Urinary markers of bone resorption, pyridinoline and deoxypyridinoline, are increased in sickle cell patients with further increments during painful crisis

Nur, Erfan; Mairuhu, Willem M.; Biemond, Bart J.; Zanten, Anton P. van; Schnog, John‐John B.; Brandjes, Dees P. M.; Otten, Hans-Martin

doi:10.1002/ajh.21856

Cited by 16 publications

(9 citation statements)

References 31 publications

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“…Limited studies on SBD are available and its pathogenesis has been only partially investigated. 18,[43][44][45][46][47] Here we show bone impairment and bone loss in SCD mice under normoxic conditions. This was associated with downregulation of osteogenic markers (Runx2 and Sparc) and increased osteoclast activity (RankL) without major changes in osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 58%

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Carbonare

Mattè

Valenti

et al. 2015

Blood

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Key Points• In SCD, recurrent vasoocclusive crisis suppresses osteogenic lineage and activates osteoclasts.• Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/ osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD. (Blood. 2015;126(20):2320-2328 IntroductionSickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75 000 individuals in the United States and almost 20 000 to 25 000 individuals in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharan Africa to European countries.1-3 Studies of the global burden of disease have pointed out the invalidating impact of SCD on patient quality of life.2 This requires the development of new therapeutic options to treat sickle cell-related acute and chronic complications.SCD is caused by a point mutation in the b-globin gene resulting in the synthesis of pathologic hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density, and further acceleration of HbS polymerization. [4][5][6] Pathophysiologic studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of ...

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Section: Discussionmentioning

confidence: 58%

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Carbonare

Mattè

Valenti

et al. 2015

Blood

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“…Hydroxyproline and glucosamine, normally excreted through urine, indicate the excess breakdown of ECM during progression of arthritis24. Pyridinoline and deoxypyridinoline are excreted unmetabolized in urine and were also recognised as the markers of the bone resorbtion and osteoclast activity during bone and joint disease25. In the present study, quantification of increased level of urinary hydroxyproline, glucosamine, pyridinoline and deoxypyridinoline, indicated the breakdown of collagen matrix during the onset of OA in arthritic control rats, which was restored after GNP-NKCT1 treatment.…”

Section: Discussionmentioning

confidence: 99%

Protection against osteoarthritis in experimental animals by nanogold conjugated snake venom protein toxin gold nanoparticle-Naja kaouthia cytotoxin 1

Gomes

Saha

Bhowmik

et al. 2016

Indian Journal of Medical Research

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Background & objectives:Increased severity of osteoarthritis (OA) and adverse side effects of its treatment led to the search for alternative therapies. It was previously reported that snake venom protein toxin Naja kaouthia cytotoxin 1 (NKCT1) and gold nanoparticle (GNP) individually have potential against excremental arthritis. In this study, we analyzed the protective activity of GNP conjugated protein toxin NKCT1 (GNP-NKCT1) against experimental OA.Methods:Gold nanoparticle conjugation with NKCT1 (GNP-NKCT1) was done and its physiochemical properties were studied. OA was induced in male albino rats by intra-articular injection of bacterial collagenase and treatment was done with NKCT1/GNP-NKCT1/standard drug (indomethacin). Physical parameter (ankle diameter), urinary markers (hydroxyproline, glucosamine, pyridinoline, deoxypyridinoline), serum and synovial membrane pro-inflammatory markers [tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-17, vascular endothelial growth factor (VEGF)] and matrix metalloproteinase 1 (MMP1) were measured. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface were also done.Results:Physical parameters, urinary markers, serum and synovial membrane pro-inflammatory makers and MMP1 were increased in arthritic rats and significantly restored after GNP-NKCT1/NKCT1 treatment. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface also indicated the protective effect of GNP-NKCT1 against inflammatory response and cartilage degradation in osteoarthritic rats.Interpretation & conclusions:In this study restoration of the arthritic markers and bone degradation by GNP-NKCT1 treatment indicated the anti-osteoarthritic property of GNP-NKCT1. Further studies need to be done to confirm these findings.

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“…Pyridinoline and deoxypyridinoline are formed of cross‐linked collage fibres and are released into the blood during bone turnover. Urinary levels are raised in asymptomatic SCD, increasing further during episodes of acute pain (Nur et al , 2010). Other studies have similarly identified increased plasma or urine levels of many markers of bone turnover, including osteocalcin.…”

Section: Biomarkers Of Damage To Specific Organsmentioning

confidence: 99%

Biomarkers in sickle cell disease

2011

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More than 100 different blood and urine biomarkers have been described in sickle cell disease (SCD), with the number increasing rapidly as analytical techniques develop. Nearly all of these biomarkers are abnormal in the steady state, and become more so during complications. The range of abnormalities demonstrates the multisystem nature of SCD and the complex pathophysiology. Some biomarkers indicate damage to specific organs, such as urine albumin:creatinine ratio in nephropathy, whereas others indicate more systemic processes. Biomarkers have been useful in identifying various interrelated pathological mechanisms, including haemolysis, inflammation, hypercoagulability, oxidative stress, reperfusion injury, vasculopathy and endothelial dysfunction. However, most biomarkers correlate closely with other more routine measurements, and also with each other. It is not clear that any provide specific prognostic or clinical information beyond that given by the simple measurement of haemoglobin concentration. The identification of prognostically validated biomarkers in prospective clinical trials would be useful.

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Urinary markers of bone resorption, pyridinoline and deoxypyridinoline, are increased in sickle cell patients with further increments during painful crisis

Cited by 16 publications

References 31 publications

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Protection against osteoarthritis in experimental animals by nanogold conjugated snake venom protein toxin gold nanoparticle-Naja kaouthia cytotoxin 1

Biomarkers in sickle cell disease

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