scholarly journals Assessment of Bone Turnover Biomarkers in Lead-Battery Workers with Long-Term Exposure to Lead

Author(s):  
Kalahasthi Ravibabu ◽  
Tapu Barman ◽  
Bhavani Shankara Bagepally

Background: The major portion of lead in the body resides in skeletal system. The bone turnover affects the release of lead into the circulation from bones. The bone turnover biomarkers (BTM) in lead-battery workers with long-term exposure to lead have not been explored yet. Objective: To evaluate the BTM (formation and resorption) in lead-battery workers with long-term exposure to lead in lead-battery manufacturing plant. Methods: 176 male lead-exposed workers and 80 matched comparison group were studied. All participants were examined for blood lead levels (BLLs), bone formation biomarkers—serum osteocalcin (OC), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP)—and bone resorption biomarkers—serum pyridinoline (PYD), deoxypyridinoline (DPYD), tartarate-resistant acid phosphatase-5b (TRACP-5b), and urinary hydroxyproline (UHYP). Results: We found a significantly higher bone formation biomarkers such as BALP (p=0.007) and bone resorption biomarkers, eg, PYD (p=0.048), TRCAP-5b (p=0.001), and UHYP (p=0.001) in lead-exposed workers. A significant (p=0.041) negative correlation (ρ -0.128) was noted between BLLs and OC. A significant positive correlation was noted between BLLs and TRACP-5b (ρ 0.176, p=0.005) and UHYP (ρ 0.258, p=0.004). Serum OC (p=0.040) and UHYP (p=0.015) levels changed significantly with BLL level. Bone resorption biomarkers levels—PYD, TRACP-5b, and BALP—were higher among those with higher BLLs levels. The duration of exposure was significantly associated with BALP (p=0.037), DPYD (p=0.016), TRACP5b (p=0.001), and UHYP (p=0.002) levels. Conclusion: Long-term lead exposure affects the bone turnover.

Author(s):  
A. V. Sukhova ◽  
E. N. Kryuchkova

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.


2018 ◽  
Vol 4 (1) ◽  
pp. 132-137 ◽  
Author(s):  
Naoki Kondo ◽  
Noriaki Yamamoto ◽  
Kei Watanabe ◽  
Naoto Endo

There is minimal information on bone Histomorphometric characteristics in ankylosing spondylitis. We here report a case of a 36-year-old Japanese male that suffered from lumbago and could not gaze in the forward direction. Ultimately, a diagnosis of ankylosing spondylitis was made, and vertebroplasty was performed to correct the third lumbar spine. Histomorphometry of the iliac bone showed reduced bone volume parameters (bone volume, and trabecular thickness and width) than reference values. In addition, bone formation parameters (osteoid thickness and osteoblast surface per bone surface) and bone resorption parameters (eroded surface per bone surface and osteoclast number per bone surface) were also lower than reference values, indicating low bone turnover. By contrast, there was not a clear trend in bone resorption markers: bone- pecific alkaline phosphatase (17 U/l) was normal, TRACP-5b (136 mU/dl) was slightly lower, urinary N-terminal telopeptide (45.3 nmol BCE/mmol Cr) was normal, and deoxypyridinoline (9.1 nM/mM Cre) was higher than reference values. However, there was deficiency in 25-hydroxy vitamin D (25-OH-D; 14.4 ng/ml). This case highlights the rare possibility of performing bone histomorphometry, and indicates that a low bone volume and low bone turnover (in both bone formation and resorption) are characteristics of ankylosing spondylitis, although bone formation markers (bone-specific alkaline phosphatase) and bone mineral density are within the normal range. The possibility of a serum 25-OH-D deficient status in ankylosing spondylitis should be further considered.


Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  

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.


1996 ◽  
Vol 6 (S1) ◽  
pp. 250-250
Author(s):  
HW Woitge ◽  
M Müller ◽  
P Bärtsch ◽  
B Friedmann ◽  
MJ Seibel ◽  
...  

1982 ◽  
Vol 63 (2) ◽  
pp. 153-160 ◽  
Author(s):  
J. Reeve ◽  
J. R. Green ◽  
R. Hesp ◽  
Patricia Hulme

1. Calcium balances and formation rates of new bone measured with an improved tracer technique using 85Sr have been determined simultaneously in 21 patients with idiopathic osteoporosis and vertebral crush fractures. 2. A weak positive association was found between calcium balance and the kinetically measured calcium accretion rate, which is the sum of the true rate of bone formation and various long-term exchange processes. 3. The more negative balances were associated with significantly greater early loss of tracer taken up into bone by ‘accretion’, so that long-term (> 200 day) uptake was reduced. 4. This indicates that patients actively losing bone mineral have lower true rates of bone formation and higher rates of long-term exchange than their fellow patients who are more nearly in calcium equilibrium. 5. No statistically significant association was found between measured rates of bone resorption and calcium balance.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 71-71
Author(s):  
Joseph Roberts ◽  
Moriah Bellissimo ◽  
Kaitlin Taibl ◽  
Karan Uppal ◽  
Dean Jones ◽  
...  

Abstract Objectives Optimal bone health is maintained through a remodeling cycle consisting of resorption followed by formation. Procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptides of type I collagen (CTX) are biomarkers of bone metabolism that capture changes in bone formation and bone resorption, respectively. This study aimed to identify unique metabolic pathways related to bone turnover markers (BTMs) in healthy young adults. Methods This cross-sectional study included 34 healthy, young adults (19 females, average age 27.8 years). Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Fasting plasma was analyzed using dual column liquid chromatography and ultra-high-resolution mass spectrometry for metabolomics. Serum levels of P1NP and CTX were measured with ELISA. Linear regression and pathway enrichment analyses were used to identify metabolic pathways related to the BTMs. Results All participants had a normal whole-body BMD T-score. Metabolites significantly associated with P1NP (at P &lt; 0.05) were significantly enriched in pathways linked to the TCA cycle, pyruvate metabolism, and metabolism of B-vitamins important for energy production (e.g., niacin, thiamin). Other nutrition-related metabolic pathways associated with P1NP were amino acid (proline, arginine, glutamate) and vitamin C metabolism, which are important for collagen formation. Metabolites were associated with CTX levels (at P &lt; 0.05), which were enriched within lipid and fatty acid beta-oxidation metabolic pathways, as well as fat soluble micronutrients pathways including, vitamin D metabolism, vitamin E metabolism, and bile acid biosynthesis. Conclusions High-resolution metabolomics identified several distinct plasma metabolic pathways, including energy-yielding metabolic pathways and pathways related to fatty acid, amino acid, and micronutrient metabolism that were associated with markers of bone formation and bone resorption. Characterizing these metabolism-related pathways associated with BTMs in healthy adults is an important step towards understanding the metabolic perturbations that lead to low bone mass in older and clinical populations. Funding Sources National Institutes of Health and Emory University.


1977 ◽  
Vol 232 (6) ◽  
pp. E535
Author(s):  
B Haldimann ◽  
J P Bonjour ◽  
H Fleisch

The effect of calcium deprivation on the various calcium fluxes was studied in growing rats either sham-operated (SHAM), thyroparathyroidectomized (TPTX), or thyroparathyroidectomized and supplemented with parathyroid hormone (PTH) (TPTX + PTH). In SHAM rats a decrease in the net absorption of calcium (Vna) has no influence on calcemia or on bone formation (Vo+), but leads to an increase in bone resorption (Vo-). In TPTX rats a decrease in Vna induces a decrease in calcemia and in Vo+ but still causes an increase in Vo-. The same is true in TPTX + PTH rats although all the variables measured are increased. In TPTX rats, both without and with PTH, a linear correlation exists between calcemia and Vo+ suggesting that calcemia influences bone formation. Furthermore, it appears that PTH is important in regulating bone turnover, but that the adaptation of Vo- to a change in Vna can occur in the absence or in the presence of a constant amount of this hormone. The mechanism of regulating this adaptation of bone resorption is still unknown.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 506-506
Author(s):  
Evangelos Terpos ◽  
Deborah Heath ◽  
Amin Rahemtulla ◽  
Kostas Zervas ◽  
Andrew Chantry ◽  
...  

Abstract Bortezomib is a proteasome inhibitor, which is currently indicated for the treatment of relapsed/refractory myeloma (MM). Although the anti-myeloma effect of bortezomib has been clearly demonstrated, its effect on bone metabolism is still unclear. There are recent reports that bortezomib increases serum alkaline phosphatase (ALP) activity, which is consistent with enhanced osteoblast function. The aim of this study was to evaluate the effect of bortezomib on bone turnover in 34 patients with relapsed MM. Bortezomib was given alone at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of a 3-week cycle for 4 cycles. Responders could continue for 4 more cycles, while non-responders could continue therapy with the addition of dexamethasone. The following serum indices were measured on day 1 of cycle 1, and then on day 21 of cycles 4 and 8: osteoblast inhibitor dickkopf-1 (DKK-1); osteoclast regulators: soluble RANKL (sRANKL) and osteoprotegerin (OPG); bone resorption markers: C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase type-5b (TRACP-5b); and bone formation markers: bone-specific ALP (bALP) and osteocalcin (OC). We also studied 33 healthy controls of similar gender and age. The objective response rate after 4 cycles of therapy was 66%: CR 8% and PR 58%. Sixteen responders and 3 non-responders continued on therapy for 4 more cycles. Myeloma patients at baseline had increased values of DKK-1 (p=0.007), sRANKL, sRANKL/OPG ratio, and both markers of bone resorption (p&lt;0.0001) when compared to controls. In contrast, bone formation as assessed by serum bALP and OC was significantly reduced (p&lt;0.001). There was a strong correlation between bone lytic disease and serum CTX (r=0.59, p&lt;0.01), and sRANKL (r=0.4, p=0.03). Patients with severe bone disease (&gt;9 lytic lesions, n=7) had elevated values of DKK-1 compared with all others (mean±SD: 223.4±264.4 ng/mL vs. 84±62.4 ng/mL; p=0.01). Moreover, serum levels of DKK-1 correlated with CTX levels (r=0.39, p=0.04), and weakly with bALP concentrations (r=−0.32, p=0.09). The administration of bortezomib produced a significant reduction of DKK-1 (p=0.035), sRANKL (p=0.01), CTX and TRACP-5b (p&lt;0.001) after 4 cycles, which was still seen after 8 cycles of treatment (p&lt;0.01). Bortezomib also produced a dramatic increase in both markers of bone formation, bALP and OC, after 4 and 8 cycles of therapy (p&lt;0.01). Responders tended to have lower initial levels of DKK-1 compared with non-responders. Patients who achieved a CR or vgPR after 4 cycles of bortezomib had greater elevation of bALP than all others: mean±SD of increase: 306.3%±556.9% vs. 45.8%±56.5%; p=0.02. It is of interest that 3/4 non responders also had an increase in bALP (mean: 39.6%) after 4 cycles of bortezomib. There was no other correlation between response to therapy and alteration of bone markers. No healing of the lytic lesions was observed even in CR patients. This study suggests that bortezomib reduces serum levels of DKK-1 and RANKL, irrespective of response to therapy, in patients with relapsed myeloma and thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 493-493 ◽  
Author(s):  
O. Katsarou ◽  
Evangelos Terpos ◽  
P. Hatzismalis ◽  
S. Provelengios ◽  
T. Adraktas ◽  
...  

Abstract Osteoporosis has been recently recognized as a comorbidity factor, which affects significantly the quality of life in hemophilia patients. Prolonged immobilization and severity of arthropaphy have been considered as the major factors contributing to the pathogenesis of osteoporosis in hemophilia. However, the exact mechanisms of bone loss have not been fully clarified in this disorder. The aim of this study was to evaluate the incidence of osteoporosis in hemophilia patients, and investigate the possible correlations with clinical and laboratory data in an attempt to better understand the pathogenetic mechanisms that are involved in its development. Ninety-three hemophilia patients were evaluated. Their median age was 36 years (range: 24–46 years). Eighty patients (86%) had severe and 13 patients (13%) moderate haemophilia. Fifty-seven patients (61%) were HIV negative and 36 (38%) HIV positive. The severity of hemophilic arthropahty was assessed using WFH clinical score and Petterson radiological score in all patients. Bone mineral density of the lumbar spine(LS) and the femoral neck(FN) was measured using DEXA technique in 78 out of 93 patients. Bone turnover was studied by the measurement of a series of serum indices: bone resorption markers [N- and C-telopeptide of type-I collagen (NTX and CTX, respectively), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], bone formation markers [bone-alkaline phosphatase (bALP), and osteocalcin], and osteoclast stimulating factors [receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor-alpha]. Osteopenia(−2,5<T-score<−1.5) or osteoporosis (T-score<−2,5) was found in 83.9% and 60% of the patients in the FN and LS respectively. Osteoporosis was more common among HIV positive patients in both FN (65.3%vs.41.6%; p=0.007) and LS (17.86%vs.5.41%, p=0.004).The severity of osteoporosis in the FN correlated with patients’ total clinical and radiological score (p=0.001). Hemophilia patients showed increased serum levels of all markers of bone resorption and bALP compared with 15 controls of similar gender and age (median NTX: 19.4 vs. 17.4 nM BCE, p=0.018; CTX: 0.61 vs. 0.47 ng/mL, p=0.028; TRACP-5b: 2.7 vs. 1.3 U/L, p<0.01; and bALP: 20.0 vs. 16.9 U/L, p=0.048; for patients and controls, respectively). This increased osteoclastic activity was not found to be mediated by RANKL/RANK/OPG system as we observed no difference in terms of sRANKL/OPG ratio between patients and controls. Therefore it seems that other factors are involved in the increased bone resorption observed in hemophiliacs. In multivariate analysis, HIV infection (p=0.05) and total clinical score (p=0.001), were found to be independent prognostic factors for developing osteoporosis. Our study has shown that the incidence of osteoporosis is high among hemophilia patients and is related to the severity of hemophilic arthropathy. We report for the first time that hemophilia patients have high bone turnover, which seems not to be due to an imbalance of the RANKL/OPG system. HIV infection increases the negative effects of hemophilia on bone metabolism and may contribute to the pathogenetic mechanisms involved in osteoporosis development.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 638-638 ◽  
Author(s):  
Raffaele Ratta ◽  
Elena Verzoni ◽  
Francesco Pantano ◽  
Paolo Grassi ◽  
Antonia Martinetti ◽  
...  

638 Background: In-vitro studies have shown that cabozantinib has a strong inhibitory action on osteoclast differentiation and bone-resorption activity. The aim of this analysis was to investigate the effects of cabozantinib on bone turnover markers in patients (pts) with metastatic renal cell carcinoma (mRCC). Methods: We included mRCC pts treated with cabozantinib within the Italian Managed Access Program (MAP) at the Istituto Nazionale Tumori of Milan (Italy). Plasma samples from every patient were collected at baseline and after 3 and 6 months of treatment. The bone resorption markers C-terminal telopeptide of type I collagen (CTx) and tartrate-resistant acid phosphatase isoenzyme 5b (TRACP 5b), the osteoclastogenesis markers osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), vitamin D and parathormone (PTH) were measured by immunometric assay techniques. Data were analyzed using the RM One-Way ANOVA test with Greenhouse-Geisser correction followed by uncorrected Fisher’s LSD multiple comparison tests with individual variances computed for each comparison. Statistical tests were performed using the program GraphPad Prism (San Diego, CA). Results: Twenty-two pts have been treated with cabozantinib. Mature data were available for 11 pts. Analysis of TRACP 5b, OPG, RANKL and vitamin D did not show any significant variations during treatment with cabozantinib. CTx showed a significant reduction after 6 months of treatment (MV 171.5 pg/mL, STD 208.4) from baseline (mean value [MV] 352.2 pg/mL, standard deviation [STD] 210.1) (p = 0.0439) in the whole study population. PTH levels significantly increased after 3 months of treatment (MV 86.79 pg/mL, STD 34.99) from baseline (MV 30.77 pg/mL, STD 12.64) (p = 0.0003), while significantly decreased after 6 months (MV 75.01 pg/mL, STD 53.1) (p = 0.0174). Conclusions: Our data suggested that cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx; it was also associated with an asymptomatic transient secondary increase of parathormone. This is the first clinical evidence on effects of cabozantinib on bone metabolism in a small population of mRCC pts.


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