Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P < 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R' = 0.72, P < 0.001) between serum BGP'" and prednisone dosage, dosage', serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day.Osteoporosis is a serious complication of glucocorticoid therapy. During treatment, bone loss occurs principally in regions of the skeleton that have a high content of cancellous bone, such as the ribs and vertebrae, and this may result in fractures at these sites (1). In a prospective study of glucocorticoidtreated asthmatic patients, the incidence of vertebral or rib fractures was 45% (2). Based on measurements made at the distal radius by single-photon absorptiometry, the prevalence of osteopenia among steroidtreated patients attending rheumatology clinics was 38% (3).Microradiography of rib (4) and histomorphometric analysis of iliac crest bone ( 5 ) from patients with excess levels of glucocorticoids have demonstrated both increased bone resorption and decreased bone formation. Increased bone resorption has been attributed to secondary hyperparathyroidism resulting from glucocorticoid inhibition of gastrointestinal calcium absorption (6-8) and increased urinary calcium loss (9). Other investigators (10,l I) have been unable to find an increase in serum immunoreactive parathyroid hormone (iPTH) and postulate that there may be increased bone sensitivity to iPTH. However, inhibition of bone formation appears to be due to a direct effect of steroids on osteoblast function. Evidence supporting a direct effect of corticosteroids on bone synthesis includes decreased collagen synthesis (12-14), decreased alkaline phosphatase activity (14), decreased production of bone Gla-protein (BGP, or osteocalcin) (IS), and decreased incorporation of 3H-thymidine into DNA and of 3H-uridine into RNA (12,13) by bone cells in vitro, after treatment with glucocorticoids.Bone formation can be assessed indirectly by measurement of serum BGP levels. BGP, the most abundant of the noncollagenous bone proteins, is synthesized by osteoblasts (16,17). Circulating BGP levels have been shown to reflect bone formation, but not resorption, as determined by histomorphometric techniques, in patients with postmenopausal osteoporosis (18), primary hyperparathyroidism, or hyper-