Chronobiology and Chronotherapy of Osteoporosis

Winter, Elizabeth M.; Kooijman, Sander; Appelman‐Dijkstra, Natasha M.; Meijer, Onno C.; Rensen, Patrick C.N.; Schilperoort, Maaike

doi:10.1002/jbm4.10504

Cited by 20 publications

(19 citation statements)

References 147 publications

(187 reference statements)

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“…In the group of untreated patients, a diurnal variation of CTX of 21% per hour was shown. This variation during daytime is well known, ( 13 ) and Quist and colleagues demonstrated a variation in CXT of 15% per hour (80% change from 8 a.m. to 2 p.m.) in both premenopausal women, early and late postmenopausal women, and in men. ( 29 ) Further, we showed in patients using ARD that P1NP and CTX showed no variations during daytime.…”

Section: Discussionmentioning

confidence: 75%

“…This is especially important for measurement of CTX because it is influenced by food intake and exhibits significant diurnal variation. ( 12 , 13 ) Fasting morning sampling is not necessary for measurement of P1NP because of minimal diurnal variation. ( 14 ) In real life, patients often do not attend fasting in the morning as requested, and to estimate variations in BTM during the day is therefore of interest for interpretation of BTM in a clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures

et al. 2022

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The serum bone turnover markers (BTM) procollagen type 1 N‐terminal propeptide (P1NP) and C‐terminal cross‐linking telopeptide of type 1 collagen (CTX) are recommended for monitoring adherence and response of antiresorptive drugs (ARD). BTM are elevated about 1 year after fracture and therefore BTM target values are most convenient in ARD treatment follow‐up of fracture patients. In this prospective cohort study, we explored the cut‐off values of P1NP and CTX showing the best discriminating ability with respect to adherence and treatment effects, reflected in bone mineral density (BMD) changes. Furthermore, we explored the ability of BTM to predict subsequent fractures and BTM variation during daytime in patients using ARD or not. After a fragility fracture, 228 consenting patients (82.2% women) were evaluated for ARD indication and followed for a mean of 4.6 years (SD 0.5 years). BMD was measured at baseline and after 2 years. Serum BTM were measured after 1 or 2 years. The largest area under the curve (AUC) for discrimination of patients taking ARD or not was shown for P1NP <30 μg/L and CTX <0.25 μg/L. AUC for discrimination of patients with >2% gain in BMD (lumbar spine and total hip) was largest at cut‐off values for P1NP <30 μg/L and CTX <0.25 μg/L. Higher P1NP was associated with increased fracture risk in patients using ARD (hazard ratio [HR]logP1NP = 15.0; 95% confidence interval [CI] 2.7–83.3), p = 0.002. P1NP and CTX were stable during daytime, except in those patients not taking ARD, where CTX decreased by 21% per hour during daytime. In conclusion, P1NP <30 μg/L and CTX <0.25 μg/L yield the best discrimination between patients taking and not taking ARD and the best prediction of BMD gains after 2 years. Furthermore, higher P1NP is associated with increased fracture risk in patients on ARD. BTM can be measured at any time during the day in patients on ARD. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures

et al. 2022

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“…Daily GC rhythm should be considered during GC therapy. Chronotherapy when administering GCs could help to increase therapeutic efficacy, and reduce detrimental effects, although further investigations are required considering that the drug half-life and bioavailability can be inflexible ( 93 ). In addition, preclinical models considering factors such as physical stress, aging, and diseases can be introduced to investigate diverse clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

et al. 2022

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Glucocorticoids (GCs) are steroid hormones that respond to stress and the circadian rhythm. Pharmacological GCs are widely used to treat autoimmune and chronic inflammatory diseases despite their adverse effects on bone after long-term therapy. GCs regulate bone homeostasis in a cell-type specific manner, affecting osteoblasts, osteoclasts, and osteocytes. Endogenous physiological and exogenous/excessive GCs act via nuclear receptors, mainly via the GC receptor (GR). Endogenous GCs have anabolic effects on bone mass regulation, while excessive or exogenous GCs can cause detrimental effects on bone. GC-induced osteoporosis (GIO) is a common adverse effect after GC therapy, which increases the risk of fractures. Exogenous GC treatment impairs osteoblastogenesis, survival of the osteoblasts/osteocytes and prolongs the longevity of osteoclasts. Under normal physiological conditions, endogenous GCs are regulated by the circadian rhythm and circadian genes display oscillatory rhythmicity in bone cells. However, exogenous GCs treatment disturbs the circadian rhythm. Recent evidence suggests that the disturbed circadian rhythm by continuous exogenous GCs treatment can in itself hamper bone integrity. GC signaling is also important for fracture healing and rheumatoid arthritis, where crosstalk among several cell types including macrophages and stromal cells is indispensable. This review summarizes the complexity of GC actions via GR in bone cells at cellular and molecular levels, including the effect on circadian rhythmicity, and outlines new therapeutic possibilities for the treatment of their adverse effects.

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“…Several genes that have diurnal patterns, including Clock, Bmal1 , Per1, Per2, Cry1, and Rev-erb-α, are expressed in calvaria and long bones of mice. In vitro , the expression of these genes has also been reported in osteoblasts and osteoclasts [for a recent comprehensive review, refer to Winter et al (2021) ]. Genetic disruption of clock genes affects bone metabolism.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Assessment of the Therapeutic Potential of Melatonin for the Treatment of Osteoporosis Through a Narrative Review of Its Signaling and Preclinical and Clinical Studies

2022

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Melatonin is a bioamine produced primarily in the pineal gland, although peripheral sites, including the gut, may also be its minor source. Melatonin regulates various functions, including circadian rhythm, reproduction, temperature regulation, immune system, cardiovascular system, energy metabolism, and bone metabolism. Studies on cultured bone cells, preclinical disease models of bone loss, and clinical trials suggest favorable modulation of bone metabolism by melatonin. This narrative review gives a comprehensive account of the current understanding of melatonin at the cell/molecular to the systems levels. Melatonin predominantly acts through its cognate receptors, of which melatonin receptor 2 (MT2R) is expressed in mesenchymal stem cells (MSCs), osteoblasts (bone-forming), and osteoclasts (bone-resorbing). Melatonin favors the osteoblastic fate of MSCs, stimulates osteoblast survival and differentiation, and inhibits osteoclastogenic differentiation of hematopoietic stem cells. Produced from osteoblastic cells, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) critically regulate osteoclastogenesis and melatonin by suppressing the osteoclastogenic RANKL, and upregulating the anti-osteoclastogenic OPG exerts a strong anti-resorptive effect. Although the anti-inflammatory role of melatonin favors osteogenic function and antagonizes the osteoclastogenic function with the participation of SIRT signaling, various miRNAs also mediate the effects of the hormone on bone cells. In rodent models of osteoporosis, melatonin has been unequivocally shown to have an anti-osteoporotic effect. Several clinical trials indicate the bone mass conserving effect of melatonin in aging/postmenopausal osteoporosis. This review aims to determine the possibility of melatonin as a novel class of anti-osteoporosis therapy through the critical assessment of the available literature.

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Chronobiology and Chronotherapy of Osteoporosis

Cited by 20 publications

References 147 publications

Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures

Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

Assessment of the Therapeutic Potential of Melatonin for the Treatment of Osteoporosis Through a Narrative Review of Its Signaling and Preclinical and Clinical Studies

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