scholarly journals BIOCHEMICAL MARKERS OF BONE RESORPTION, REGULATION OF OSTEOCLASTOGENESIS AND BONE LOSS FOLLOWING LIVER TRANSPLANTATION

2013 ◽  
Vol 16 (1) ◽  
pp. 18-23
Author(s):  
V P Buzulina ◽  
I A Pronchenko ◽  
I P Ermakova ◽  
N P Shmerko ◽  
A A Andrianova ◽  
...  

Methods and results: bone densitometry of L2-L4 and neck of femur, the level in serum of blood some hormones (PTH, vitamin D3, estradiol, testosterone) and cytokines (OPG, IL-6, FNO-a) regulating osteoclastogenesis as well as comparative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b) were fulfilled at different periods following orthotopic liver transplantation. At the early date after operation there were the bone density decrease of L2-L4, the lowering of vitamin D3, estradiol in women, testosterone in men and the elevation of cytokines and of resorption markers. In 1 and 2 years following liver transplantation there were revealed the rise of bone density, the level of PTH, estradiol, testosterone, which were associated with the lowering of IL-6, FNO-a and β-crosslaps while the level of vitamin D3 and TRAP-5b remained stable. Conclusion: at the early date TRAP-5b was more specific marker of bone resorption which did not depend on collagen metabolism in liver. In 1 and 2 years following liver transplantation bone resorbtion was association with level of PTH, FNO-a and OPG.

1995 ◽  
Vol 41 (11) ◽  
pp. 1592-1598 ◽  
Author(s):  
A Blumsohn ◽  
K E Naylor ◽  
A M Assiri ◽  
R Eastell

Abstract We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.


2019 ◽  
Vol 106 (2) ◽  
pp. 194-207 ◽  
Author(s):  
Laia Mira-Pascual ◽  
Christina Patlaka ◽  
Suchita Desai ◽  
Staffan Paulie ◽  
Tuomas Näreoja ◽  
...  

Abstract Tartrate-resistant acid phosphatase type 5 (TRAP) exists as two isoforms, 5a and 5b. 5b is a marker of osteoclast number and 5a of chronic inflammation; however, its association with bone resorption is unknown. In this study, a double-TRAP 5a/5b sandwich ELISA measuring 5a and 5b protein in the same sample was developed. TRAP 5a and 5b protein levels were evaluated as osteoclast differentiation/activity markers in serum and in culture, and their correlation to the resorption marker CTX-I was examined. Serum TRAP 5a and 5b concentrations in healthy men were 4.4 ± 0.6 ng/ml and 1.3 ± 0.2 ng/ml, respectively, and they correlated moderately to each other suggesting that their secretion is coupled under healthy conditions. A correlation was also observed between serum TRAP 5a and 5b with CTX-I, suggesting that both TRAP isoforms associate with osteoclast number. During osteoclast differentiation on plastic/bone, predominantly 5b increased in media/lysate from M-CSF/RANKL-stimulated CD14+ PBMCs. However, substantial levels of 5a were detected at later stages suggesting that both isoforms are secreted from differentiating OCs. More TRAP 5b was released on bone indicating a connection to osteoclast resorptive activity, and a peak in TRAP 5b/5a-ratio coincided with rapid CTX-I release. At the end of the culture period of M-CSF + RANKL-stimulated CD14+ PBMCs, there was a correlation between the secretion of TRAP 5a and 5b proteins with CTX-I. The correlation of not only 5b but also 5a with collagen degradation, both in serum and osteoclast cultures indicates that a considerable proportion of the TRAP 5a originates from osteoclasts and may reflect a hitherto undisclosed regulatory mechanism during bone resorption and bone remodeling.


Author(s):  
Christina Patlaka ◽  
Bojan Tubic ◽  
Pernilla Lång ◽  
Staffan Paulie ◽  
Diana Swolin-Eide ◽  
...  

Abstract Aim Tartrate-resistant acid phosphatase (TRAP) exists as isoforms 5a and 5b. TRAP 5a is a biomarker of chronic inflammation and influences adipose tissue and 5b associates with bone metabolism/pathologies. The aim was to investigate the association of serum TRAP 5a/5b isoforms with fat and bone markers and anthropometric parameters in patients with anorexia nervosa (AN) during weight gain therapy. Methods Twenty-five Swedish female AN patients, age 16–24 years, were treated for 12 weeks with a high-energy diet with six meals daily. Serum TRAP 5a/5b, markers of fat/glucose metabolism, markers of bone resorption and formation were measured. Parameters of bone and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Results BMI increased from median 15.4 kg/m2 to 19.0 kg/m2, p < 0.0001. TRAP 5a and 5a/5b ratio increased but TRAP 5b decreased during the study. TRAP Δ5a and Δ5b correlated with Δinsulin and Δadiponectin, respectively. TRAP 5b correlated with trabecular density at start but not at week 12. At 12 weeks, TRAP 5b correlated with CTX, and Δ decrease in TRAP 5b correlated to Δ increase in bone-specific alkaline phosphatase. Conclusions This clinical interventional study resulted in increased BMI in patients with AN. The decreased TRAP 5b protein levels confirm a role for TRAP 5b as a marker of bone resorption, whereas increased TRAP 5a seemed to derive from systemic changes in bone as well as metabolic changes. The combined detection of TRAP 5a and TRAP 5b in serum could be an indicator of improved bone metabolism. Level of evidence Level III, prospective interventional cohort study.


2019 ◽  
Vol 20 (20) ◽  
pp. 5196 ◽  
Author(s):  
Zhihao Chen ◽  
Eunjin Cho ◽  
Jinkyung Lee ◽  
Sunwoo Lee ◽  
Tae-Hoon Lee

Osteoclasts are poly-nuclear cells that resorb mineral components from old or damaged bone tissue. Primary mononuclear cells are activated by receptor activator of nuclear factor kappa-Β ligand (RANKL) and differentiate into large multinucleated cells. Dysregulation of osteoclast differentiation can lead to pathological bone loss and destruction. Many studies have focused on the development of new molecules to regulate RANKL-mediated signaling. In this study, N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(2-chlorophenoxy) acetamide (PPOA-N-Ac-2-Cl) led to a significant decrease in the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells in a dose-dependent manner, without inducing significant cytotoxicity. PPOA-N-Ac-2-Cl affected the expression of osteoclast-specific marker genes, such as TRAF6, c-fos, DC-STAMP, NFATc1, MMP9, CtsK, and TRAP (Acp5), during RANKL-mediated osteoclastogenesis. Moreover, PPOA-N-Ac-2-Cl significantly attenuated the protein levels of CtsK, a critical protease involved in bone resorption. Accordingly, bone resorption activity and F-actin ring formation decreased in the presence of PPOA-N-Ac-2-Cl. In conclusion, this study shows that PPOA-N-Ac-2-Cl acts as an inhibitor of osteoclast differentiation and may serve as a potential candidate agent for the treatment of osteoclast-related bone diseases by virtue of attenuating bone resorption.


Author(s):  
N. Safonov ◽  
O. Drobotun ◽  
E. Tuz ◽  
V. Vovk ◽  
N. Kolotilov

The purpose of the investigation is to study biochemical markers of bone metabolism in patients with breast cancer and prostate cancer during periods of stable remission and recurrence/metastasis and to assess their informative value in the diagnosis and monitoring of skeletal lesions. The study included 21 female patients with breast cancer and 18 male patients with prostate cancer. The start of monitoring is at least 3 years after complete tumor regression as a result of treatment: breast cancer – radical mastectomy, prostate cancer – radical prostatectomy. Markers of bone resorption (urine deoxypyridinoline, C-terminal telopeptide and tartrate-resistant acid phosphatase of blood serum) and osteogenesis (bone alkaline phosphatase and osteocalcin of blood serum) in patients with breast cancer and prostate cancer can be used for early diagnosis of metastasis in the skeleton bones: changes in indicators are observed 6-10 months before the first radiological/ MRI signs appear. The application of simultaneously used markers of bone resorption and osteogenesis in patients with breast cancer and prostate cancer provides a sensitivity of 89.7 %, a specificity of 84.5 %, a positive predictive value of 82.6 % and a negative predictive value of 95.3 %.


2021 ◽  
Vol 12 (1) ◽  
pp. 6-13
Author(s):  
L. V. Vasilyeva ◽  
E. N. Bezzubtseva ◽  
E. V. Gosteva ◽  
E. F. Evstratova

Osteoporosis is a progressive multifactorial systemic disease of the skeletal system characterized by the damage of the microarchitectonics of the bone tissue, which leads to the occurrence of low-energy fractures and impairment of the quality of life of individuals. The risk factors for the development of osteoporosis include smoking, which inhibits calcium absorption in the intestine and not only contributes to the reduction of bone density but also acts as a predictor of bronchopulmonary pathology. The systemic inflammation that develops in patients with chronic obstructive pulmonary disease, associated with the production of interleukins (IL)-6, IL-1, IL-8, and tumor necrosis factor – α, stimulates osteoclast-mediated bone resorption and a low level of osteoprotegerin closes the circle. In clinical practice, the determination of markers of bone resorption is required. This is a tartrate-resistant acid phosphatase, the 5β fraction of which signals the end of the resorption process; these are hydroxypyridine crosslinks – pyridoline (PYD) and deoxypyridoline, that stabilize the bone collagen molecule. Genetic factors also play an important role in the development of osteoporosis. The presence of the GG genotype or the G allele of the 283 A> G polymorphism (Bsml) of the VDR gene is a predictor of osteoporosis of the lumbar vertebrae L1-L4. The substitution of cytosine for thymine (C> T) in exon 17 of the calcitonin gene (CALCR) at position 1340 leads to the substitution of the amino acid proline (CCG) for leucine (CTG) at position 463 of the receptor protein molecule and affects bone density. But the most phylogenetically ancient mechanism for regulating the development and maintenance of tissue homeostasis by controlling cell proliferation, differentiation, migration, and apoptosis is the Wnt signaling pathway (SP-Wnt). Alterations in Wnt signaling observed in cases of genetic mutations cause various diseases of the human skeleton. A systematic literature search was carried out using the Scopus, PubMed, Web of Science databases.


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2985
Author(s):  
George Moschonis ◽  
Ellen GHM van den Heuvel ◽  
Christina Mavrogianni ◽  
Yannis Manios

Considering the role of bone metabolism in understanding the pathogenesis of osteoporosis, the aim of the present study was to examine the effects of vitamin D-enriched cheese on the serum concentrations of the parathyroid hormone (PTH) and certain bone remodeling biomarkers in postmenopausal women in Greece. In a randomised, controlled dietary intervention, 79 postmenopausal women (55–75 years old) were randomly allocated either to a control (CG: n = 39) or an intervention group (IG: n = 40), consuming 60 g of either non-enriched or vitamin D3-enriched Gouda-type cheese (5.7 μg of vitamin D3), respectively, daily and for eight weeks during the winter. The serum concentrations of 25-hydroxy vitamin D (25(OH)D), PTH, bone formation (i.e., osteocalcin, P1NP) and bone resorption (i.e., TRAP-5b) biomarkers were measured. Consumption of the vitamin D-enriched cheese led to higher serum 25(OH)D concentrations of 23.4 ± 6.39 (p = 0.022) and 13.4 ± 1.35 (p < 0.001) nmol/L in vitamin D-insufficient women being at menopause for less and more than 5 years, respectively. In vitamin D-insufficient women that were less than 5 years at menopause, consumption of vitamin D-enriched cheese was also associated with lower serum PTH (Beta −0.63 ± 1.11; p < 0.001) and TRAP-5b (Beta −0.65 ± 0.23; p = 0.004) levels at follow-up, compared with the CG. The present study showed that daily intake of 5.7 μg of vitamin D through enriched cheese increased serum 25(OH)D concentrations, prevented PTH increase and reduced bone resorption in vitamin D-insufficient early postmenopausal women, thus reflecting a food-based solution for reducing osteoporosis risk in this susceptible group.


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