Melatonin osteoporosis prevention study (MOPS): a randomized, double‐blind, placebo‐controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women

Abstract

The purpose of this double-blind study was to assess the effects of nightly melatonin supplementation on bone health and quality of life in perimenopausal women. A total of 18 women (ages 45-54) were randomized to receive melatonin (3mg, p.o., n=13) or placebo (n=5) nightly for 6months. Bone density was measured by calcaneal ultrasound. Bone turnover marker (osteocalcin, OC for bone formation and NTX for bone resorption) levels were measured bimonthly in serum. Participants completed Menopause-Specific Quality of Life-Intervention (MENQOL) and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after treatment. Subjects also kept daily diaries recording menstrual cycling, well-being, and sleep patterns. The results from this study showed no significant change (6-month-baseline) in bone density, NTX, or OC between groups; however, the ratio of NTX:OC trended downward over time toward a ratio of 1:1 in the melatonin group. Melatonin had no effect on vasomotor, psychosocial, or sexual MENQOL domain scores; however, it did improve physical domain scores compared to placebo (mean change melatonin: -0.6 versus placebo: 0.1, P<0.05). Menstrual cycling was reduced in women taking melatonin (mean cycles melatonin: 4.3 versus placebo: 6.5, P<0.05), and days between cycles were longer (mean days melatonin: 51.2 versus placebo: 24.1, P<0.05). No differences in duration of menses occurred between groups. The overall PSQI score and average number of hours slept were similar between groups. These findings show that melatonin supplementation was well tolerated, improved physical symptoms associated with perimenopause, and may restore imbalances in bone remodeling to prevent bone loss. Further investigation is warranted.

An Early Development Budget Impact Model for the Use of Melatonin in the Treatment and Prevention of Osteoporosi

“…Therefore, the addition of melatonin to a formulary will provide substantial cost offsets to the payer in the treatment and prevention of OP under the assumption that the effectiveness of melatonin is equal to or better than its comparators. Long-term, longitudinal trials comparing melatonin to gold standard treatments are warranted; however recently published clinical studies [17] or yet-to-be-published studies by Dr. Amstrup et al, assessing the efficacy of melatonin to prevent or treat OP show promise with respect to renormalizing serum bone marker status in perimenopausal women [17] and improving bone density in postmenopausal osteopenic women, respectively. Although studies assessing the impact of melatonin on bone health in humans are in their infancy, they are gaining ground.…”

“…These events coincide with the decline in melatonin levels with age implying an association between bone homeostasis and melatonin production. In support of this association, the Melatonin Osteoporosis Prevention Study (MOPS; NCT01152580) revealed that melatonin improved bone health in perimenopausal women by renormalizing bone marker turnover [17]. Previous work also from the Witt-Enderby group has shown a role for MT 2 melatonin receptors in melatonininduced mesenchymal stem cell differentiation into osteoblasts [18,19].…”

Extracellular matrix modulates the biological effects of melatonin in mesenchymal stem cells

“…The beneficial effects of melatonin on bone metabolism have been detected in numerous studies. As a night supplement, melatonin improves bone health and prevents bone loss in perimenopausal women without major side effects (Kotlarczyk et al 2012). In addition, melatonin exerts an osteoinductive effect by promoting osteogenic maturation of human adult MSCs , as well as cartilage matrix synthesis by articular chondrocytes ).…”

Melatonin regulates human bone sialoprotein gene transcription

“…Furthermore, melatonin regulates various physiological and pathophysiological processes such as control of body temperature, sexual development, inflammation, the immune reponse and cell proliferation (8)(9)(10)(11)(12)(13). Melatonin also regulates bone remolding, prevents osteoporosis, and induces dentine formation and osseointegration of dental implants (14)(15)(16)(17)(18).…”