewer new vertebral fractures over the 2-year followup. When alfacalcidol and vitamin D3 were compared in elderly women with radiologic evidence of vertebral fracture, fractional calcium absorption was increased after 3 months with alfacalcidol but was unchanged with vitamin D3. In a recent metaanalysis of 14 studies of native vitamin D and 19 studies of D-hormone analogs (alfacalcidol and calcitriol), the D-analogs exerted a higher preventive effect on bone loss and fracture rates in patients with no exposure to CS. In head-to-head studies comparing D-analogs and native vitamin D in patients receiving CS, this metaanalysis identified significant effects favoring D-analogs for femoral neck BMD and spinal fractures. In conclusion, improvement in bone turnover, increase in BMD, and reduction in fracture rates have been described during alfacalcidol treatment in situations characterized by a high rate of bone loss, including CS-induced osteoporosis, early postmenopausal bone loss, and organ transplant. Compared to plain vitamin D, alfacalcidol exerts higher bone-protective effects, thus allowing the doses to be minimized and lowering the risk of adverse effects, including hypercalcemia.
Reginster
Jean-Yves
JY
Bone and Cartilage Metabolism Research Unit, University of Liège, Liège, Belgium. jyreginster@ulg.ac.be
Lecart
Marie-Paule
MP
Richy
Florent
F
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000627:therapeutic use*; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000517:prevention & control; D016103:Spinal Fractures / Q000517:prevention & control; D014180:Transplantation / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; C008088:alfacalcidol