Quantitative differences in binding of a fluorescent bisphosphonate to bone minerals are observed in mouse models of bone turnover: potential for application as an imaging probe for bone metabolism

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

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Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-1183 ◽

2016 ◽

Vol 101 (8) ◽

pp. 3222-3230 ◽

Cited By ~ 25

Author(s):

Jean Redmond ◽

Anthony J. Fulford ◽

Landing Jarjou ◽

Bo Zhou ◽

Ann Prentice ◽

...

Keyword(s):

Bone Turnover ◽

Bone Metabolism ◽

Ethnic Groups ◽

Bone Turnover Markers ◽

Type I Collagen ◽

Diurnal Rhythms ◽

Type I ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Turnover Markers

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.

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Bone Metabolism, Bone Mineral Content, and Density in Elite Late Teen Female Sprinters

International Journal of Sports Medicine ◽

10.1055/a-1432-2587 ◽

2021 ◽

Author(s):

Yuka Tsukahara ◽

Suguru Torii ◽

Fumihiro Yamasawa ◽

Jun Iwamoto ◽

Takanobu Otsuka ◽

...

Keyword(s):

Bone Turnover ◽

Bone Mineral Content ◽

Bone Metabolism ◽

Bone Mineral ◽

Bone Turnover Markers ◽

Mineral Content ◽

Whole Body ◽

Tartrate Resistant Acid Phosphatase ◽

Intensive Training ◽

Turnover Markers

AbstractWith intensive training, bone injuries are a major concern for athletes. To assess bone condition, we often measure bone turnover markers, bone mineral content and density; however, in junior athletes, it is not easy to distinguish changes caused by bone injuries from those caused by growth, because the metabolism is increased in both cases. Moreover, although some studies have examined female endurance athletes, knowledge regarding changes in static and dynamic bone conditions in late teen athletes is limited. In this study, we measured the bone mineral content and density, as well as bone turnover markers, in 40 elite female sprinters in their late teens. Whole body mode dual-energy X-ray absorptiometry was performed to measure bone mineral content and density. Blood samples were collected to determine bone resorption and formation markers at the end of track season in 2016 and during the same period of the following year. Body weight and bone mineral content significantly increased, and tartrate-resistant acid phosphatase type 5b, bone-type alkaline phosphatase, and osteocalcin significantly decreased after a year. Furthermore, the rate of change in bone mineral content was higher in younger athletes, indicating that bone growth approaches completion in the late teen years and that bone metabolism accordingly decreases.

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A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models

Antioxidants ◽

10.3390/antiox8090386 ◽

2019 ◽

Vol 8 (9) ◽

pp. 386 ◽

Cited By ~ 2

Author(s):

Masahiro Nagaoka ◽

Toyonobu Maeda ◽

Masahiro Chatani ◽

Kazuaki Handa ◽

Tomoyuki Yamakawa ◽

...

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Bone Metabolism ◽

Mouse Models ◽

Bone Morphogenetic Protein 2 ◽

Bone Surface ◽

Bone Formation Rate ◽

Trabecular Thickness ◽

Tissue Volume ◽

Maqui Berry

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.

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Persistent Increase in Bone Turnover in Graves’ Patients with Subclinical Hyperthyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.11.6979 ◽

2000 ◽

Vol 85 (11) ◽

pp. 4157-4161 ◽

Cited By ~ 1

Author(s):

Yasuro Kumeda ◽

Masaaki Inaba ◽

Hideki Tahara ◽

Yasuko Kurioka ◽

Tetsuro Ishikawa ◽

...

Keyword(s):

Bone Turnover ◽

Bone Metabolism ◽

Antithyroid Drug ◽

Significant Negative Correlation ◽

Bone Alkaline Phosphatase ◽

Mineral Density ◽

Free T4 ◽

Bone Formation Markers ◽

Significant Attenuation ◽

Group B

Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mineral density. However, of patients with Graves’ disease (GD) maintained on antithyroid drug (ATD) treatment, some exhibit persistent suppression of TSH long after normalization of their serum free T3 (FT3) and free T4 (FT4) levels. The aim of this study was to examine whether bone metabolism is still enhanced in TSH-suppressed premenopausal GD patients with normal FT3 and FT4 levels after ATD therapy (n = 19) compared with that in TSH-normal premenopausal GD patients (n = 30), and to evaluate the relationship between serum TSH receptor antibody (TRAb), an indicator of disease activity of GD, and various biochemical markers of bone metabolism. No difference was found between the two groups in serum Ca, phosphorus, or intact PTH, or in urinary Ca excretion. Serum bone alkaline phosphatase (B-ALP), bone formation markers, and urinary excretions of pyridinoline (U-PYD) and deoxypyridinoline (U-DPD), which are bone resorption markers, were significantly higher in the TSH-suppression group than in the TSH-normal group (B-ALP, P < 0.05; U-PYD, P < 0.001; U-DPD, P < 0.001). For the group of all GD patients enrolled in this study, TSH, but neither FT3 nor FT4, exhibited a significant negative correlation with B-ALP (r = −0.300; P < 0.05), U-PYD (r= −0.389; P < 0.05), and U-DPD (r = −0.446; P < 0.05), whereas TRAb exhibited a highly positive and significant correlation with B-ALP (r = 0.566; P < 0.0001), U-PYD (r = 0.491; P < 0.001), and U-DPD (r = 0.549; P < 0.0001). Even in GD patients with normal TSH, serum TRAb was positively correlated with B-ALP (r = 0.638; P < 0.001), U-PYD (r = 0.638; P < 0.001), and U-DPD (r = 0.641; P < 0.001). In conclusion, it is important to achieve normal TSH levels during ATD therapy to normalize bone turnover. TRAb was not only a useful marker for GD activity, but was also a very sensitive marker for bone metabolism in GD patients during ATD treatment.

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Effects of resveratrol on bone metabolism and bone turnover related indexes in ovariectomized osteoporosis rats

Cellular and Molecular Biology ◽

10.14715/cmb/2020.66.5.17 ◽

2020 ◽

Vol 66 (5) ◽

pp. 92

Author(s):

Yujin Zhang ◽

Lin Deng ◽

Jiubo Fan ◽

Yazhi Zhang

Keyword(s):

Bone Turnover ◽

Bone Metabolism

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Urinary Osteocalcin as a Marker of Bone Metabolism

Clinical Chemistry ◽

10.1373/clinchem.2004.043901 ◽

2005 ◽

Vol 51 (3) ◽

pp. 618-628 ◽

Cited By ~ 54

Author(s):

Kaisa K Ivaska ◽

Sanna-Maria Käkönen ◽

Paul Gerdhem ◽

Karl J Obrant ◽

Kim Pettersson ◽

...

Keyword(s):

Bone Mass ◽

Bone Turnover ◽

Bone Metabolism ◽

Elderly Women ◽

Circadian Variation ◽

Serum Markers ◽

Seasonal Effects ◽

Molecular Forms ◽

Turnover Rates ◽

Turnover Markers

Abstract Background: Osteocalcin (OC) is produced by osteoblasts during bone formation, and circulating OC has been used in clinical investigations as a marker of bone metabolism. OC is excreted into urine by glomerular filtration and can be found in urine as midmolecule fragments. Methods: We developed and evaluated three immunoassays (U-MidOC, U-LongOC, and U-TotalOC) for the detection of various molecular forms of urine OC (U-OC). We evaluated the association of U-OC with other markers of bone turnover and with bone mass in 1044 elderly women and studied seasonal and circadian variation of U-OC. Results: U-OC correlated with other bone turnover markers [Spearman correlation (r), 0.30–0.57; P <0.0001], demonstrating the association between U-OC and skeletal metabolism. There was also a significant association between bone metabolism assessed by U-OC quartiles and bone mass assessed by total body bone mineral content (P <0.0001). The seasonal effects appeared to be rather small, but we observed a significant circadian rhythm similar to the one reported for serum OC with high values in the morning and low values in the afternoon. Conclusions: The three immunoassays had unique specificities toward different naturally occurring U-OC fragments. U-OC concentrations measured with any of these assays correlated with bone turnover rates assessed by conventional serum markers of bone metabolism. The measurement of OC in urine samples could be used as an index of bone turnover in monitoring bone metabolism.

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