The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis

Abstract

Background: We hypothesized that with the administration of teriparatide (TPTD) treatment at different times, we would be able to modify the physiological circadian rhythm of bone turnover. Methods: The concentration of serum C-terminal telopeptide of collagen type I (bCTX), serum N-terminal propeptide of procollagen type I (P1NP), serum ionized calcium (iCa), and plasma PTH were measured every 3 h over a 24 h period in 14 postmenopausal osteoporotic women (aged 72.4 G9.3 years) treated with 20 mg TPTD for long term, given at different times of the day. General linear model-repeated measurements (GLM RM) were performed to analyze the circadian rhythms as well as intergroup comparisons. Results: GLM-RM for both related groups showed a significant influence of time of day on all measured variables except P1NP. The analysis for each group separately provided a powerful model for bCTX (P!0.001, h 2 Z0.496), serum iCa (P!0.001, h

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.…”

“…Osteoblasts and osteoclasts display daily patterns with circulating markers of bone resorption and, to a lesser extent, bone formation (i.e., osteocalcin), peaking in the early morning with a nadir in the late afternoon [1,2]. Daily patterns are likely important for normal bone remodeling, but may differ between bone cells.…”

Diurnal variability of total calcium during normal sleep and after an acute shift of sleep

“…This limitation is also true for many previous studies with uneven distributions between sexes or only one gender studied (11,12,14,15) . However, Greenspan et al (33) noted no gender differences for serum calcium rhythms in men and women over 65 years of age.…”

“…One of these could be the sampling time if there is a diurnal variation. Both PTH and 1,25-dihydroxyvitamin D has been shown to have a diurnal variation (11,12) . As these hormones are the main regulators of extracellular calcium it seems likely that also calcium could exhibit a diurnal variability.…”

A fluorescence spotlight on the clockwork development and metabolism of bone

“…In particular, the time of day when patients receive their doses of medicine may change its effects on bone metabolism, because of the presence of the innate circadian rhythms in the functions in bone and other related organs. In fact, a recent clinical study demonstrated that administration of teriparatide (a recombinant human PTH1-34) at different times significantly affected the 24-h variation in bone turnover markers, as well as the calcium-parathyroid axis in postmenopausal osteoporotic female patients [137].…”