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Nanoscale mechanisms in age-related hip-fractures.

ABSTRACT: Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano- and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups (n?=?10 each): ageing non-fractured donors (Controls); untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated). Collagen fibril, mineral and tissue mechanics were measured using synchrotron X-Ray diffraction of bone sections under load. Mechanical data were compared across groups, and tissue-level data were regressed against nano. Compared to controls fracture patients exhibited significantly lower critical tissue strain, max strain and normalized strength, with lower peak fibril and mineral strain. Bisphosphonate-treated exhibited the lowest properties. In all three groups, peak mineral strain coincided with maximum tissue strength (i.e. ultimate stress), whilst peak fibril strain occurred afterwards (i.e. higher tissue strain). Tissue strain and strength were positively and strongly correlated with peak fibril and mineral strains. Age-related fractures were associated with lower peak fibril and mineral strain irrespective of treatment. Indicating earlier mineral disengagement and the subsequent onset of fibril sliding is one of the key mechanisms leading to fracture. Treatments for fragility should target collagen-mineral interactions to restore nano-scale strain to that of healthy bone.

SUBMITTER: Ma S

PROVIDER: S-EPMC7450077 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Nanoscale mechanisms in age-related hip-fractures.

Ma Shaocheng S Goh En Lin EL Tay Tabitha T Wiles Crispin C CC Boughton Oliver O Churchwell John H JH Wu Yong Y Karunaratne Angelo A Bhattacharya Rajarshi R Terrill Nick N Cobb Justin P JP Hansen Ulrich U Abel Richard L RL

Scientific reports 20200826 1

Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano- and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups (n = 10 each): ageing non-fractured donors (Controls); untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated). Collagen fibril, mineral and tissue mechani ...[more]

PMID: 32848149

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Project description:BackgroundThis study aimed at investigating the characteristics of clinical trials related to hip fractures that were registered at ClinicalTrials.gov. It also aimed to identify potential risk factors associated with completion.Main bodyWe obtained 733 clinical studies related to hip fractures from the ClinicalTrials.gov database and included 470 studies in the analysis. These clinical trials were divided into behavioral, drug/biological, device, procedure, and other categories based on intervention types. Clinical trials investigating drugs or biologics were categorized based on the specific agents administered in each trial. Multiple logistic and Cox regression models were used to test the ability of 24 potential risk factors in predicting recruitment status and completion time, respectively. Among the included clinical trials, 44.89% (211/470) had complete recruitment status. The overall median completion time was 931.00 days (95% confidence interval [CI]: 822.56-1039.44 days). The results of only 8.94% (42/470) of clinical trials were presented on the ClinicalTrials.gov website. Bupivacaine (a local anesthetic) was most commonly investigated (in 25 clinical trials); this was followed by ropivacaine (another local anesthetic, 23 clinical trials) and tranexamic acid (a hemostatic, 21 clinical trials). Multivariate analysis showed that trials including children (P = 0.03) and having National Institutes of Health funds (P < 0.01) had significantly higher rates of complete recruitment. Higher enrollment (P < 0.01), National Institutes of Health funding (P < 0.01), location in the United States (P = 0.04), and location in Europe (P = 0.03) predisposed to longer completion time, while studies involving drugs/biologics (P < 0.01) had shorter completion times.ConclusionsA considerable proportion of clinical trials related to hip fractures were completed, but the results of only a small fraction were presented on the ClinicalTrials.gov website. The commonly investigated drugs focused on anesthesia, pain relief, and hemostasis. Several independent risk factors that affect recruitment status and completion time were identified. These factors may guide the design of clinical trials relating to hip fractures.

Project description:BackgroundVarious nerve blocks with local anaesthetic agents have been used to reduce pain after hip fracture and subsequent surgery. This review was published originally in 1999 and was updated in 2001, 2002, 2009 and 2017.ObjectivesThis review focuses on the use of peripheral nerves blocks as preoperative analgesia, as postoperative analgesia or as a supplement to general anaesthesia for hip fracture surgery. We undertook the update to look for new studies and to update the methods to reflect Cochrane standards.Search methodsFor the updated review, we searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE (Ovid SP, 1966 to August week 1 2016), Embase (Ovid SP, 1988 to 2016 August week 1) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to August week 1 2016), as well as trial registers and reference lists of relevant articles.Selection criteriaWe included randomized controlled trials (RCTs) involving use of nerve blocks as part of the care provided for adults aged 16 years and older with hip fracture.Data collection and analysisTwo review authors independently assessed new trials for inclusion, determined trial quality using the Cochrane tool and extracted data. When appropriate, we pooled results of outcome measures. We rated the quality of evidence according to the GRADE Working Group approach.Main resultsWe included 31 trials (1760 participants; 897 randomized to peripheral nerve blocks and 863 to no regional blockade). Results of eight trials with 373 participants show that peripheral nerve blocks reduced pain on movement within 30 minutes of block placement (standardized mean difference (SMD) -1.41, 95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0 to 10; I2 = 90%; high quality of evidence). Effect size was proportionate to the concentration of local anaesthetic used (P < 0.00001). Based on seven trials with 676 participants, we did not find a difference in the risk of acute confusional state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I2 = 48%; very low quality of evidence). Three trials with 131 participants reported decreased risk for pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I2 = 3%; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of evidence). We did not find a difference in risk of myocardial ischaemia or death within six months, but the number of participants included was well below the optimal information size for these two outcomes. Two trials with 155 participants reported that peripheral nerve blocks also reduced time to first mobilization after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I2 = 52%; moderate quality of evidence). One trial with 75 participants indicated that the cost of analgesic drugs was lower when they were given as a single shot block (SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence).Authors' conclusionsHigh-quality evidence shows that regional blockade reduces pain on movement within 30 minutes after block placement. Moderate-quality evidence shows reduced risk for pneumonia, decreased time to first mobilization and cost reduction of the analgesic regimen (single shot blocks).

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Nanoscale mechanisms in age-related hip-fractures.

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Nanoscale mechanisms in age-related hip-fractures.

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