Pilot Study Assessing the Efficacy of Melatonin and Osteogenic Loading on Bone Health in a Postmenopausal Population with Osteopenia: MelaOstrong Randomized Controlled Trial

The purpose of this 1-year study was to assess the effect of osteogenic loading combined with melatonin on musculoskeletal health and well-being in a population with osteopenia. Participants were randomized into one of four groups and received mock loading plus plant fiber as placebo (ML/Placebo), mock loading plus 5 mg melatonin (ML/Melatonin), osteogenic loading plus placebo (OL/Placebo), and osteogenic loading plus 5 mg melatonin (OL/Melatonin). The loading protocol was designed to deliver multiples of body weight (MOB; 1-2 MOB for mock loading and 1.5-4.2 MOB for osteogenic loading) to the upper body (targeting the arm, chest, and shoulders), core (targeting the spine and core stability), lower body (targeting the legs and hip) and postural (targeting the spine and posture). Following these interventions, musculoskeletal health was measured by DXA and functional testing using timed-up-and-go (TUG) and sit-to-stand (STS) assessments. Markers of bone health (e.g., P1NP, CTX, CRP, cortisol, and melatonin) were assessed in urine collected during the night (10 pm-6 am). Mental health assessments were conducted using PSS, CES-D, STAI and QualiOst. Time-dependent increases in the amount of force exerted (in lbs) were observed in the OL groups for all musculoskeletal systems targeted, compared to those participants receiving ML. Over 12mos, compared to baseline, participants in the OL/Melatonin group had statistically significant increases in lumbar spine T-scores (mean difference [MD] = 0.13, standard deviation [SD] = 0.05, p = 0.015) and BMD (MD = 0.013, SD = 0.006, p = 0.021). No other statistically significant effects were noted for T-scores, BMD, or FRAX scores. Additionally, no significant differences were observed when T-scores were compared between groups. Functional assessments at 12mos revealed increases in TUG times (MD = -1.7, SD = 0.3, p = 0.002) from baseline and deterioration for STS (MD = 2.8, SD = 0.59, p = 0.004) from month 03 for ML/placebo group, which did not occur for the other interventions. Correlation analysis revealed negative associations between TUG performance and CTX levels starting at 3mos in the OL/Melatonin group (r = -0.960, p = 0.04). The change in STS repetitions over a 12-month period (12mo-0mo) was negatively associated with the P1NP:CTX ratio (r = -0.978, p = 0.02) and positively associated with melatonin levels in the OL/Melatonin group (r = 0.958, p = 0.04). No changes in nocturnal output of CRP or cortisol and subject-reported outcomes were observed for any of the interventions within and between groups. The results from this study reveal that osteogenic loading combined with melatonin may be an alternative therapeutic intervention for those with osteopenia.