Relationship Between Urinary 6-Sulfatoxymelatonin Rhythms and the Bone Resorption Marker Amino-Terminal Cross-Linked Telopeptide of Collagen I in Blind Women

Abstract

Evidence exists for the daily rhythmicity of bone metabolism that may be influenced by melatonin production, reproductive hormones, the light/dark cycle, or all three, but the ability to determine their independent contributions is confounded by the synchrony of the sleep/wake and dark/light cycles with the endogenous circadian system in sighted individuals. Blind participants, who often have no circadian light perception and may exhibit desynchrony between their sleep/wake cycle and circadian system, provide an opportunity to study the independent contribution of melatonin and light on bone metabolism in a field-based setting. In this exploratory study, 35 pre-, peri-, and postmenopausal blind women (N = 13, 8, and 14, respectively) both with (N = 17) and without (N = 18) visual light perception (LP and NPL, respectively) who were either normally entrained (N = 19) or abnormally entrained or non-entrained (N = 16) to the 24-h day were randomly selected from a cohort of 130 visually impaired women. Levels of 6-sulfatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked telopeptide of collagen I (NTx; BCE nM/h) were assayed from serial urine samples collected over 48 h and fit by a cosinor model to determine the presence of significant 24-h rhythms. Most blind women (N = 32/35, 91%) had a significant 24-h aMT6s rhythm (mean ± SD, 03:44 ± 4:27 hh:mm), but fewer women had a significant 24-h NTx rhythm (N = 20/35, 57%; 21:01 ± 5:50 hh:mm). There was no significant difference in the proportion of women with significant NTx rhythms by visual light perception status (LP: N = 10/17, 59% vs. NPL, N = 10/18, 56%), entrainment status (Entrained: N = 11/19, 58% vs. Abnormal or Not entrained: N = 9/16, 56%) or reproductive status (Premenopausal: N = 7/13, 54% vs. Perimenopausal: 5/8, 63% vs. Postmenopausal: 8/14, 57%). There was no correlation between the peak timings of aMT6s and NTx among the 17 participants with significant rhythms in both metabolites (r = 0.07, p = 0.80). NTx area under the curve was significantly higher among perimenopausal women with LP (p = 0.04). Our results do not support a direct influence of light, melatonin, or reproductive status on NTx rhythms, but the apparent increase of NTx in the perimenopausal period warrants further investigation.