scholarly journals The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rosemary Dineen ◽  
Lucy-Ann Behan ◽  
Grainne Kelleher ◽  
Mark J. Hannon ◽  
Jennifer J. Brady ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bone Formation ◽  
Bone Turnover ◽  
Negative Correlation ◽  
Bone Health ◽  
Bone Turnover Markers ◽  
Serum Cortisol ◽  
Chromatography Mass Spectrometry ◽  
Bone Formation Markers ◽  
Turnover Markers

Abstract Background Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Conclusion Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Trial registration Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37. Registration date: 07-09-2007.

scholarly journals The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy

2020 ◽  
Author(s):  
Rosemary Dineen ◽  
Lucy-Ann Behan ◽  
Grainne Kelleher ◽  
Mark J Hannon ◽  
Jennifer J Brady ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bone Formation ◽  
Bone Turnover ◽  
Replacement Therapy ◽  
Negative Correlation ◽  
Bone Health ◽  
Bone Turnover Markers ◽  
Serum Cortisol ◽  
Bone Formation Markers ◽  
Turnover Markers

Abstract Background: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group.Methods: Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-hour serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-hour urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS).Results: Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20mg/10mg) [670.5 (IQR 621-809.2)] compared to those on dose C (10mg/5mg) [562.8 (IQR 520.1-619.6), p=0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC[1-49] (r=-0.42, p=0.03), and PINP (r=-0.49, p=0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC[1-49] (r=-0.41, p=0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r=-0.39, p=0.04), and OC[1-49] (r=-0.35, p=0.06).Conclusion: Serum cortisol and cortisone and total urinary corticosteroid metabolites are associated with alterations in bone turnover markers even at replacement doses of hydrocortisone suggesting a potentially negative role of tissue-specific metabolism of glucocorticoids on bone metabolism in patients receiving hydrocortisone replacement therapy.

scholarly journals Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Pawel Szulc
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Fragility Fractures ◽  
Older Men ◽  
Testosterone Replacement Therapy ◽  
Mineral Density ◽  
Bone Formation Markers ◽  
Turnover Markers

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men.

The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid

Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Metabolism ◽  
Bone Turnover Markers ◽  
Control Group ◽  
Bone Resorption Marker ◽  
Amino Terminal ◽  
Normal People ◽  
Turnover Markers

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.

scholarly journals Serum levels of bone formation and resorption markers in relation to vitamin D status in professional gymnastics and physically active men during upper and lower body high-intensity exercise

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Mieszkowski ◽  
Andrzej Kochanowicz ◽  
Elżbieta Piskorska ◽  
Bartłomiej Niespodziński ◽  
Joanna Siódmiak ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Serum Levels ◽  
Type I ◽  
Vitamin D Metabolites ◽  
Physically Active ◽  
Turnover Markers

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis

2011 ◽  
Vol 71 (1) ◽  
pp. 71-74 ◽  
Author(s):  
L Senolt ◽  
H Hulejova ◽  
O Krystufkova ◽  
S Forejtova ◽  
L Andres Cerezo ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Serum Levels ◽  
Total Serum ◽  
Mineral Density ◽  
Spinal Involvement ◽  
Turnover Markers ◽  
Dickkopf 1

ObjectiveDickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH).MethodsSerum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH.ResultsThe levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1.ConclusionThese observations indicate that DKK-1 may play a significant role in bone formation during DISH.

scholarly journals Specific Effects of Anorexia Nervosa and Obesity on Bone Mineral Density and Bone Turnover in Young Women

2019 ◽  
Vol 105 (4) ◽  
pp. e1536-e1548 ◽  
Author(s):  
Laurent Maïmoun ◽  
Patrick Garnero ◽  
Thibault Mura ◽  
David Nocca ◽  
Patrick Lefebvre ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Anorexia Nervosa ◽  
Bone Formation ◽  
Bone Turnover ◽  
Young Women ◽  
Bone Turnover Markers ◽  
The Other ◽  
Mineral Density ◽  
Turnover Markers ◽  
Markers Of Bone Formation

Abstract Objective The threefold aim was to (1) compare areal bone mineral density (aBMD), bone turnover markers, and periostin levels in young women with either anorexia nervosa (AN) or obesity (OB) and controls (CON); (2) model the profiles according to age; and (3) determine the parameters associated with aBMD. Subjects and Methods One hundred and fifty-two young women with ages ranging from 16.0 to 27.0 years were subdivided into 3 groups (AN, OB, CON). The CON group was age-matched by ±6 months. aBMD, bone turnover markers, and periostin levels were evaluated. Results aBMD modeling showed that hip aBMD was higher in OB than in the other 2 groups from 19 years, and AN presented lower values than CON from 21 years. aBMD at the lumbar spine was higher in older OB and CON women, starting from 20 to 22 years, but in AN the difference with the other 2 groups increased with age. Periostin levels were lower in OB than in AN or CON, but no variation with age was observed. Compared with controls, OB and AN presented similarly lower markers of bone formation, although markers of bone resorption were lower in OB and higher in AN. A modeling approach showed that markers of bone formation and resorption were lower in older than in younger CON, whereas the values of these bone markers remained relatively constant in AN and OB. In all groups, lean body mass (LBM) was the parameter most positively correlated with aBMD. Conclusion This study demonstrated that weight extremes (AN or OB) influence aBMD, bone remodeling and periostin profiles. Moreover, factors related to aBMD were specific to each condition, but LBM was the parameter most consistently associated with aBMD.

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