Prospective Evaluation of the Bone Anabolic Effect of Bortezomib in Relapsed Multiple Myeloma (MM) Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2719-2719 ◽  
Author(s):  
Maurizio Zangari ◽  
Federica Cavallo ◽  
Larry Suva ◽  
Joshua Dilley ◽  
Guido Trico ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Biopsy ◽  
Single Agent ◽  
Bone Architecture ◽  
Entire Study ◽  
Osteoblast Activity ◽  
Bone Biopsies ◽  
Tetracycline Labeling

Abstract Bortezomib (B) has been shown to increase osteoblast activity and inhibit osteoclast formation, thus promoting bone formation. We have previously reported a correlation between increased alkaline phosphatase (ALP) and the response to B in patients with MM. We now report results of a detailed prospective study examining the skeletal effects of B treatment in MM patients using histomorphometry, micro computed tomography (microCT) and markers of bone metabolism. Methods: Single agent B (1.3 mg/m2 patients 1–10; 1mg/m2 patient 11–20), was administered on days 1, 4, 8 and 11 on a 21 day intervals for a total of 3 cycles; no patients were receiving concurrent bisphosphonates or steroids during the entire study period. The dynamic indices of bone turnover were prospectively evaluated via tetracycline labeling prior to transiliac bone biopsies obtained at baseline and after 3 cycles of treatment. Biopsy specimens were examined by high-resolution microCT prior to histomorphometric analyses. Architectural parameters such as bone volume/total volume (BVTV), trabecular number (TbN), and thickness (Tb.Th) were recorded. Osteocalcin, and alkaline phosphatase on days 1,4,8,11 were measured before and after each B dose and every 4 hours thereafter, daily for the other days of the treatment cycle. Results: Histomorphometric analyses were compared in 7 of the 11 patients who completed the trial. All 11 patients underwent bone biopsy at baseline nine of those 11 at the end of the study (2 samples were not adequate). Baseline BV/TV values ranged from 13% to 80%. After 3 cycles of B treatment % increase (mean 37%) in BV/TV was shown in 6 of 7 patients (P<0.034). Tb.Th was also increased from baseline (range 20%–456%) in 5 of 7 patients (71%) who responded to B. Histological bone histomorphometry demonstrated a lack of osteoid formation and osteoblast activity at baseline and a marked increased in osteoid and osteoblast numbers on trabecular and cortical bone surface following B treatment. Tetracycline incorporation into bone was observed in only 2 of 11 of patients (18%) at baseline, reflecting the extremely low levels of bone turnover in MM patients prior to treatment. However, post-B tetracycline labeling was observed in 7 of 11 (63%) samples (p<0.03; baseline vs post treatment score changes), reflecting the dramatic increases in bone turnover elicited by B treatment. Interestingly, after B treatment, the rate of bone formation was accelerated in the 2 patients with measurable baseline tetracycline labeling. Baseline osteocalcin values were below the reference intervals (11–50 ng/ml) in 10 of 11 patients but increased in 9 of 11 patients at the end of the third B cycle. Overall osteocalcin changes increased from baseline by 403% (p<0.037). BALP ranged from 4.5 to 48.4 ug/l at baseline and increased in 6 of 10 patients following B treatment. Conclusion: In this first prospective single agent B study we demonstrate that even a short course (3 cycles or 12 doses) of B treatment has a significant and potent anabolic bone effect in MM patients, demonstrated by serum turnover markers, micro-CT measures of bone architecture and by static and dynamic histomorphometry.

MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Bone Turnover ◽  
Diagnostic Accuracy ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
Bone Formation Rate ◽  
Suitable Alternative ◽  
Predictive Values ◽  
Bone Biopsies ◽  
Low Bone Turnover ◽  
Tetracycline Labeling

Abstract Background and Aims A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover. Method Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100). Results All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p &lt; 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1. Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm&gt;5.4%, OcPm&gt;1.5%, and OAr&gt;2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%. Conclusion Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.

HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 3024-3030 ◽  
Author(s):  
Therese Standal ◽  
Niels Abildgaard ◽  
Unn-Merete Fagerli ◽  
Berit Stordal ◽  
Øyvind Hjertner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Disease ◽  
Nuclear Translocation ◽  
Osteolytic Lesion ◽  
Bmp Signaling ◽  
Myoid Cell ◽  
Osteoblast Activity

AbstractThe bone disease in multiple myeloma is caused by an uncoupling of bone formation from bone resorption. A key difference between patients with and patients without osteolytic lesion is that the latter have fewer and less active osteoblasts. Hepatocyte growth factor (HGF) is often produced by myeloma cells and is found at high concentrations in the bone marrow of patients with multiple myeloma. Here we show that HGF inhibited bone morphogenetic protein (BMP)–induced in vitro osteoblastogenesis. Thus, HGF inhibited BMP-induced expression of alkaline phosphatase in human mesenchymal stem cells (hMSCs) and the murine myoid cell line C2C12, as well as mineralization by hMSCs. Furthermore, the expression of the osteoblast-specific transcription factors Runx2 and Osterix was reduced by HGF treatment. HGF promoted proliferation of hMSCs, and the BMP-induced halt in proliferation was overridden by HGF, keeping the cells in a proliferative, undifferentiating state. BMP-induced nuclear translocation of receptor-activated Smads was inhibited by HGF, providing a possible explanation of how HGF inhibits BMP signaling. The in vitro data were supported by the observation of a negative correlation between HGF and a marker of osteoblast activity, bone-specific alkaline phosphatase (rho = −0.45, P = .008), in sera from 34 patients with myeloma. These observations suggest that HGF inhibits bone formation in multiple myeloma.

Spectrum of bone pathologies in chronic kidney disease

2015 ◽  
Author(s):  
Stuart M. Sprague ◽  
James M. Pullman
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Formation ◽  
Bone Disease ◽  
Bone Biopsy ◽  
Fibroblast Growth Factor 23 ◽  
Osteitis Fibrosa ◽  
Adynamic Bone Disease ◽  
Osteoblast Activity ◽  
Adynamic Bone

Histologic bone abnormalities begin very early in the course of chronic kidney disease. The KDIGO guidelines recommend that bone disease in patients with chronic kidney disease should be diagnosed on the basis of bone biopsy examination, with bone histomorphometry. They have also proposed a new classification system (TMV), using three key features of bone histology—turnover, mineralization, and volume—to describe bone disease in these patients. However, bone biopsy is still rarely performed today, as it involves an invasive procedure and highly specialized laboratory techniques. High-turnover bone disease (osteitis fibrosa cystica) is mainly related to secondary hyperparathyroidism and is characterized by increased rates of both bone formation and resorption, with extensive osteoclast and osteoblast activity, and a progressive increase in peritrabecular marrow space fibrosis. On the other hand, low-turnover (adynamic) bone disease involves a decline in osteoblast and osteoclast activities, reduced new bone formation and mineralization, and endosteal fibrosis. The pathophysiological mechanisms of adynamic bone include vitamin D deficiency, hyperphosphataemia, metabolic acidosis, inflammation, low oestrogen and testosterone levels, bone resistance to parathyroid hormone, and high serum fibroblast growth factor 23. Mixed uraemic osteodystrophy describes a combination of osteitis fibrosa and mineralization defect. In the past few decades, an increase in the prevalence of mixed uraemic osteodystrophy and adynamic bone disease has been observed.

Bone Turnover In Multiple Myeloma: Impact Of Bortezomib-Based Induction Therapy, High-Dose Melphalan, and Lenalidomide Consolidation On Osteoblast and Osteoclast Function Within The GMMG-MM5 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1863-1863 ◽  
Author(s):  
Anja Seckinger ◽  
Tobias Meißner ◽  
Uta Bertsch ◽  
Hans Salwender ◽  
Jan Dürig ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Turnover ◽  
Induction Therapy ◽  
Research Funding ◽  
Induction Treatment ◽  
High Dose ◽  
Myeloma Cells ◽  
Osteoblast Activity ◽  
Osteoclast Function ◽  
High Dose Melphalan

Abstract Introduction In multiple myeloma, initially, there are increased numbers of osteoclasts showing increased activity, but bone formation by osteoblasts is keeping step. In later stages, parts of the bone remodeling compartments are disrupted by the interaction with myeloma cells leading to increased bone resorption which can no longer be compensated (myeloma bone disease, uncoupling of bone formation and bone resorption). Lenalidomide and bortezomib have been shown to target both, myeloma cells and the microenvironment: lenalidomide inhibits osteoclastogenesis, bortezomib is also able to stimulate osteoblast differentiation leading to increased bone formation. Aim of this study is to evaluate the impact of bortezomib-based induction treatment, high-dose therapy, and lenalidomide consolidation on alterations of bone turnover, i.e. surrogates of osteoblast- (osteocalcin, OC) and osteoclast- (collagen type I fragments, CTX-I) function, and their induction by myeloma cells (DKK1-level). Methods Serum was collected during routine sampling within the GMMG-MM5 trial (EudraCT 2010-019173-16), and levels of CTX-I, OC, and DKK1 were assessed by ELISA in triplicates using commercially available assays according to the manufacturer’s instructions (RnD Systems and Immunodiagnostic Systems). The following time points were assessed: at inclusion (n=365), after induction therapy with either PAd (n=88) or VCD (n=84), stem cell mobilization using CAD (n=69), high-dose melphalan (n=92), and 2 months lenalidomide consolidation (n=92). Up to now, serum samples of 69 patients were measured sequentially at five time points in line with the GMMG-MM5 trial. DKK1 levels were correlated with the expression in CD138-purified myeloma cells (Affymetrix microarrays, n=365). Results Prior to treatment, CTX-I levels are increased, those of OC decreased compared to healthy donors (uncoupled bone turnover). DKK1 protein levels are increased and correlate with DKK1-expression in myeloma cells. After induction therapy, osteoclast activity (CTX-I) is decreased below normal values. PAd unlike VCD further decreases osteoblast activity (OC-levels); DKK1-levels are normalized. Subsequent treatment further decreases DKK1-levels below normal values and blocks osteoclast function. After 2 months lenalidomide consolidation, no normalization of osteoblast activity is found. Conclusion The main impact on bone turnover by bortezomib-based induction treatment is a reduction of osteoclast activity alongside a decrease in DKK1-levels. During the reported period, no normalization of decreased osteoblast function was observed. Disclosures: Seckinger: Novartis Pharma: Research Funding. Goldschmidt:Novartis Pharma: Research Funding. Hose:Novartis Pharma: Research Funding.

scholarly journals The Effect of Bed Rest on Bone Turnover in Young Women Hospitalized for Anorexia Nervosa: A Pilot Study

2009 ◽  
Vol 94 (5) ◽  
pp. 1650-1655 ◽  
Author(s):  
Amy D. DiVasta ◽  
Henry A. Feldman ◽  
Ashley E. Quach ◽  
Maria Balestrino ◽  
Catherine M. Gordon
Keyword(s):  
Alkaline Phosphatase ◽  
Anorexia Nervosa ◽  
Bone Formation ◽  
Bone Turnover ◽  
Weight Bearing ◽  
Tertiary Care ◽  
Bed Rest ◽  
Short Term ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase

Abstract Context: Malnourished adolescents with anorexia nervosa (AN) requiring medical hospitalization are at high risk for skeletal insults. Even short-term bed rest may further disrupt normal patterns of bone turnover. Objective: The objective of the study was to determine the effect of relative immobilization on bone turnover in adolescents hospitalized for AN. Design: This was a short-term observational study. Setting: The study was conducted at a tertiary care pediatric hospital. Study Participants: Twenty-eight adolescents with AN, aged 13–21 yr with a mean body mass index of 15.9 ± 1.8 kg/m2, were enrolled prospectively on admission. Intervention: As per standard care, all subjects were placed on bed rest and graded nutritional therapy. Main Outcome Measure: Markers of bone formation (bone specific alkaline phosphatase), turnover (osteocalcin), and bone resorption (urinary N-telopeptides NTx) were measured. Results: During the 5 d of hospitalization, serum osteocalcin increased by 0.24 ± 0.1 ng/ml · d (P = 0.02). Urine N-telopeptides reached a nadir on d 3, declining −6.9 ± 2.8 nm bone collagen equivalent per millimole creatinine (P = 0.01) but returned to baseline by d 5 (P &gt; 0.05). Bone-specific alkaline phosphatase exhibited a decline that was strongly age dependent, being highly significant for younger subjects only [age 14 yr: −0.42 ± 0.11 (P = 0.0002); age 18 yr: −0.03 ± 0.08 (P = 0.68)]. Age had no effect on other outcome measures. Conclusion: Limitation of physical activity during hospitalization for patients with AN is associated with suppressed bone formation and resorption and an imbalance of bone turnover. Future interventional studies involving mechanical stimulation and/or weight-bearing activity are needed to determine whether medical protocols prescribing strict bed rest are appropriate.

scholarly journals P0885THE RELATIONSHIP BETWEEN BONE REGULATORY MARKERS AND BONE TURNOVER IN RENAL OSTEODYSTROPHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Syazrah Salam ◽  
Orla Gallagher ◽  
Fatma Gossiel ◽  
Arif Khwaja ◽  
Richard Eastell
Keyword(s):  
Bone Formation ◽  
Bone Turnover ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
Formation Rate ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Bone Formation Rate ◽  
Bone Formation Markers ◽  
The Relationship

Abstract Background and Aims Renal osteodystrophy is common in advanced chronic kidney disease (CKD) patients and is characterized by abnormal bone turnover and mineralization. Parathyroid hormone (PTH) increases bone turnover through osteoblast and osteoclast activation. Osteoprotegerin (OPG) is a decoy receptor of receptor activator of nuclear factor kappa-β ligand and thus, inhibits osteoclast maturation. Meanwhile, sclerostin is an inhibitor of the Wnt signalling pathway and thus, inhibits osteoblast maturation. We aimed to assess the relationship between these bone regulatory markers and bone turnover as assessed by bone histomorphometry and bone turnover markers (BTMs). Method We recruited 43 CKD patients with eGFR&lt;30ml/min/1.73m2 or on dialysis. Fasting serum samples were analysed using Immunodiagnostic Systems automated assays (Boldon, UK) for intact PTH (iPTH) and BTMs such as bone alkaline phosphatase (bALP) and intact procollagen type 1 N-terminal propeptide (intact PINP) which are bone formation markers, and tartrate-resistant acid phosphatase 5b (TRAP5b) which is a bone resorption marker. OPG and sclerostin were analysed using manual ELISA by Biomedica (Vienna, Austria). Trans-iliac bone biopsy was performed after tetracycline labelling. Bone samples were analysed using quantitative histomorphometry. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18 - 38µm3/µm2/year. Spearman rank correlation was used to test the relationship between the variables. Results Median BFR/BS was 32.12 (IQR 17.76 – 48.25) um3/um2/year. 26% of patients had low and 40% had high bone turnover. iPTH and OPG were positively correlated with BFR/BS (rho = 0.42, p&lt;0.01 and rho = 0.36, p&lt;0.05 respectively). Sclerostin was not correlated with BFR/BS. Furthermore, sclerostin did not correlate with bALP and intact PINP whereas OPG correlated with TRAP5b (rho = 0.43, p&lt;0.01). iPTH correlated with bALP (rho = 0.62, p&lt;0.001), intact PINP (rho = 0.62, p&lt;0.001) and TRAP5b (rho = 0.50, p = 0.001). Conclusion Circulating levels of iPTH and OPG were modestly associated with bone turnover but sclerostin was not. There are likely to be bone regulators other than iPTH, OPG and sclerostin which regulate bone turnover in renal osteodystrophy.

scholarly journals Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation

2021 ◽  
Author(s):  
Satu M. Keronen ◽  
Leena A. L. Martola ◽  
Patrik Finne ◽  
Inari S. Burton ◽  
Xiaoyu F. Tong ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Bone Biopsy ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bone Biomarkers ◽  
High Turnover ◽  
High Bone Turnover ◽  
High Bone

AbstractBone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18–70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.

Comparison of Cellular Response to Anorganic Bone Matrix/Cell Binding Peptide and Allogenic Cranial Bone After Sinus Augmentation in Rhesus Monkeys

2011 ◽  
Vol 37 (2) ◽  
pp. 233-245 ◽  
Author(s):  
Ihab El-Madany ◽  
Hany Emam ◽  
Mohamed Sharawy
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Volume Fraction ◽  
Mesenchymal Cells ◽  
Cranial Bone ◽  
Nuclear Antigen ◽  
Cell Binding ◽  
Freeze Dried ◽  
Bone Biopsies ◽  
Over Time

Abstract This study compared cellular responses of maxillary sinuses after augmentation with anorganic bovine-derived hydroxyapatite matrix linked to the cell binding polypeptide P-15 (ABM/P-15) or PepGen P-15 and allogenic freeze-dried cranial bone slabs. Five adult Macaque fascicularis monkeys were used. On one side, the floor of the sinus was augmented with ABM/P-15, while the other side was augmented with 2 cranial bone slabs. Trephine bone biopsies were obtained 6, 12, and 24 weeks postgrafting. Animals were sacrificed 8 months after grafting. Soft X-ray microradiography was used to determine bone density. The volume fraction (Vv) of regenerated bone, the number of mesenchymal cells, and the numbers of proliferating cell nuclear antigen (PCNA)- and alkaline phosphatase–positive cells at different augmentation sites were measured and compared. Basal bone heights were calculated at surgery and compared with total heights of the augmented sinus floors 8 months postgrafting. Bone formation, number of mesenchymal cells, PCNA index, and alkaline phosphatase index were significantly higher for the ABM/P-15 side than for the allogenic bone–augmented side. Both sides ended with a significant increase in bone height. The PCNA index decreased significantly over time (P &lt; .05), while the alkaline phosphatase index increased significantly (P &lt; .05) over time on both sides. Both graft materials have led to significant augmentation of the floor of the maxillary sinus with new bone; however, new bone formation and maturation were faster on the ABM/P-15 sites.

scholarly journals The effect of hormone replacement therapy on the expression of the alkaline phosphatase gene (ALPL) within the mucosal epithelium of the cheek and in peripheral blood lymphocytes

2014 ◽  
Vol 27 (2) ◽  
pp. 92-96 ◽  
Author(s):  
Mansur Rahnama ◽  
Michal Lobacz ◽  
Anna Szyszkowska ◽  
Grzegorz Trybek ◽  
Maryla Kozicka-Czupkallo
Keyword(s):  
Alkaline Phosphatase ◽  
Hormone Replacement Therapy ◽  
Bone Formation ◽  
Replacement Therapy ◽  
Peripheral Blood ◽  
Bone Mineralization ◽  
Hormone Replacement ◽  
Peripheral Blood Lymphocytes ◽  
Mucosal Epithelium ◽  
Osteoblast Activity

Abstract In adult life, proper bone metabolism requires efficient regulation of bone formation and resorption processes. Bone turnover markers allow for assessing the rate of bone formation and resorption processes. In menopausal period, female patients experience gradual reduction in blood estradiol levels. The deficit of estrogens leads to enhanced osteoclastogenesis and bone resorption. Alkaline phosphatase (ALP) is a membranebound enzyme that stimulates the osteoblast activity and bone mineralization. It is synthesized by osteoblasts and incorporated into the newly formed bone tissue. The produced enzyme stimulates the osteoblast activity and bone mineralization. The goal of this study is to determine the effect of hormone replacement therapy in postmenopausal women on the expression of alkaline phosphatase gene (ALPL) within the mucosal epithelium of the cheek and in peripheral blood lymphocytes. The studies show that hormone replacement therapy has no significant effect on the increase in ALPL expression within the mucosal epithelium of the cheek. Only in women having undergone ovarectomy (OV), the epithelial ALPL expression level was higher than in the remaining groups.

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

2020 ◽  
Vol 11 (3) ◽  
pp. 140-147
Author(s):  
Kalahasthi Ravibabu ◽  
Tapu Barman ◽  
Bhavani Shankara Bagepally
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Lead Battery ◽  
Exposed Workers ◽  
Tracp 5B ◽  
Battery Workers ◽  
Bone Turnover Biomarkers

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.

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