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Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is a common, chronic, progressive, and multifactorial musculoskeletal system disease affecting millions of people around the world. Despite the use of several treatment modalities, the search for a disease modifying drug continuous. Recent evidence suggest involvement of C-type natriuretic peptide (CNP) signaling in induction of chondroprotective pathways. A CNP analog (BMN 111) with an extended plasma half-life due to its neutral-endopeptidase resistance has shown to be pharmacologically active in achondroplasia enabling to hypothesize that BMN 111 may also be used as a treatment strategy in OA, in which CNP signaling has been suggested to be protective and/or reparative.

SUBMITTER: Tufan AC

PROVIDER: S-EPMC6818356 | biostudies-literature | 2019 Nov-Dec

REPOSITORIES: biostudies-literature

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Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

Tufan Ahmet Cevik AC

Journal of orthopaedics 20190525 6

Osteoarthritis (OA) is a common, chronic, progressive, and multifactorial musculoskeletal system disease affecting millions of people around the world. Despite the use of several treatment modalities, the search for a disease modifying drug continuous. Recent evidence suggest involvement of C-type natriuretic peptide (CNP) signaling in induction of chondroprotective pathways. A CNP analog (BMN 111) with an extended plasma half-life due to its neutral-endopeptidase resistance has shown to be phar ...[more]

PMID: 31680745

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Project description:BackgroundMinimal clinically important change (MCIC) represents the minimum patient-perceived improvement in an outcome after treatment, in an individual or within a group over time. This study aimed to determine MCIC of knee flexion in people with knee OA after non-surgical interventions using a meta-analytical approach.MethodsFour databases (MEDLINE, Cochrane, Web of Science and CINAHL) were searched for studies of randomised clinical trials of non-surgical interventions with intervention duration of ≤ 3 months that reported change in (Δ) (mean change between baseline and immediately after the intervention) knee flexion with Δ pain or Δ function measured using tools that have established MCIC values. The risk of bias in the included studies was assessed using version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Bayesian meta-analytic models were used to determine relationships between Δ flexion with Δ pain and Δ function after non-surgical interventions and MCIC of knee flexion.ResultsSeventy-two studies (k = 72, n = 5174) were eligible. Meta-analyses included 140 intervention arms (k = 61, n = 4516) that reported Δ flexion with Δ pain using the visual analog scale (pain-VAS) and Δ function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (function-WOMAC). Linear relationships between Δ pain at rest-VAS (0-100 mm) with Δ flexion were - 0.29 (- 0.44; - 0.15) (β: posterior median (CrI: credible interval)). Relationships between Δ pain during activity VAS and Δ flexion were - 0.29 (- 0.41, - 0.18), and Δ pain-general VAS and Δ flexion were - 0.33 (- 0.42, - 0.23). The relationship between Δ function-WOMAC (out of 100) and Δ flexion was - 0.15 (- 0.25, - 0.07). Increased Δ flexion was associated with decreased Δ pain-VAS and increased Δ function-WOMAC. The point estimates for MCIC of knee flexion ranged from 3.8 to 6.4°.ConclusionsThe estimated knee flexion MCIC values from this study are the first to be reported using a novel meta-analytical method. The novel meta-analytical method may be useful to estimate MCIC for other measures where anchor questions are problematic.Systematic review registrationPROSPERO CRD42022323927.

Project description:ObjectivesThis study was conducted to determine whether urinary excretion of C-type natriuretic peptide (CNP) is elevated in acute decompensated heart failure (ADHF) and whether elevated levels predict adverse outcomes.BackgroundUrinary CNP has been detected in patients with heart failure, but its clinical significance and prognostic utility, compared to established kidney injury biomarkers, in ADHF is unknown.MethodsWe measured 24-h urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients and 20 healthy control subjects. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase–associated lipocalin (NGAL) and plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) were also measured. Mortality and all-cause rehospitalization/death were assessed over a follow-up of 1.5 ± 0.9 years.ResultsADHF patients had higher urinary excretion of all 3 CNP molecular forms than did controls. Plasma CNP22 and CNP53 were elevated in ADHF but showed limited correlation with urinary excretion, suggesting that mainly renal-derived CNP appears in urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF (p < 0.0001); urinary NGAL was similar to that in controls. At 6 months, event-free survival values in ADHF patients were 86% for mortality and 59% for all-cause rehospitalization/death. On Cox regression analysis, urinary NT-CNP53 was the only predictor of mortality (hazard ratio: 1.7; 95% confidence interval: 1.1 to 2.4; p = 0.01) and all-cause rehospitalization/death (hazard ratio: 1.8; 95% confidence interval: 1.3 to 2.4; p = 0.0004), even after adjustment. Integrated discrimination analysis suggested that urinary NT-CNP53 combined with plasma NT-proBNP improved the prediction of adverse outcomes.ConclusionsThe findings from this study support the clinical utility of urinary CNP molecular forms. In ADHF, urinary NT-CNP53 correlated with prognosis, better predicted outcomes than did urinary NGAL and KIM-1, and improved the prognostic value of plasma NT-proBNP.

Dataset Information

Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

Publications

Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

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