Effect of oral 1,25‐dihydroxyvitamin D and calcium on glucocorticoid‐induced osteopenia in patients with rheumatic diseases

Abstract

Twenty-three rheumatic disease patients with glucocorticoid-induced osteopenia (defined by measurement of forearm bone mass) completed an 18-month double-blind, randomized study to assess the effect of oral calcium and 1,25-dihydroxyvitamin D ( 1,25-OH2D) or calcium and placebo on bone and mineral metabolism. Intestinal 47Ca absorption was increased (P < 0.05) and serum parathyroid hormone levels were suppressed (P < 0.01) by 1,25-OH2D (mean dose 0.4 pgl day); however, no significant gain in forearm bone mass occurred, and bone fractures were frequent in both groups. In the 1,25-OH2D group, histomorphometric analysis of iliac crest biopsy specimens demonstrated a decrease in osteoclasts/mm2 of trabecular bone (P < 0.05) and parameters of osteoblastic activity (P < 0.05), indicating that 1,25-OH2D reduced both bone resorption and formation. We conclude that 1,25-OH2D should not be used for treatment of glucocorticoidinduced osteopenia. Since patients receiving calcium and placebo did not exhibit a loss of forearm bone mass, elemental calcium supplementation of 500 mg daily might be useful to maintain skeletal mass in patients receiving long-term glucocorticord therapy. Submitted for publication March 27, 1984; accepted in revised form July I I , 1984. Oral administration of glucocorticords in humans results in severe osteopenia caused by several mechanisms (1-3). Histologic studies of bone in humans receiving glucocorticoids demonstrate decreased bone formation (4-6) and increased numbers of osteoclasts and osteoclast-resorbing surfaces (5-7). The decrease in formation rate probably represents a direct effect of glucocorticoids on osteoblasts. Specifically, glucocorticoids decrease the recruitment of progenitor cells to osteoblasts and the synthesis of collagen and noncollagen protein by preexisting osteoblasts (8,9).The mechanism by which glucocorticoids increase bone resorption is more controversial. In vitro, glucocorticoids inhibit osteoclast activity (3, lo). However, in vivo, glucocorticoids greatly decrease intestinal calcium absorption (2,11,12) and may stimulate parathyroid hormone (PTH), thus providing an indirect stimulus to osteoclastic activity (6,13

Treatment of established osteoporosis: a systematic review and cost-utility analysis

“…A total of 88 RCTs were identified by this means. A further eight relevant trials were identified from the reference lists of identified trials and relevant review articles, [61][62][63][64][65][66][67][68] and an additional four by hand-searching only. [69][70][71][72] No trials were identified by pharmaceutical companies that had not been identified by other means.…”

“…63,64,[117][118][119][120][121][122][123] These trials included those in which patients in both the intervention and control groups received calcium and/or vitamin D in comparable doses. Those studies in which vitamin D derivatives were compared with another active intervention are discussed later (page 36).…”

Urolithiasis in pediatric patients with acute lymphoblastic leukemia

“…The finding of calcium stones and the increased risk of urolithiasis in patients treated with glucocorticoids suggest that the mechanism of stone formation is steroid-induced bone demineralization followed by hypercalciuria. [8][9][10][11][12][13] Risk factors for recurrence…”

“…7 However, in the setting of glucocorticoid therapy, vitamin D and calcium supplementation may cause hypercalcemia [8][9][10] and increased urinary calcium excretion with consequent risk for urolithiasis. [11][12][13] Little is known about the incidence, timing, and causes of urolithiasis in children with ALL and the composition of stones. In this study, we define the incidence, timing, clinical consequences, risk factors, and outcome of urolithiasis, as well as the stone composition in children with ALL.…”

Use of a Computerized Order Set to Increase Prescription of Calcium and Vitamin D Supplementation in Patients Receiving Glucocorticoids

“…1 These recommendations are based on the safety profile of moderately dosed calcium and vitamin D and studies demonstrating that (1) oral glucocorticoids can lead to rapid bone loss within the first 3 months of glucocorticoid use, 2 and (2) while the risk of GIOP increases with the cumulative glucocorticoid dose, there is no dose of glucocorticoids that does not accelerate bone loss or increase fracture risk; 3,4 (3) several randomized controlled trials have shown that the administration of calcium and vitamin D in patients undergoing glucocorticoid therapy can prevent early bone loss. [5][6][7] In contrast, recommendations regarding the use of bisphosphonates are individualized based on risk factors and childbearing potential.…”