Research Paper|Volume 9, Issue 1|pp 256—285

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures

Sifat Maria¹, Mark H. Swanson², Larry T. Enderby³, Frank D’Amico⁴, Brianna Enderby¹, Rebekah M. Samsonraj⁵, Amel Dudakovic⁵, Andre J. van Wijnen⁵, Paula A. Witt-Enderby¹

¹Division of Pharmaceutical Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA 15282, USA
²Functional Medicine, Heart Preventics, LLC, Sequim, WA 98382, USA
³Enderby Healthcare/Legal Consulting, LLC, Pittsburgh, PA 15102, USA
⁴Department of Mathematics, Duquesne University School of Liberal Arts, Pittsburgh, PA 15282, USA
⁵Mayo Clinic, Department of Orthopedic Surgery, Rochester, MN 55905, USA

Received: November 8, 2016Accepted: January 15, 2017Published: January 26, 2017

https://doi.org/10.18632/aging.101158

Copyright: © 2017 Maria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.