Low‐dose prednisone therapy in rheumatoid arthritis: effect on vitamin d metabolism

Abstract

It has long been recognized that treatment with glucocorticoids can produce a significant loss of bone mass (1,2). The mechanism for this steroid-induced bone loss is not fully understood. but is associated with a marked decrease in intestinal calcium absorption and an increased urinary calcium excretion that frequently accompanies administration of supraphysiologic doses of glucocorticoids (3.4).It has been proposed that steroid-induced alterations in vitamin D metabolism are responsible for the decrease in intestinal calcium absorption produced by glucocorticoid therapy. Reports to date have suggested that 25-hydroxyvitamin D (25[OH]D) concentrations are low ( 5 ) or normal in patients treated with corticosteroids (6,7). More importantly, it has been reported that the circulating concentration of 1, 25[OHI7_D). the physiologically active form of vitamin D, is low (8) or normal (7,9-11) in subjects receiving glucocorticoids. These contradictory results are due, in part, to the dosage and length of glucocorticoid administration used in the previous studies. All studies to date have utilired a supraphysiologic dose of glucocorticoid. In order to assess whether long-term administration of low-dose glucocorticoids affects vitamin D metabolism, we measured the circulating concentrations of the vitamin D metabolites, calcium, phosphorus, alkaline phosphatase, and immunorcactive parathyroid hormone (iPTH) in patients with rheumatoid arthritis receiving 5 mg of prednisone per day for up to 6 months (12). Since the study was conducted as a double-blind trial, an age-matched group of patients with rheumatoid arthritis who received placebo served as the control group.Patients and methods. The details of the patient population and study protocol have been previously reported (12). Briefly, 34 patients were initiated into a double-blind trial that lasted 32 weeks. Patients were admitted who were receiving nonsteroidal antiinflammatory drugs including salicylates, or who were receiving a constant dose of gold salts or D-penicillamine for at least I 2 weeks prior to beginning the study. Excluded were patients with active peptic ulcer disease or rectal bleeding, diabetes mellitus, symptomatic idiopathic osteoporosis, or active renal or hepatic disease. Patients who had received intraarticular glucocorticoid injections, vitamin D, or calcium preparations less than 6 weeks prior to entering the study were also excluded. prednisone 24 weeks into the study. The final evaluation of patients in both groups was made at 32 weeks.

Prednisolone-induced Ca2+malabsorption is caused by diminished expression of the epithelial Ca2+channel TRPV6

“…Available data about the effect of glucocorticoids on vitamin D metabolism are, however, inconclusive. Serum levels of 25-hydroxyvitamin D were low in a number of studies (7) and normal in others (39). Serum 1,25(OH) 2 D 3 levels also varied between studies (1, 7, 32).…”

Glucocorticoids differentially regulate expression of duodenal and renal calbindin-D9k through glucocorticoid receptor-mediated pathway in mouse model

“…Suppressed gene expression by GCs may be controlled by the transcriptional factor AP1 (21). The serum level of 1,25-dihydroxyvitamin D 3 was lower in some series and normal in others, and serum calcitriol level was also variable across studies (9,51,58). In addition, Braun et al (8) and Hahn et al (20) found that prednisone had little effect on serum dihydroxylated vitamin D levels in patients, whereas intestinal calcium absorption fell, suggesting that the GC-related impairment in calcium absorption may be independent of vitamin D. Therefore, reduced duodenal CaBP-9k is not due to suppression of vitamin D by Dex but is derived from the activation of GR by Dex attested with GR antagonist.…”

Effects of Voluntary Resistance Exercise and High-protein Snack on Bone Mass, Composition, and Strength in Rats Given Glucocorticoid Injections

“…Glucocorticoid induced osteoporosis is the results of a number of factors that adversely aŠect calcium homeostasis. [26][27][28][29] Systemic eŠects resulting in abnormalities in gonadal hormone secretion, calcium absorption, and renal handling of calcium and speciˆc eŠects of glucocorticoids on bone all contribute to bone loss. 30,31) In this study, bone calcium content and serum ALP activity were not reduced by glucocorticoid injections, although bone weight and protein contents were markedly reduced.…”