Bone mineral density and bone turnover changes with advanced menstrual recovery: The REFUEL study

To investigate whether experiencing ≥2 consecutive menstrual cycles of <36 days improved bone mineral density (BMD) and bone turnover markers in response to increased energy intake in young exercising women with oligo-amenorrhea.

The REFUEL study was a 12-month RCT designed to increase energy intake to improve menstrual function and bone health in exercising women with oligo-amenorrhea. Participants from the intervention group were considered recovered (REC; n = 14) if they experienced ≥2 consecutive menstrual cycles of <36 days, and non-recovered otherwise (non-REC; n = 11). DXA scans assessed body composition and BMD at baseline and at the last measurement time point (month 6, 9, or 12). Urinary estrone-1-glucuronide (E1G) and pregnanediol glucuronide were measured daily. Serum insulin-like growth factor-1 (IGF-1), carboxy-terminal telopeptide of type I collagen (CTx), procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin were assessed at baseline and at the last measurement time point (month 3, 6, 9, or 12). Bone balance (BB) was calculated from P1NP, CTx, and osteocalcin ratios relative to a healthy reference population. Linear mixed models assessed changes over time.

Significant group*time effects were observed for lumbar spine BMD (F(1,20.1) = 4.65, p = 0.043), BB calculated from P1NP and CTx (F(1,23) = 5.60, p = 0.027), E1G AUC (F(1,20.7) = 9.86, p = 0.005), and E1G mean (F(1,20.6) =11.84, p = 0.002), indicative of improvements in the REC group compared with non-REC. Significant group effects demonstrated higher IGF-1 in REC than non-REC (F(1,22.9) = 8.43, p = 0.009).

These results indicate that a nutrition intervention can improve bone health when ≥2 consecutive menstrual cycles of <36 days are achieved.