Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

ABSTRACT Objective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass. Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment. Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab. Conclusion Bone loss was present in children with significant impairment of motor function, as well as decreased serum levels of bone resorption markers with new forms.

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Obesity and Bone Loss at Menopause: The Role of Sclerostin

Diagnostics ◽

10.3390/diagnostics11101914 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1914

Author(s):

Paolo Marzullo ◽

Chiara Mele ◽

Stefania Mai ◽

Antonio Nardone ◽

Massimo Scacchi ◽

...

Keyword(s):

Body Composition ◽

Lumbar Spine ◽

Femoral Neck ◽

Bone Turnover ◽

Postmenopausal Women ◽

Bone Health ◽

Bone Turnover Markers ◽

Turnover Markers ◽

Total Body

Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 ± 3.9 years; BMI, 46.0 ± 4.2 kg/m2) and 28 BMI-matched post-menopausal women (age, 55.5 ± 3.8 years; BMI, 46.1 ± 4.8 kg/m2) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p < 0.001), femoral neck (p < 0.0001), and total skeleton (p < 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p < 0.01), while menopausal status significantly predicted BMD at total hip (p < 0.01), femoral neck (p < 0.001) and total body (p < 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p < 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre- and postmenopausal women, its potential actions in obesity require further investigation.

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

10.21203/rs.3.rs-17423/v1 ◽

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.

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Determining the Required Vitamin D Level for Bone Health Based on Bone Turnover Markers

Korean Journal of Clinical Laboratory Science ◽

10.15324/kjcls.2017.49.4.337 ◽

2017 ◽

Vol 49 (4) ◽

pp. 337-344

Author(s):

Tuan Salwani Tuan Ismail ◽

Bayani Che Muda ◽

Roznie Aida Mohd Rosdi ◽

Azalina Zainuddin ◽

Salbiah Isa ◽

...

Keyword(s):

Vitamin D ◽

Bone Turnover ◽

Bone Health ◽

Bone Turnover Markers ◽

Turnover Markers

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

BMC Endocrine Disorders ◽

10.1186/s12902-020-00633-1 ◽

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.

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