Effect of Chronic Corticosteroid Administration on Diaphyseal and Metaphyseal Bone Mass

150

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

Section: Methodssupporting

confidence: 89%

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

Dykman

Haralson

Gluck

et al. 1984

150

“…We have previously used single photon absorptiometry to measure appendicular bone mineral mass in normal individuals and rheumatic disease patients (7)(8)(9)(10). Measurements at diaphyseal and metaphyseal sites of the radius demonstrate a constant relationship between bone mineral mass at the diaphyseal site and that at the metaphyseal site, both in normal individuals and in most patients with conditions associated with osteopenia (for example, idiopathic osteoporosis).…”

mentioning

confidence: 99%

“…Measurements at diaphyseal and metaphyseal sites of the radius demonstrate a constant relationship between bone mineral mass at the diaphyseal site and that at the metaphyseal site, both in normal individuals and in most patients with conditions associated with osteopenia (for example, idiopathic osteoporosis). However, in osteopenia associated with glucocorticoid therapy, there is a greater loss of metaphyseal mass (MM) than diaphyseal mass (DM), and the DM:MM ratio increases (7)(8)(9)(10). A combination of factors may account for this observation.…”

mentioning

confidence: 99%

Evaluation of factors associated with glucocorticoid‐induced osteopenia in patients with rheumatic diseases

Dykman

Gluck

Murphy

et al. 1985

250

In 161 ambulatory rheumatic disease patients receiving long-term prednisone therapy, diaphyseal mass (DM) and metaphyseal mass (MM) of the forearm were measured by single photon absorptiometry, and bone radiographs were reviewed when available. Multivariate analysis of treatment and patient characteristics demonstrated that glucocorticoid-induced osteopenia (defined as an elevated DM:MM ratio) and bone fractures occurred with similar frequency in patients of each sex, in whites and blacks, in patients with various rheumatic diseases, and in patients receiving different regimens of prednisone therapy. However, large cumulative doses of prednisone were associated with elevated DM:MM ratios as well as with bone fractures, and menopause or age 2250 years (males or females) was associated with bone fractures. We conclude that longterm therapy with various prednisone regimens results in glucocorticoid-induced osteopenia and fractures. This affect is cumulative, occurs in all patient groups, and results in more bone fractures in certain groups.It has long been recognized that long-term administration of oral glucocorticoids can result in a significant loss of bone mass (1-3). The degree of loss is more severe in areas of the skeleton with a high content of trabecular bone, such as vertebrae and ribs. It is less striking in the diaphyses of long bones, which consist primarily of compact cortical bone (4-6).We have previously used single photon absorptiometry to measure appendicular bone mineral mass in normal individuals and rheumatic disease patients (7-10). Measurements at diaphyseal and metaphyseal sites of the radius demonstrate a constant relationship between bone mineral mass at the diaphyseal site and that at the metaphyseal site, both in normal individuals and in most patients with conditions associated with osteopenia (for example, idiopathic osteoporosis). However, in osteopenia associated with glucocorticoid therapy, there is a greater loss of metaphyseal mass (MM) than diaphyseal mass (DM), and the DM:MM ratio increases (7-10). A combination of factors may account for this observation. First, the metaphyseal site contains a higher proportion of trabecular bone (>25%) than the diaphyseal site (-5%) (1 1). Second, the metaphyseal site has a greater surface area than the diaphyseal site, and endosteal resorption of cortical bone may be more easily measured at the metaphyseal site.Since measurement of DM:MM ratios provides a simple, inexpensive, and rapid method of identifying patients with glucocorticoid-induced osteopenia, we have measured these ratios in 161 patients with various rheumatic diseases treated with long-term glucocorticoid therapy. This report evaluates whether different glucocorticoid treatment regimens and patient characteristics are associated with glucocorticoid-induced osteopenia and bone fractures.

“…There is substantial evidence indicating that glucocorticoids induce osteoporosis in patients receiving treatment for RA (1-3,10,13-16, and Nagant de Deuxchaisnes C: personal communication) and for other diseases (16)(17)(18)(19). Nevertheless, it is still unclear to what extent the dosage or the duration of treatment is related to the degree of bone loss.…”

mentioning

confidence: 99%

The effect of glucocorticoids on bone mass in rheumatoid arthritis patients. Influence of menopausal state

Als

Gotfredsen

Christiansen

1985

103