Effects of Low-Dose Prednisone on Bone Metabolism

Abstract

Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebocontrolled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength.Introduction: High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses >7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects. Materials and Methods: A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD). Results and Conclusions: Prednisone rapidly and significantly decreased serum PINP (p < 0.01), PICP (p < 0.01), and osteocalcin (p < 0.01) and free urinary deoxypyridinoline (p ‫ס‬ 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk.

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

“…In humans, it occurs in two phases: a rapid, early phase in which bone mineral density is reduced possibly due to increased bone resorption, and a slower, progressive phase in which bone mineral density decreases due to impaired bone formation [9]. However, low-dose prednisone was reported to decrease bone formation markers and to decrease the bone resorption marker free urinary deoxypyridinoline in postmenopausal women, indicating the possibility of inhibition of bone resorption [38].…”

Bone turnover and metabolism in paediatric patients with inflammatory bowel disease treated with systemic glucocorticoids

“…In literature, the reported effects of glucocorticoids on bone resorption are inconsistent. Some authors have shown glucocorticoid-induced inhibition of bone resorption in vitro and no change or a downward trend in the markers of bone resorption in vivo (30,31). Others have reported prolonged survival of osteoclasts and increased expression of osteoclastogenesis-promoting agents in response to glucocorticoids (32,33).…”

Clinical application of biochemical markers of bone turnover

“…Together with the fact that high bone turnover may be sustained for long periods and bone loss may increase with age (44), these findings may provide a rationale for designing more effective intervention strategies. However, other factors such as age (see above), medication (6,18,(46)(47)(48)(49)(50)(51), immobilisation (32,35), thyroid function (52), co-morbidity (35) and the fracture itself (40,53,54) do influence bone metabolism and therefore need to be considered in the interpretation of biochemical data and their use in individual patients. Clearly, none of the biochemical markers of bone turnover has proven useful as a single diagnostic index of osteoporosis.…”

“…For example, markers of bone turnover may reflect changes in bone metabolism induced by oophorectomy (57,125), hyperparathyroidism (126,127), Paget's disease (128), physical exercise (129), immobilisation (32,130), alcoholism (131), smoking (132), vitamin D deficiency (33,35,37,133), chronic inflammatory bowel disease (134,135), chronic starvation (136), thyroid disorders (52,137) as well as the pharmacological effects of glucocorticosteroids (48,139,140), androgens (6,7,141), gonadotropin-releasing hormone agonists (142), warfarin (143), growth hormone or insulin-like growth factors (144). Bone turnover markers may be useful in the diagnosis and management of certain of the above conditions, but in most cases has not been rigorously examined.…”