@article{40a6d34bdabf4623a2802d1b5284190e,
title = "24-hour profile of serum sclerostin and its association with bone biomarkers in men",
abstract = "Summary: The osteocyte{\textquoteright}s role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. Introduction: The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. Methods: Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20–65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. Results: No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30–07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30–11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). Conclusions: Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.",
keywords = "Bone remodeling, Bone turnover, Circadian rhythm, Diurnal rhythm, Osteocyte, Sclerostin",
author = "C. Swanson and Shea, {S. A.} and P. Wolfe and S. Markwardt and Cain, {S. W.} and M. Munch and Czeisler, {C. A.} and Orwoll, {E. S.} and Buxton, {O. M.}",
note = "Funding Information: Complimentary graphic design consultation for figures was provided by Brian D. Swanson. Assistance with acquisition of study documentation was provided by Nina Vujovic. Research reported in this manuscript was supported by?grants from the Medical Research Foundation of Oregon Early Clinical Investigator Grant MRF515 and the National Center for Advancing Translational Sciences?of the National Institutes of Health under award number UL1TR000128. Research reported in this publication was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23 AR070275) and the National Institute on Aging (P01 AG009975). The studies were carried out in the Intensive Physiological Monitoring Unit of the Brigham and Women?s Hospital Center for Clinical Investigation, part of the Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciencies (UL1 TR0001102 and UL1 RR025758) and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this manuscript was supported by National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. Funding Information: Research reported in this manuscript was supported by grants from the Medical Research Foundation of Oregon Early Clinical Investigator Grant MRF515 and the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. Research reported in this publication was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23 AR070275) and the National Institute on Aging (P01 AG009975). The studies were carried out in the Intensive Physiological Monitoring Unit of the Brigham and Women{\textquoteright}s Hospital Center for Clinical Investigation, part of the Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciencies (UL1 TR0001102 and UL1 RR025758) and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: S.A.S. received support from NASA grant NNX1OAR1OG, CDC grant U19 OH010154, and NIH grant R01 HL125893. P.W., S.W.C., and M.M. have no disclosures. Funding Information: O.M.B. previously served as consultant to Takeda Pharmaceuticals North America (speaker{\textquoteright}s bureau), Dinsmore LLC (expert witness testimony), Matsutani America (scientific advisory board), and Chevron (speaking fees). Outside of the submitted work, investigator-initiated research grant support from Sepracor (now Sunovion) and Cephalon (now Teva). This work was supported by grants from the National Institute on Aging (NIA) (P01 AG009975) and was conducted in the Brigham and Women{\textquoteright}s Hospital General Clinical Research Center supported by the National Center for Research Resources (NCRR) (M01 RR02635), the CCI of the Harvard Clinical and Translational Science Center (1 UL1 RR025758-01), and with support from the Joslin Diabetes and Endocrinology Research Center Service (5P30 DK 36836) Specialized Assay Core. O.M.B. was supported in part by the NHLBI (R01HL107240). Funding Information: Research reported in this manuscript was supported by National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. Funding Information: E.S.O. for The Osteoporotic Fractures in Men (MrOS) Study, and the National Institutes of Health via the following institutes: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research, under the following grant numbers: U01AG027810, U01 AG042124, U01 AG042139, U01 AG042140,U01 AG042143, U01 AG042145, U01 AG042168, U01AR066160, and UL1 TR000128. Funding Information: S.M. received support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1TR000128 from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). Funding Information: C.M.S. received support from NIH grant T32 DK007674, NIH grant T32 DK007446, K23 AR070275, and the Medical Research Foundation of Oregon Early Clinical Investigator Grant MRF515. Publisher Copyright: {\textcopyright} 2017, International Osteoporosis Foundation and National Osteoporosis Foundation.",
year = "2017",
month = nov,
day = "1",
doi = "10.1007/s00198-017-4162-5",
language = "English (US)",
volume = "28",
pages = "3205--3213",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",
number = "11",
}