Prevention of corticosteroid-induced osteoporosis by alfacalcidol

Abstract

We studied the effect of alphacalcidol (1-alpha-hydroxycholecalciferol) on bone metabolism in patients who were placed on glucocorticoid therapy. We selected 41 women (age: 32-52 yrs) who were recently diagnosed with systemic lupus erythematodes, multiple sclerosis, rheumatoid arthritis or asthma bronchiale. Patients did not have other disease or take drugs known to influence bone metabolism. Patients were randomly enrolled into two groups and were given 5-25 mg prednisone daily. After 4 weeks, group A (n = 21) received 0.5-1.0 microgram (mean = 0.54 +/- 0.03 microgram) alphacalcidol and group B (control; n = 20) was given 500 mg calcium daily for three years. There were no significant differences in age and steroid doses between groups. Serum calcium (Ca), osteocalcin (OC), collagen I C-terminal propeptide (PICP), parathyroid hormone (PTH), and urinary calcium and deoxypyridinoline crosslink excretion (DPD) were measured before corticosteroid administration, and before alphacalcidol or calcium treatment as well as 6 weeks, 6 months, and 1, 2, and 3 years later. Bone mineral density (BMD) was examined before treatment and 6 months, 1, 2, and 3 years later by DEXA and SPA. OC and PICP decreased significantly after 4 weeks on steroid in both groups and increased in group A but not in group B after 6 weeks of treatment with alphacalcidol and remained unchanged for 3 years. Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A, but not in group B, after 6 weeks on alphacalcidol. Serum Ca, urinary Ca, and DPD did not change significantly in either group during the study period. Lumbar spine and femoral neck BMD were significantly reduced in group B after 6 months and 1 year, respectively, and continued to decrease during the study, while no significant change in group A was observed. BMD of the radius did not change in either group for 2 years but there was a significant reduction by the third year in group B. Based on these results, alphacalcidol treatment appears to be effective in preventing glucocorticoid-induced bone loss in these patients by reducing secondary hyperparathyroidism and stimulating bone formation.

Effects of Alfacalcidol on Cancellous and Cortical Bone Mass in Rats Treated with Glucocorticoid: A Bone Histomorphometry Study

“…Meta-analyses and a systematic review in western countries have revealed the efficacy of ALF for maintaining the lumbar BMD and reducing the incidence of vertebral fractures in patients with GCinduced osteoporosis ( 4 -6 ). A randomized controlled E-mail: jiwamoto@sc.itc.keio.ac.jp trial showed the effect of ALF on bone metabolism in patients who were on GC treatment; ALF reduced the severity of hyperparathyroidism and stimulated bone formation ( 7 ). However, the effect of ALF on cancellous and cortical bone mass, as well as on bone formation and bone resorption has not necessarily been established in GC-treated patients.…”

Bone health in systemic lupus erythematosus

“…However, three studies have examined the role of activated vitamin D (calcitriol [48,49] and alfacalcidol [50]). In two of these studies [48,50], activated vitamin D was compared with calcium.…”

“…However, three studies have examined the role of activated vitamin D (calcitriol [48,49] and alfacalcidol [50]). In two of these studies [48,50], activated vitamin D was compared with calcium. In a randomized, double-blind, placebo-controlled study of calcitriol, 81 premenopausal women with SLE taking chronic glucocorticoid therapy were randomly assigned to one of three groups: 1) 0.5 μg of calcitriol and 1200 mg of calcium daily; 2) 1200 mg of calcium and placebo calcitriol; and 3) both placebo calcitriol and placebo calcium.…”

“…The authors concluded that HRT but not calcitriol could prevent bone loss in young hypogonadal women taking chronic glucocorticoids. Alfacalcidol was studied in 41 women with various infl ammatory conditions, including SLE, recently started on glucocorticoids [50]. Patients were randomly assigned to one of two groups and administered either 0.5 to 1.0 mg of alfacalcidol or 500 mg of calcium for 3 years.…”

Neurological Osteoporosis in Disabilities

“…Low testosterone alone in these populations does not explain bone loss and no clear effect of smoking or alcohol abuse to decreased bone mass could be established (Weinstock-Guttman et al, 2004). Glucocorticoid (GC)-induced osteoporosis (OP-GC) is the main type of secondary osteoporosis (Canalis et al, 2004;Canalis et al, 2007;Lakatos et al, 2000;Mazziotti et al, 2006;Schwid et al, 1996;Shuhaibar et al, 2009). The mechanism is that excess GC causes a rapid and significant damage to bone quality.…”