Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups

Abstract

Context:Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role.Objective:We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH.Participants:Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country).Interventions:Observational study with sample collection every 4 hours for 24 hours.Main Outcomes:Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH.Results:Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group.Conclusions:Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss.

24-hour profile of serum sclerostin and its association with bone biomarkers in men

“…These data confirm the presence and timing of CTX 24-h rhythmicity but add to the conflicting reports of P1NP rhythmicity [2,14]. The fitted curves for serum P1NP appeared to have a diurnal profile when assessed visually on a magnified scale (Online Resource Fig 1), albeit with a very small amplitude, and when rhythmicity was assessed by the Rao spacing test (Fig 2c polar plot ), which tests whether the individuals’ peak times are clustered.…”

“…However, no significant rhythm was identified with the more robust cosinor analysis. The variability in P1NP relative to an absent or relatively small amplitude rhythm and its long half-life (10 h) may limit the ability to detect a rhythm in these data [14]. …”

“…EDTA plasma) could yield different results. A cosinor model was chosen for this data analysis because the most robust bone biomarker rhythm (CTX) has a visually clear sinusoidal rhythm [1], as do other bone biomarkers [14,6]. Although a more complex rhythm may be present in sclerostin, the approach we used is the most appropriate for investigating the osteocyte-osteoclast rhythm relationship because it is presumed that endogenous rhythms of the bone biomarkers would be similar (i.e.…”

Circadian disruption by shifting the light‐dark cycle negatively affects bone health in mice

“…While osteoclasts degrade and resorb mineralized bone, osteoblasts produce bone matrix which is mineralized to form new bone. 17 Recently, it has been shown that circulating bone turnover markers exhibit a circadian rhythm in humans 18 and are negatively affected by a combination of circadian disruption and sleep restriction. Activation of RANK stimulates osteoclast differentiation, maturation, and activity, thereby increasing bone resorption.…”

MicroRNA and Human Bone Health

“…However, the association was only significant in vertebral fracture but not in other fractures. Moreover, most of the BTMs are subject to diurnal variation . Therefore, research efforts have been diverted to identifying novel blood‐base bone biomarkers.…”