Background: Glucocorticoids reduce bone turnover, and are associated with an increased fracture risk. Recent studies reported insulin can reduce bone resorption and formation1. The aim was to investigate whether hyperinsulinaemia contributes to low bone turnover during glucocorticoid treatment.
Methods: We measured serum osteocalcin and collagen type 1 cross-linked C-terminal telopeptide (CTx) as markers of bone formation and resorption respectively. In study 1, bone turnover was measured fasting and at the end of steady state of a hyperinsulinaemic-euglycaemic clamp (80 mU/m2/min) in 9 subjects with inflammatory arthritis before and after prednisolone 6 mg/day for 7-10 days. In study 2, bone turnover was measured fasting and two hours after a mixed meal in 12 subjects with inflammatory arthritis before and after prednisolone 6 mg/day for 7 days.
Results: In study 1 there were no significant changes in fasting (15±2 vs 17±2 µU/mL, p=0.25) or hyperinsulinaemic (286±15 vs 285±19 µU/mL, p=0.88) insulin after prednisolone. There were no significant changes in bone turnover during hyperinsulinaemic-euglycaemic clamp before (Δ osteocalcin -0.8±0.4 ng/mL, p=0.09; Δ CTx +14±12 ng/mL, p=0.28) or after (Δ osteocalcin -0.3±1.3 ng/mL, p=0.81; Δ CTx +17±25 ng/mL, p=0.52) prednisolone. In study 2 fasting osteocalcin (16.7±1.6 vs 13.6±0.8 ng/mL, p=0.005) fell, with no significant change in fasting insulin (23±5 vs 27±3 µU/mL, p=0.38) or CTx (366±56 vs 373±61 ng/mL, p=0.64). After the meal there was an increase in insulin (p=0.001) and reduction in CTx (p=0.001) that were not affected by prednisolone (p>0.20 for both analyses). After the meal there was an increase in osteocalcin (p<0.001) that was attenuated by prednisolone (p=0.01).
Conclusion: Prednisolone, but not hyperinsulinaemia, reduced the bone formation marker osteocalcin. Consequently reducing hyperinsulinaemia by increasing insulin sensitivity is unlikely to increase osteocalcin or other markers of bone turnover and may not alter fracture risk in patients prescribed glucocorticoids.