title: Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.
abstract: Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, THG, Aarhus, Denmark.
authors.forename: Anne Kristine
authors.initials: AK
authors.lastname: Amstrup
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, THG, Aarhus, Denmark.
authors.forename: Tanja
authors.initials: T
authors.lastname: Sikjaer
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Heickendorff
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, THG, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, THG, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*
keywords: bone mineral density; clinical trial; melatonin; osteoporosis; postmenopausal women