scholarly journals Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study

2020 ◽  
Vol 183 (2) ◽  
pp. 181-189
Author(s):  
Rougin Khalil ◽  
Leen Antonio ◽  
Michaël R Laurent ◽  
Karel David ◽  
Na Ri Kim ◽  
...  
Keyword(s):  
Cohort Study ◽  
Calcium Phosphate ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Prospective Cohort ◽  
Phosphate Homeostasis ◽  
Adult Men ◽  
Early Effects

Objective Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design Prospective cohort study. Methods Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results Of 26 screened patients, 17 were included. The median age was 44 (range 20–75) years. The median time interval between baseline and first follow-up was 13 (6–27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4–12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01–0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7–35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

scholarly journals THU0402 SERUM MARKERS OF BONE RESORPTION, FORMATION, AND MINERALIZATION DURING 8 YEARS OF TNF-Α BLOCKING THERAPY IN PATIENTS WITH ANKYLOSING SPONDYLITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 438.1-439
Author(s):  
M. Siderius ◽  
A. Spoorenberg ◽  
S. Arends
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Mineralization ◽  
Serum Markers ◽  
Z Score ◽  
Tnf Α ◽  
Z Scores ◽  
Markers Of Bone Resorption

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by both excessive bone formation and bone loss. The bone turnover marker (BTM) bone-specific alkaline phosphatase (BALP) plays a central role in bone mineralization. Our previous study demonstrated that 3 years of TNF-α blocking therapy results in a significant increase in BALP.1However, longer follow-up is needed to investigate whether BALP stays elevated during TNF-α blocking therapy and also to explore the course of other BTM, osteocalcin (OC), procollagen type 1 N-terminal peptide (PINP) and serum type 1 collagen C-telopeptide (sCTX) in AS.Objectives:To evaluate serum markers of bone resorption, formation, and mineralization during 8 years of TNF-α blocking therapy in AS patients.Methods:Included were consecutive AS outpatients from the University Medical Center Groningen (UMCG) attending the Groningen-Leeuwarden Axial SpA (GLAS) cohort and who were treated with a maximum of 2 TNF-α blockers for at least 8 years. Patients were excluded when they used bisphosphonates at baseline or during follow-up. Data for a specific visit was coded as missing when patients either had experienced a fracture or received systemic corticosteroids within 1 year of that particular visit. Clinical and laboratory measurements were performed at baseline (before start of TNF-α blocking therapy), 3 and 6 months as well as 1, 2, 4, 6 and 8 years. Markers of bone formation OC, PINP and BALP, and marker of bone resorption sCTX were measured in serum. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. Serum levels of 25-hydroxyvitamin D (25(OH)D3) were assessed yearly. Generalized estimating equations were used to analyze BTM Z-scores over time within patients. Simple contrast was used to compare follow-up visits to baseline. P-values <0.05 were considered statistically significant.Results:In total, 37 AS patients were analyzed; 62% were male, 86% HLA-B27+, mean age was 38.6 ± 10.4 years, median symptom duration 14 years (IQR 10-25), median CRP 13 mg/L (IQR 6-25), and 30% had low vitamin 25(OH)D3 status (<50) at baseline. 35% of patients switched to a second TNF-α inhibitor during follow-up. ASDASCRPimproved significantly during treatment, from mean 3.8 ± 0.9 at baseline to 1.9 ± 0.9 after 8 years of follow-up (P<0.001). 25(OH)D3 levels were stable at group level, median 58 nmol/L (IQR 45-70) at baseline and 60 nmol/L (IQR 50-70) after 8 years. Bone regulation marker OC Z-score was found to be significantly increased only after 3 months of TNF-α blocking therapy compared to baseline. No significant changes during follow-up were found for collagen resorption marker sCTX Z-score. Collagen formation marker PINP Z-score was significantly increased after 3 and 6 months as well as 2 years of TNF-α blocking therapy. Bone mineralization marker BALP Z-score was significantly increased at all time points up to and including 2 years and returned to baseline levels during 4 to 8 years of TNF-α blocking therapy (Figure 1).Conclusion:In this subgroup of AS patients with established and active disease responding to TNF-α blocking therapy, we observed that the bone turnover balance favored bone formation during the first years of TNF-α blocking therapy, which corresponds to previously reported improvement in bone mineral density, especially at the lumbar spine.1New finding of our study is that after 8 years of treatment, markers of bone resorption, formation, and mineralization were all comparable to baseline values.References:[1]Arends et al. Arthritis Res Ther. 2012;14(2):R98Disclosure of Interests: :Mark Siderius: None declared, Anneke Spoorenberg: None declared, Suzanne Arends Grant/research support from: Grant/research support from Pfizer

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 POS1002 BASELINE CALPROTECTIN AND VISFATIN LEVELS PREDICT RADIOGRAPHIC SPINAL PROGRESSION AFTER 2 YEARS IN ANKYLOSING SPONDYLITIS PATIENTS ON TNF INHIBITOR THERAPY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 769.2-770
Author(s):  
J. Rademacher ◽  
M. Siderius ◽  
L. Gellert ◽  
F. Wink ◽  
M. Verba ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Bone Turnover ◽  
Radiographic Progression ◽  
Serum Levels ◽  
Tnf Inhibitor ◽  
Research Support

Background:Radiographic spinal progression determinates functional status and mobility in ankylosing spondylitis (AS)1.Objectives:To analyse whether biomarker of inflammation, bone turnover and adipokines at baseline or their change after 3 months or 2 years can predict spinal radiographic progression after 2 years in AS patients treated with TNF-α inhibitors (TNFi).Methods:Consecutive AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort2 starting TNFi between 2004 and 2012 were included. The following serum biomarkers were measured at baseline, 3 months and 2 years of follow-up with ELISA: - Markers of inflammation: calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) - Markers of bone turnover: bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide (sCTX), osteocalcin (OC), osteoprotegerin (OPG), procollagen typ I and II N-terminal propeptide (PINP; PIINP), sclerostin. - Adipokines: high molecular weight (HMW) adiponectin, leptin, visfatinTwo independent readers assessed spinal radiographs at baseline and 2 years of follow-up according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was defined as mSASSS change ≥2 units or the formation of ≥1 new syndesmophyte over 2 years. Logistic regression was performed to examine the association between biomarker values at baseline, their change after 3 months and 2 years and radiographic spinal progression. Multivariable models for each biomarker were adjusted for mSASSS or syndesmophytes at baseline, elevated CRP (≥5mg/l), smoking status, male gender, symptom duration, BMI, and baseline biomarker level (the latter only in models with biomarker change).Results:Of the 137 included AS patients, 72% were male, 79% HLAB27+; mean age at baseline was 42 years (SD 10.8), ASDAScrp 3.8 (0.8) and mSASSS 10.6 (16.1). After 2 years of follow-up, 33% showed mSASSS change ≥2 units and 24% had developed ≥1 new syndesmophyte. Serum levels of biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, whereas adipokine levels were not altered from baseline (Figure 1).Univariable logistic regression revealed a significant association of baseline visfatin (odds ratio OR [95% confidence interval] 1.106 [1.007-1.215]) and sclerostin serum levels (OR 1.006 [1.001-1.011]) with mSASSS progression after 2 years. Baseline sclerostin levels were also associated with syndesmophyte progression (OR 1.007 [1.001-1.013]). In multivariable logistic analysis, only baseline visfatin level remained significantly associated (OR 1.465 [1.137-1.889]) with mSASSS progression. Furthermore, baseline calprotectin showed a positive association with both, mSASSS (OR 1.195 [1.055-1.355]) and syndesmophyte progression (OR 1.107 [1.001-1.225]) when adjusting for known risk factors for radiographic progression.Univariable logistic regression showed that change of sclerostin after 3 months was associated with syndesmophytes progression (OR 1.007 [1.000-1.015), change of PINP level after 2 years was associated with mSASSS progression (OR 1.027 [1.003-1.052]) and change of visfatin after 2 years was associated with both measures of radiographic progression – mSASSS (OR 1.108 [1.004-1.224]) and syndesmophyte formation (OR 1.115; [1.002-1.24]). However, those associations were lost in multivariable analysis.Conclusion:Independent of known risk factors, baseline calprotectin and visfatin levels were associated with radiographic spinal progression after 2 years of TNFi. Although biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, these changes were not significantly related to radiographic spinal progression in our cohort of AS patients.References:[1]Poddubnyy et al 2018[2]Maas et al 2019Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:Judith Rademacher: None declared, Mark Siderius: None declared, Laura Gellert: None declared, Freke Wink Consultant of: AbbVie, Maryna Verba: None declared, Fiona Maas: None declared, Lorraine M Tietz: None declared, Denis Poddubnyy: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Novartis, Suzanne Arends Grant/research support from: Pfizer.

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