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Relationship between melatonin and bone resorption rhythms in premenopausal women

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Abstract

Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light–dark cycle, and the sleep–wake cycle is difficult to differentiate given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase. Most participants had significant 24-h aMT6s rhythms during both ambulatory and CR conditions (95 and 85%, respectively), but fewer had significant 24-h NTx rhythms (70 and 70%, respectively). Among individuals with significant rhythms, mean (± SD) aMT6s acrophase times were 3:57 ± 1:50 and 3:43 ± 1:25 h under ambulatory and CR conditions, respectively, and 23:44 ± 5:55 and 3:06 ± 5:15 h, respectively, for NTx. Mean 24-h levels of both aMT6s and NTx were significantly higher during CR compared with ambulatory conditions (p < 0.0001 and p = 0.03, respectively). Menstrual phase (follicular versus luteal) had no impact on aMT6s or NTx timing or 24-h levels. This study confirms an endogenous circadian rhythm in NTx with a night-time peak when measured under CR conditions, but also confirms that environmental factors such as the sleep–wake or light–dark cycles, posture or meal timing affects overall concentrations and peak timing under ambulatory conditions, the significance of which remains unclear.

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Acknowledgements

MAStH and SAR were supported by a National Heart, Lung and Blood Institute fellowship in the program of training in Sleep, Circadian and Respiratory Neurobiology at Brigham and Women’s Hospital (T32 HL079010). PWE was supported by the Resident Fellow Translational Research Program in the Division of Clinical, Social and Administrative Sciences at the Duquesne University School of Pharmacy.

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Authors and Affiliations

  1. Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital, 221 Longwood Avenue BLI-438, Boston, MA, 02115, USA

    Melissa A. St Hilaire, Shadab A. Rahman & Steven W. Lockley

  2. Division of Sleep Medicine, Harvard Medical School, 221 Longwood Avenue BLI-438, Boston, MA, 02115, USA

    Melissa A. St Hilaire, Shadab A. Rahman & Steven W. Lockley

  3. Programme in Neuroscience and Behavioural Disorders, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore

    Joshua J. Gooley

  4. Division of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA

    Paula A. Witt-Enderby

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  1. Melissa A. St Hilaire
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  3. Joshua J. Gooley
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Correspondence to Melissa A. St Hilaire.

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Conflict of interest

In the last 24 months, MAStH has provided consulting services to The MathWorks Inc., MentalWorkout, and the Cooperative Research Centre for Alertness, Safety and Productivity, Australia. None of these commercial interests are related to the research or topic reported in this article. SAR, JJG, and PWE report no conflicts of interest. SWL has had a number of commercial interests in the last 24 months. None of them are directly related to the research or topic reported in this article; however, in the interests of full disclosure, are outlined below. In the past 2 years (2014–2016), SWL has received consulting fees from the Atlanta Falcons, Atlanta Hawks, Carbon Limiting Technologies Ltd on behalf of PhotonStar LED, Perceptive Advisors, and Serrado Capital; has current consulting contracts with Akili Interactive, Delos Living LLC, Environmental Light Sciences LLC, Focal Point LLC, Headwaters Inc., Hintsa Performance AG, Light Cognitive, OpTerra Energy Services Inc., Pegasus Capital Advisors LP, PlanLED, and Wyle Integrated Science and Engineering; owns equity in iSleep pty, Australia; has received unrestricted equipment gifts from Bioilluminations LLC, Bionetics Corporation, and F. Lux Software LLC; has received royalties from Oxford University Press; has received honoraria plus travel, accommodation or meals for invited seminars, conference presentations or teaching from Estee Lauder, Informa Exhibitions (USGBC), and Lightfair; travel, accommodation and/or meals only (no honoraria) for invited seminars, conference presentations or teaching from FASEB, Lightfair and USGBC. Through Brigham and Women’s Hospital, SWL has ongoing investigator-initiated research Grants from Biological Illuminations LLC and F. Lux Software LLC; has completed service agreements with Rio Tinto Iron Ore and Vanda Pharmaceuticals Inc; and had completed three sponsor-initiated clinical research contracts with Vanda Pharmaceuticals Inc. SWL holds process patents for the use of short-wavelength light for resetting the human circadian pacemaker and improving alertness and performance, and for a novel method to measure sleep, which are assigned to the Brigham and Women’s Hospital per Hospital policy. SWL has also served as a paid expert in arbitrations related to sleep, circadian rhythms and work hours and legal proceedings related to light, sleep and health. SWL is also a Program Leader for the Cooperative Research Centre for Alertness, Safety and Productivity, Australia.

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St Hilaire, M.A., Rahman, S.A., Gooley, J.J. et al. Relationship between melatonin and bone resorption rhythms in premenopausal women. J Bone Miner Metab 37, 60–71 (2019). https://doi.org/10.1007/s00774-017-0896-6

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