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

Abstract

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 (PZ0.045) and OC(1-49) (PZ0.006) and in the PINP:CTX-I ratio (PZ0.015), and a more positive bone remodelling balance index (PZ0.03) 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 (rZK0.66 and PZ0.04) and TRACP5b (rZK0.74 and PZ0.01) in patients on dose B and with OC(1-49) (rZK0.66 and PZ0.04) and CTX-I (rZK0.81 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.

Postoperative changes in bone metabolism and bone mineral density in Japanese patients with acromegaly: a 3-year prospective study

“…Further, in the current study, BAP/urinary NTx ratio was significantly increased at 3 months and 3 years after TSS. Previous studies have reported that the ratio of procollagen type I N-propeptide (PINP) and C-terminal cross-linking telopeptide (CTX-I), other bone turnover markers, reflects the bone remodeling balance [8]. The increase of BAP/urinary NTx ratio after TSS in acromegalic patients suggests that bone formation is superior to bone resorption.…”

Low-dose hydrocortisone replacement is associated with improved arterial stiffness index and blood pressure dynamics in severely adrenocorticotrophin-deficient hypopituitary male patients

“…During the admission, subjects took the predesignated HC dose at 0800, 1600 and 0800 h the following morning of the admission. All patients had a 24-h serum cortisol measurements on treatment as described previously (19,20). Ten healthy-matched controls underwent identical biochemical profiling to the patient group.…”

“…No patient had known diabetes mellitus (DM), two patients had controlled hypertension and were on stable doses of angiotensin-converting enzyme inhibitor medication that was not changed during the study. This patient population has been described in detail in prior publications from our group (19,20). Exclusion criteria were as described in previous publications (19,20), and with particular reference to this analysis, those with uncontrolled hypertension or a known diagnosis of DM were excluded.…”

“…This patient population has been described in detail in prior publications from our group (19,20). Exclusion criteria were as described in previous publications (19,20), and with particular reference to this analysis, those with uncontrolled hypertension or a known diagnosis of DM were excluded. Female patients were excluded because of the variable effects of oestrogen status on a number of parameters that were being assessed in the overall study (21), and also on corticosteroid-binding globulin levels, thus affecting total cortisol concentrations and cortisol kinetics (22).…”

Group 4: Replacement therapy for adrenal insufficiency

“…Conversely, a recent German study on 57 patients showed a variation of 8-10 mg in the daily dose of hydrocortisone over 2 years had a significant impact on bone mineral density [19]. Behan et al showed, in an open crossover study looking at markers of bone turnover and three different doses of hydrocortisone (20-10/10-10/10-5 mg/day), that the weakest dose was associated with an increase in bone formation [20].…”