CCL5 (RANTES) Is Suspected to Be the Key Chemokine to Understand the Bone Pathology of Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5150-5150
Author(s):  
Kunio Hayashi ◽  
Shosaku Nomura ◽  
Seiji Hashimoto ◽  
Teru Hideshima
Keyword(s):  
Healthy Volunteers ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Newly Diagnosed ◽  
Bone Pathology ◽  
Male And Female ◽  
Weekly Cycle ◽  
Treatment Regimens ◽  
Stage 1

Abstract Background: It has been shown that CCL5 recruits Osteoclasts and Osteoblasts to active bone turnover regions to maintain bone remodeling. In healthy volunteers, CCL5 is higher in male than in female. Although CCL5 is highest in 20ys men, it becomes same level at 60ys in both male and female. These results suggest that the value of CCL5 correlates with the activity of the bone metabolism. In this study, we examined the significance of CCL5 level in MM, which may provide new insights in the bone pathology of this disease. Patients and Methods: fourteen MM were enrolled in our study. Twelve were newly diagnosed and 2 were relapsed patients. We evaluated CCL5(serum) and bone alkaline phosphatase(BAP, serum), as well as type-I collagen N-telopeptide(NTX, urine) when patients were diagnosed and after the treatment. Regimens of the treatment are Thalidomide 200mg/day and Dexamethasone(Dex) 40mg every 8th day within 21 days cycle, Velcade 1.3mg/m2 on days 1, 4, 8, 11 of a 3 weekly cycle with Dex 40mg, combination of Thalidomide, Velcade and Dex. Result: We compare CCL5 of 60ys healthy volunteers, ITP patients, Stage 1 MM, Stage2 MM and Stage3 MM. We found highest CCL5 level in Stage 3 MM. Interestingly, BAP was almost same level between Stage1 and Stage3; however NTX level is higher in Stage3 than in Stage1, suggesting that increased CCL5 in Stage3 was predominantly from activated osteoclasts. Importantly increased CCL5 and BAP were recognized in patients who had CR or PR. Moreover, the increase of the number of megakaryocyts in the bone marrow was recognized in 7 patients. These megakaryocytes were strongly stained with anti-CCL5 Ab, suggesting that successful MM treatments could increase production of CCL5 by megakaryocytes. Conclusion: CCL5 of Osteoclasts in active myeloma contributes bone resorption. On the other hand, in successfuly treated myeloma, CCL5 is produced by megakaryocytes which make Osteoblasts activate. CCL5 may be a novel marker of bone disease in myeloma.

scholarly journals Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain

1998 ◽  
Vol 44 (8) ◽  
pp. 1621-1628 ◽  
Author(s):  
Per Magnusson ◽  
Lasse Larsson ◽  
Gunnar Englund ◽  
Brita Larsson ◽  
Peter Strang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Type I Collagen ◽  
Specific Antigen ◽  
Bone Alkaline Phosphatase ◽  
The Body ◽  
Skeletal Metastases ◽  
Type I ◽  
Apparent Difference ◽  
Hormone Refractory ◽  
Healthy Males

Abstract We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.

scholarly journals Space Flight Is Associated with Rapid Decreases of Undercarboxylated Osteocalcin and Increases of Markers of Bone Resorption without Changes in Their Circadian Variation: Observations in Two Cosmonauts

2000 ◽  
Vol 46 (8) ◽  
pp. 1136-1143 ◽  
Author(s):  
Anne Caillot-Augusseau ◽  
Laurence Vico ◽  
Martina Heer ◽  
Dimitri Voroviev ◽  
Jean-Claude Souberbielle ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Remodeling ◽  
Vitamin K ◽  
Space Flight ◽  
Type I Collagen ◽  
Circadian Variation ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Undercarboxylated Osteocalcin ◽  
Type I Procollagen

Abstract Background: Microgravity induces bone loss by mechanism(s) that remain largely unknown. Methods: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. Results: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. Conclusion: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

scholarly journals Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kuo-Chin Hung ◽  
Chung-Yu Huang ◽  
Chuan-Chieh Liu ◽  
Chih-Jen Wu ◽  
Shao-Yuan Chen ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Bone Resorption ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Resorption Markers ◽  
Correlation Analyses ◽  
Serum Trap ◽  
The Cross

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n=23) or who did not develop refractory SHPT (control subjects;n=25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

scholarly journals Serum Concentrations of Cross-Linked N-Telopeptides of Type I Collagen: New Marker for Bone Resorption in Hemodialysis Patients

2005 ◽  
Vol 51 (12) ◽  
pp. 2312-2317 ◽  
Author(s):  
Yoshifumi Maeno ◽  
Masaaki Inaba ◽  
Senji Okuno ◽  
Tomoyuki Yamakawa ◽  
Eiji Ishimura ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Bone Resorption Marker ◽  
Type I ◽  
Serum Concentrations ◽  
Mineral Density ◽  
Intact Osteocalcin ◽  
Bone Formation Markers

Abstract Background: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). Methods: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (β-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient’s bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. Results: Serum NTX correlated significantly with β-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as β-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, β-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. Conclusion: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

scholarly journals Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Yue-Yue Huang ◽  
Zi-Hao Wang ◽  
Li-Hui Deng ◽  
Hong Wang ◽  
Qun Zheng
Keyword(s):  
Animal Model ◽  
Oral Administration ◽  
Type I Collagen ◽  
Maximum Load ◽  
Type I ◽  
Bone Pathology ◽  
Treatment Of Osteoporosis ◽  
Beneficial Effects ◽  
Existing Problems ◽  
Item Checklist

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen ( P < 0.05 ). No statistical difference was seen in survival rate, index of liver, or kidney function ( P > 0.05 ). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.

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