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Osteoclast resorptive activity, which is known to demonstrate circadian rhythmicity, is regulated by various endocrine hormones and cytokines. PTH suppresses osteoprotegerin (OPG), a regulator of osteoclast activity that has recently been shown to have a circadian rhythm in healthy controls. We studied the differences in the relationship between PT...
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The beneficial effect of obesity on bone mineral density (BMD) has not been definitely established.
The aim of the study was to evaluate changes in BMD in obese perimenopausal women during a 5-year follow-up.
The study involved 54 obese women. The group was divided into 2 subgroups according to the menopausal status: postmenopausal women--M (n = 35...
Citations
... Peripheral venous blood (within 24 h) was collected from elderly men and premenopausal and postmenopausal women every hour, and PTH, OPG, and CTX levels displayed circadian rhythms. The highest OPG levels appeared in the daytime and the lowest appeared at night, while PTH and CTX levels had opposite patterns (Joseph et al., 2007). 20 women (25-65 years old) were studied and serum OC and CTX had the lowest levels during the day, and the highest at night. ...
Osteoporosis is characterized by a high incidence rate, with significant effects on people’s lives. The underlying mechanisms are complex, with no treatments for the condition. Recent studies have indicated that melatonin can be used to treat osteoporosis by promoting osteoblast proliferation and differentiation, and inhibiting osteoclast differentiation. Specifically, in vivo mechanisms are initiated by stabilizing biological rhythms in bone tissue. In healthy organisms, these biological rhythms are present in bone tissue, and are characterized by bone formation during the day, and bone resorption at night. When this rhythm is disrupted, osteoporosis occurs. Thus, taking appropriate medication at different times of the day could produce different effects on osteoporosis rhythms. In this review, we characterized these processes, and provided treatments and management strategies for individuals with osteoporosis.
... Our results show that decreases in PTH-secretion were followed by decreases in CTX level in all participants. This supports a bone resorption effect of PTH on osteoclasts, bone resorptive cells (Joseph et al., 2007;Silva & Bilezikian, 2015). ...
Objectives:
Ethnic groups differ in prevalence of calcium-related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis may play a role. Thus, we aimed to investigate details of CR pattern in calcium and bone homeostasis in East African Maasai.
Methods:
Ten clinically healthy adult Maasai men and women from Tanzania were examined. Blood samples were collected every 2nd hour for 24 h. Serum levels of total calcium, albumin, parathyroid hormone (PTH), 25(OH)D, creatinine, C-terminal telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin were measured. Circadian patterns were derived from graphic curves of medians, and rhythmicity was assessed with Fourier analysis.
Results:
PTH-levels varied over the 24 h exhibiting a bimodal pattern. Nadir level corresponded to 65% of total 24-h mean. CTX and P1NP showed 24-h variations with a morning nadir and nocturnal peak with nadir levels corresponding to 23% and 79% of the 24-h mean, respectively. Albumin-corrected calcium level was held in a narrow range and alterations were corresponding to alterations in PTH. There was no distinct pattern in 24-h variations of 25(OH)D, creatinine, osteocalcin, or BSAP.
Conclusions:
All participants showed pronounced 24-h variations in PTH and bone turnover markers CTX and P1NP. These findings support that Maasai participants included in this study have typical patterns of CR in calcium and bone homeostasis consistent with findings from other ethnic populations.
... One study found a visual but not significant circadian variation of PINP, which was believed to reflect either the absence or small amplitude of circadian changes in PINP [24]. The studies on bone resorption markers CTX and carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) also found a clear circadian rhythm with nighttime or early morning peak which appears to be unaffected by ethnicity [18,19,21,24,25]. For CTX the 24-h MESOR for young participants was 890 ± 100 ng/l with an amplitude of 250 ± 50 ng/l and a nadir at 13.30 [24]. ...
... For CTX the 24-h MESOR for young participants was 890 ± 100 ng/l with an amplitude of 250 ± 50 ng/l and a nadir at 13.30 [24]. There are marked differences in the 24-h mean concentrations of CTX where post-menopausal women had higher levels than elderly men whom again had higher levels than pre-menopausal woman; however, these differences do not affect the circadian rhythmicity [25]. For PTH, involved in calcium metabolism and a promotor of bone resorption, there exists a biphasic circadian rhythm with two peaks, one early morning and one late evening [26][27][28]; however, interestingly the circadian rhythm of PTH is not a mediator of the circadian rhythm of other BM [29]. ...
... For PTH, involved in calcium metabolism and a promotor of bone resorption, there exists a biphasic circadian rhythm with two peaks, one early morning and one late evening [26][27][28]; however, interestingly the circadian rhythm of PTH is not a mediator of the circadian rhythm of other BM [29]. There appeared to be no effect of ethnicity on the circadian rhythm of PTH but a clear effect of age, with elderly men and postmenopausal women having the highest MESOR of 5.38 ± 0.1 pmol/l and 5.83 ± 0.06 pmol/l, respectively [20,25,30]. Likewise, was there a sex difference with men having an earlier and greater increase at night than women [31]. ...
There exists a marked circadian variation for several bone markers (BM), which is influenced by endogenous as well as exogenous factors including hormones, physical activity, and fasting. Consequently, was the aim of this review to provide an overview of the knowledge of the circadian variation of BM and which factors influence this rhythmicity. A systematic search of PubMed was performed for studies evaluating the circadian variation of BM and which factors influence this rhythmicity. The studies were screened for eligibility by a set of predetermined criteria including a list of relevant BM and a minimum study duration of 24 h with at least 3 blood samples of which two should be at least 6 h apart. In total were 29 papers included. There exists a marked circadian variation for most BM including Carboxy-terminal Cross-Linked Telopeptide of Type I Collagen (CTX) and osteocalcin (OC) with nighttime or early morning peak. Pro-collagen Type I N-terminal Propeptide (PINP) and PTH also showed circadian rhythm but with less amplitude. The inter-osteoblast-osteoclast regulatory markers such as OPG, RANKL, FGF23, and sclerostin showed no circadian rhythm. The markers were differently affected by exogenous factors like fasting, which greatly reduced the circadian variation of CTX but did not affect PINP or OC. The marked circadian variation and the factors which influence the rhythmicity, e.g., fasting are of great consequence when measuring BM. To reduce variation and heighten validity should circadian variation and fasting be kept in mind when measuring BM.
... There have been studies in the last few decades that suggest that circulating PTH levels vary throughout a 24-h period and do so in a circadian manner. These changes in circulating levels of PTH in those studies were consistently at a maximum of about 30% and within the normal circulation range of 2 to 6 pmol/L (211)(212)(213). By contrast, persistent elevation of circulating PTH resulting from primary hyperparathyroidism, from prolonged PTH treatment, or from transgenic overexpression of PTH1R in mice, results in a generalized activation of remodeling sites and therefore increased resorption. ...
The hormone, parathyroid hormone (PTH) and the paracrine factor, parathyroid hormone-related protein (PTHrP) have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein coupled receptor, PTH1R, that predominantly uses the cyclic AMP (cAMP)-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies shown that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling. In contrast, the main postnatal function of PTH is hormonal control of calcium homeostasis, with no evidence that PTHrP contributes. Pharmacologically, amino-terminal PTH and PTHrP peptides (teriparatide and abaloparatide) promote bone formation when administered by intermittent (daily) injection. This anabolic effect is remodeling-based with a lesser contribution from modeling. The apparent lesser potency of PTHrP than PTH peptides as skeletal anabolic agents could be explained by lesser bioavailability to PTH1R. By contrast, prolongation of PTH1R stimulation by excessive dosing or infusion, converts the response to a predominantly resorptive one by stimulating osteoclast formation. Physiologically, locally generated PTHrP is better equipped than the circulating hormone to regulate bone remodeling, which occurs asynchronously at widely distributed sites throughout the skeleton where it is needed to replace old or damaged bone. While it remains possible that PTH, circulating within a narrow concentration range, could contribute in some way to remodeling and modeling, its main physiological role is in regulating calcium homeostasis.
... There have been studies that suggest that circulating PTH levels vary in a circadian manner in human subjects. The changes in circulating levels of PTH in those studies were consistently at a maximum of about 40% and within the normal circulation range of 2e6 pmol/L (Fraser et al., 1998;Rejnmark et al., 2002;Joseph et al., 2007). In one such study (Logue et al., 1989) the late night/early morning increase in plasma PTH rose in parallel with nephrogenous cAMP, suggesting the change in PTH may be sufficient to produce an appropriate response in the kidney target. ...
... A network of channels that represent the lacunar canaliculy system is influenced by osteocytes embedded in bones and variations are measured at micron scale (Gardinier et al. 2018). Long-term manipulation of PTH secretion alters bone cell function, resorption and remodelling (Schlemmer and Hassager 1999;Fraser et al. 2004;Joseph et al. 2007). It is possible that variations of PTH within the normal range affect bone composition. ...
Although the effect of isolated nutrients on plasma parathyroid hormone (PTH) is somewhat familiar, the effect of multiple nutrients on plasma PTH level has not yet been studied. The aim of this study was to identify groups of food items that are associated with the plasma PTH level in healthy individuals.
This cross-sectional study enrolled 1180 healthy individuals from Croatia with plasma PTH levels inside the referent values. A food frequency questionnaire containing 58 food items was completed to evaluate the dietary intake. We used principal component analysis to reduce food items into dietary groups, followed by linear regression analysis to test the association between dietary groups and the level of PTH.
The results indicate that different sorts of vegetables (p = .006), sausages, salami, mushrooms, eggs (p = .033), as well as white bread (p = .009) are associated with the increase, while bran bread (p = .009) is associated with the decreased plasma PTH level.
... Moreover, the expression of osteoprotegerin (OPG), a protein involved in bone remodeling, which acts as an inhibitor of RANK-RANKL signal- ing, was found to be regulated by two clock genes: REV-ERBα and BMAL1, in osteoblastic cells MC3T3-E1 ( Hirai et al. 2015). The circadian rhythm of osteoprotegerin has been also reported in humans ( Joseph et al. 2007). Furthermore, BMAL1 plays an important role in bone homeosta- sis through controlling the mesenchymal stem cells differentiation to mature osteoblasts in vitro. ...
Osteoporosis is an important public health problem worldwide. Among the countries with a very high population risk of fractures, there are those with the highest level of economic development. Osteoporotic fractures are the main cause of disability among elderly people, and the resultant disabilities require particularly large financial support associated not only with the direct treatment of the fracture but also with the necessity for long-term rehabilitation and care for the disabled person. Many well-established factors can have impact on bone mass and fracture risk. Recently, it has been hypothesized that working during nighttime which leads to endocrine disorders may have an indirect impact on bone physiology among night shift workers. Therefore, it can be presumed that the night shift work may contribute to the etiology of osteoporosis. The aim of our work was to make a review of the epidemiological evidence on the association between night shift work and bone mineral density or fracture risk as well as to discuss the potential biological mechanisms linking the work under this system with the development of osteoporosis. We have identified only four studies investigating the association between system of work and bone mineral density or fracture risk among workers. The findings of three out of four studies support the hypothesis. None of the studies has investigated a potential relationship between night shift work and bone turnover markers. Given that there have been no epidemiological studies in European countries that would concern working populations and the noticeable difference in the risk of osteoporosis between communities, further studies are warranted to elucidate the problem. It is presumed that further in-depth studies will not only identify the underlying factors of the disease but also contribute to developing guidelines for policy makers and employers for primary prevention of osteoporosis in workplace.
... CTX is released into the blood circulation when bone collagen is broken down by cleavage of the cross-linked type I collagen by cathepsin K, which is expressed by osteoclasts [1,2]. Serum CTX demonstrates a circadian rhythm with its nadir in the late afternoon and its peak in the second half of the night in healthy individuals [3][4][5][6]. The circadian rhythms of the two key biomarkers of bone formation, osteocalcin and N-terminal propeptide of type 1 procollagen (P1NP), have been investigated in several studies. ...
... The circadian rhythm of CTX with its peak around 05:21 and 05:59 for men and women respectively was similar to that observed in other studies [3][4][5][6]18]. We observed a difference between older men and women in the amplitude of CTX over 24 h, with a larger amplitude in women than in men. ...
The process of bone turnover displays variations over 24 h, with C-terminal cross-linked telopeptide of type 1 collagen (CTX) and osteocalcin exhibiting a nadir in the afternoon and a peak in the night. In contrast, N-terminal propeptide of type 1 procollagen (P1NP) did not display an apparent 24-hour rhythm. Other emerging novel biomarkers of bone, sclerostin and Dickkopf-related protein 1 (DKK1), are markers of osteocyte activity with limited data available regarding their 24-hour profiles. In this study, we aimed to extend available data on 24-hour profiles of CTX, osteocalcin, and P1NP and to assess the 24-hour profiles of sclerostin and DKK1 in healthy older men and women and to compare these between men and women. We measured these five bone markers in EDTA plasma collected every 4 h during 24 h in 37 healthy older men and women (range 52-76 years). Differences between time points were determined using repeated measures ANOVA and cosinor analyses were performed to determine circadian rhythmicity. The circadian rhythm of CTX was confirmed by the cosinor model, with women showing larger amplitude compared to men. Osteocalcin showed higher levels during night-time compared to daytime in both men and women. For P1NP levels we observed a small but significant increase in the night in men. Sclerostin and DKK1 did not show a circadian rhythm, but sclerostin levels differed between time points. Because of the large intraindividual variation, DKK1 as measured in this study cannot be considered a reliable marker for diagnostic or research purposes. In conclusion, when measuring CTX, osteocalcin, P1NP, or sclerostin either in clinical practice or in a research setting, one should consider the 24-hour profiles of these bone markers.
... Further, no rhythmic variations were observed in osteoprotegerin (OPG) or soluble RANKL (sRANKL) serum levels with a diurnal cycle [22,23]. Paradoxically, another study showed that OPG displayed a circadian rhythm of a daytime increase and nocturnal decrease [24]. ...
Numerous physiological processes of mammals, including bone metabolism, are regulated by the circadian clock system, which consists of a central regulator, the suprachiasmatic nucleus (SCN), and the peripheral oscillators of the BMAL1/CLOCK-PERs/CRYs system. Various bone turnover markers and bone metabolism-regulating hormones such as melatonin and parathyroid hormone (PTH) display diurnal rhythmicity. According to previous research, disruption of the circadian clock due to shift work, sleep restriction, or clock gene knockout is associated with osteoporosis or other abnormal bone metabolism, showing the importance of the circadian clock system for maintaining homeostasis of bone metabolism. Moreover, common causes of osteoporosis, including postmenopausal status and aging, are associated with changes in the circadian clock. In our previous research, we found that agonism of the circadian regulators REV-ERBs inhibits osteoclast differentiation and ameliorates ovariectomy-induced bone loss in mice, suggesting that clock genes may be promising intervention targets for abnormal bone metabolism. Moreover, osteoporosis interventions at different time points can provide varying degrees of bone protection, showing the importance of accounting for circadian rhythms for optimal curative effects in clinical treatment of osteoporosis. In this review, we summarize current knowledge about circadian rhythms and bone metabolism.
... Although cyclic progesterone may be appropriate therapy, in every situation a woman needs to be holistically assessed for the other important general and bone health variables such as overall nutrition 43 , body mass index (BMI, kg/m 2 ), adequacy of energy intake for energy expenditure 44 , protein 45 , calcium and vitamin D 46 intakes, sedentary behavior 47 or physical activity 9 , adequacy of sleep and circadian rhythm 48 , and the psychosocial environment to rule out stress, threat, abuse, depression 49 and cognitive dietary restraint 21 (Figure 4). This section will discuss life phases before menopause during which cyclic progesterone may prevent osteoporosis. ...
Estradiol (E2) is women’s dominant ‘bone hormone’ since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent the rapid (3-week) bone resorption that causes most adult BMD loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone (P4) is E2’s physiological partner, collaborating with E2 in every cell/tissue; its bone ‘job’ is to increase P4-receptor-mediated, slow (3–4 months) osteoblastic new bone formation. When menstrual cycles are normal length and normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically normal cycles commonly have ovulatory disturbances (anovulation, short luteal phases) and low P4 levels; these are more frequent in teen and perimenopausal women and increased by everyday stressors: energy insufficiency, emotional/social/economic threats and illness. Meta-analysis shows that almost 1%/year spinal BMD loss occurs in those with greater than median (∼31%) of ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures requires the reversal of stressors, detection and treatment of teen-to-perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized progesterone. Low ‘Peak Perimenopausal BMD’ is likely the primary risk for fragility fractures in later life. Progesterone plus estradiol or other antiresorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. Randomized controlled trials are still needed to confirm progesterone’s important role in women’s bone formation.
