The Course of Biochemical Parameters of Bone Turnover during Treatment with Corticosteroids

Abstract

The mechanisms by which glucocorticoids cause osteopenia are incompletely understood. It is generally accepted that bone formation is depressed during corticosteroid treatment, but the cause of the ongoing bone resorption is less clear. Secondary hyperparathyroidism and changes in vitamin D metabolism are thought to play a role. This is based mostly on data from cross-sectional studies in heterogeneous patient groups. We, therefore, studied longitudinally the course of biochemical parameters and the hormones influencing bone turnover in a homogeneous group of 10 euthyroid patients with Graves' ophthalmopathy, all euthyroid for at least 1 yr before, during, and after a 12-week course of prednisone. Bone formation was depressed as reflected by a fall in serum osteocalcin (3.0 +/- 2.1, 1.7 +/- 1.1, and 2.4 +/- 1.9 micrograms/L at weeks 0, 4, and 12, respectively; P = 0.02) and in total alkaline phosphatase (1.15 +/- 0.33, 0.83 +/- 0.22, and 0.88 +/- 0.40 mukat/L; P = 0.001). Parameters of bone resorption (urinary hydroxyproline/creatinine ratio, serum acid phosphatase) and the levels of vitamin D metabolites remained unchanged. Serum intact PTH seemed to decrease slightly. Our findings suggest that glucocorticoid induced osteopenia is caused by a depressed bone formation in the presence of an unaltered but ongoing bone resorption. Secondary hyperparathyroidism and changes in vitamin D metabolism are apparently not involved.

Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney

“…Therefore, it is likely that increase in 24-hydroxylase expression by dexamethasone administration does not affect the plasma accumulation of 1,25(OH) 2 D 3 in low and normal vitamin D status. This finding is consonant with the results of clinical studies performed previously (Seeman et al 1980, Prummel et al 1991.…”

“…However, studies attempting to demonstrate such an effect have yielded conflicting results. Chronic glucocorticoid excess has had varied reported effects on plasma 1,25(OH) 2 D 3 concentrations, including increases (Bikle et al 1993, Cosman et al 1994, no change (Seeman et al 1980, Prummel et al 1991, and decreases (Chesney et al 1978, Morris et al 1990). Moreover, whether chronic glucocorticoid excess influences plasma concentrations of 24,25(OH) 2 D 3 is not known.…”

New understanding of glucocorticoid action in bone cells

“…Based on these data, GCs would increase the bone-resorption activity of osteoclasts. However, histomorphometric analysis in patients receiving GC therapy indicated a reduction of both bone resorption and bone formation (2,37,38). On the other hand, treatment with synthetic GCs, dexamethasone suppresses the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts by downregulating β3 integrin, which is essential in the modulation of the cytoskeleton (39).…”

Growth Hormone Cannot Enhance the Recovery of Dexamethasone-Induced Osteopenia after Withdrawal in Young Female Wistar Rats

“…The animal blood was collected after decapiGlucocorticoids (GCs)-induced osteoporosis (GIO) has been shown to be associated with decreased secretion and function of sex steroids (hypogonadism) (Lukert and Raisz 1990;Reid 1997), growth hormone, insulin-like growth factor-I (IGF-I) (McCarthy et al 1990;Bozzola et al 1991;Miell et al 1991;Rydziel and Canalis 1995;Ward et al 1998), and serum osteocalcin (Prummel et al 1991), as well as a suppressed activity and shorter active life span of osteoblasts (Dempster et al 1983). Additionally, GIO may be related to a secondary hyperparathyroidism due to decreased gastrointestinal calcium absorption and increased urinary calcium excretion (Adler and Rosen 1994;Canalis 1996;Reid 1997).…”