Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients

Objective: Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. Study design: An open cross-over study randomising ten hypopituitary men with severe ACTH deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). Methods: Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP: CTX-I) and as an index using standardised scores derived from the matched controls. Results: There were significant increases in the concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and in the PINP: CTX-I ratio (P=0.015), and a more positive bone remodelling balance index (P=0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. Conclusion: Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.