High- Versus Low-Dose Exercise Therapy for Knee Osteoarthritis : A Randomized Controlled Multicenter Trial.

BACKGROUND: The benefits of exercise in patients with knee osteoarthritis are well documented, but the optimal exercise dose remains unknown. OBJECTIVE: To compare high-dose versus low-dose exercise therapy with regard to knee function, pain, and quality of life (QoL) in patients with long-term symptomatic knee osteoarthritis. DESIGN: A Swedish and Norwegian multicenter randomized controlled superiority trial with multiple follow-ups up to 12 months after the intervention. (ClinicalTrials.gov: NCT02024126). SETTING: Primary health care facilities. PATIENTS: 189 patients with diagnosed knee osteoarthritis and a history of pain and decreased knee function were assigned to high-dose therapy (n = 98; 11 exercises; 70 to 90 minutes) or low-dose therapy (n = 91; 5 exercises; 20 to 30 minutes). INTERVENTION: Patient-tailored exercise programs according to the principles of medical exercise therapy. Global (aerobic), semiglobal (multisegmental), and local (joint-specific) exercises were performed 3 times a week for 12 weeks under supervision of a physiotherapist. MEASUREMENTS: The Knee Injury and Osteoarthritis Outcome Score (KOOS) was measured biweekly during the 3-month intervention period and at 6 and 12 months after the intervention. The primary end point was the mean difference in KOOS scores between groups at the end of the intervention (3 months). Secondary outcomes included pain intensity and QoL. The proportion of patients with minimal clinically important changes in primary and secondary outcomes was compared between groups. RESULTS: Both groups improved over time, but there were no benefits of high-dose therapy in most comparisons. One exception was the KOOS score for function in sports and recreation, where high-dose therapy was superior at the end of treatment and at 6-month follow-up. A small benefit in QoL at 6 and 12 months was also observed. LIMITATION: There was no control group that did not exercise. CONCLUSION: The results do not support the superiority of high-dose exercise over low-dose exercise for most outcomes. However, small benefits with high-dose exercise were found for knee function in sports and recreation and for QoL. PRIMARY FUNDING SOURCE: Swedish Rheumatic Fund.

Summarizing the effects of different exercise types in chronic neck pain - a systematic review and meta-analysis of systematic reviews.

BACKGROUND: To date, no consensus exists as to whether one exercise type is more effective than another in chronic neck pain. This systematic review and meta-analysis of systematic reviews aimed to summarize the literature on the effect of various exercise types used in chronic neck pain and to assess the certainty of the evidence. METHODS: We searched the databases Ovid MEDLINE, Embase, Cochrane Library, SportDiscus, and Web of Science (Core Collection) for systematic reviews and meta-analyses on adults between 18 and 70 years with chronic neck pain lasting ≥ 12 weeks which investigated the effects of exercises on pain and disability. The included reviews were grouped into motor control exercise (MCE), Pilates exercises, resistance training, traditional Chinese exercise (TCE), and yoga. Study quality was assessed with AMSTAR-2 and the level of certainty for the effects of the exercise through GRADE. A narrative analysis of the results was performed and in addition, meta-analyses when feasible. RESULTS: Our database search resulted in 1,794 systematic reviews. We included 25 systematic reviews and meta-analyses including 17,321 participants (overlap not accounted for). The quality of the included reviews ranged from critically low to low (n = 13) to moderate to high (n = 12). We found low to high certainty of evidence that MCE, Pilates exercises, resistance training, TCE, and yoga have short-term positive effects on pain and that all exercise types except resistance training, show positive effects on disability compared to non-exercise controls. We found low to moderate certainty of evidence for conflicting results on pain and disability when the exercise types were compared to other exercise interventions in the short-term as well as in intermediate/long-term apart for yoga, as no long-term results were available. CONCLUSION: Overall, our findings show low to high certainty of evidence for positive effects on pain and disability of the various exercise types used in chronic neck pain compared to non-exercise interventions, at least in the short-term. Based on our results, no optimal exercise intervention for patients with chronic neck pain can be recommended, since no large differences between the exercise types were shown here. Because the quality of the included systematic reviews varied greatly, future systematic reviews need to increase their methodological quality. TRIAL REGISTRATION: Prospero CRD42022336014.

Summarizing the effects of different exercise types in chronic low back pain - a systematic review of systematic reviews.

BACKGROUND: In chronic LBP (CLBP), guideline-endorsed treatment is to stay active, return to normal activity, and to exercise. Several reviews on various exercise types used in CLBP have been published. We aimed to identify systematic reviews of common exercise types used in CLBP, to appraise their quality, and to summarize and compare their effect on pain and disability. METHODS: We searched the databases OVID MEDLINE, EMBASE, COCHRANE LIBRARY, and WEB OF SCIENCE (Core collection) for systematic reviews and meta-analyses on adults between 18 and 70 years of age suffering from chronic or recurrent LBP for a period of at least 12 weeks, which investigated the effects of exercises on pain and disability. All searches were conducted without language restriction. The search was performed up until 2022-01-26. The included reviews were grouped into nine exercise types: aerobic training, aquatic exercises, motor control exercises (MCE), resistance training, Pilates, sling exercises, traditional Chinese exercises (TCE), walking, and yoga. The study quality was assessed with AMSTAR-2. For each exercise type, a narrative analysis was performed, and the level of evidence for the effects of exercise was assessed through GRADE. RESULTS: Our database search resulted in 3,475 systematic reviews. Out of the 253 full texts that were screened, we included 45 systematic reviews and meta-analyses. The quality of the included reviews ranged from high to critically low. Due to large heterogeneity, no meta-analyses were performed. We found low-to-moderate evidence of mainly short-term and small beneficial effects on pain and disability for MCE, Pilates, resistance training, TCE, and yoga compared to no or minimal intervention. CONCLUSIONS: Our findings show that the effect of various exercise types used in CLBP on pain and disability varies with no major difference between exercise types. Many of the included systematic reviews were of low-to-moderate quality and based on randomized controlled trials with high risk of bias. The conflicting results seen, undermine the certainty of the results leading to very-low-to-moderate quality of evidence for our results. Future systematic reviews should be of higher quality to minimize waste of resources. TRIAL REGISTRATION: PROSPERO: Reg no 190409 Registration date 01AUG 2020.

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.

Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, and tissue turnover by degrading extracellular matrix (ECM) components and by releasing matrikines, cell surface-bound cytokines, growth factors, or their receptors. Among the MMPs, MMP-14 is the driving force behind extracellular matrix and tissue destruction during cancer invasion and metastasis. MMP-14 also influences both intercellular as well as cell-matrix communication by regulating the activity of many plasma membrane-anchored and extracellular proteins. Cancer cells and other cells of the tumor stroma, embedded in a common extracellular matrix, interact with their matrix by means of various adhesive structures, of which particularly invadopodia are capable to remodel the matrix through spatially and temporally finely tuned proteolysis. As a deeper understanding of the underlying functional mechanisms is beneficial for the development of new prognostic and predictive markers and for targeted therapies, this review examined the current knowledge of the interplay of the various MMPs in the cancer context on the protein, subcellular, and cellular level with a focus on MMP14.

Evaluation of carrier density and mobility in Mn ion-implanted GaAs:Zn nanowires by Raman spectroscopy.

The fabrication of complex nanoscale electronics with reduced dimensions poses challenges on novel techniques to accurately determine fundamental electronic parameters. In this article, we present a universal contactless method based on Raman scattering for measuring the mobility and hole concentration independently in GaAs:Zn and Mn ion-implanted GaAs:Zn nanowires, potentially of great interest for spintronics applications. Clear coupled longitudinal optical phonon-plasmon modes were recorded and fitted with a dielectric function, based on the Drude model, which includes contributions from both plasmons and phonons. From the fitting, we extract accurate values of the plasma frequency and plasma damping constant from which we directly calculate the hole density and mobility, respectively. The extracted mobilities were also used as input data for analysis of complementary four-probe transport measurements, where the corresponding hole concentrations could be calculated and found to be in good agreement with those extracted directly from the Raman data. We also investigated the influence of annealing of the GaAs:Zn nanowires on the hole concentration and mobility and found strong indications of thermally activated defects related to a formed crystalline As/oxide shell around the nanowires. The method proposed here is extremely powerful for the characterization of nanoelectronics in general, and nanospintronics in particular for which Hall measurements are difficult to pursue due to problems related to contact formation, as well as to inherent magnetic properties of the devices.

Raman characterization of single-crystalline Ga0.96Mn0.04As:Zn nanowires realized by ion-implantation.

Recent progress in the realization of magnetic GaAs nanowires (NWs) doped with Mn has attracted a lot of attention due to their potential application in spintronics. In this work, we present a detailed Raman investigation of the structural properties of Zn doped GaAs (GaAs:Zn) and Mn-implanted GaAs:Zn (Ga0.96Mn0.04As:Zn) NWs. A significant broadening and redshift of the optical TO and LO phonon modes are observed for these NWs compared to as-grown undoped wires, which is attributed to strain induced by the Zn/Mn doping and to the presence of implantation-related defects. Moreover, the LO phonon modes are strongly damped, which is interpreted in terms of a strong LO phonon-plasmon coupling, induced by the free hole concentration. Moreover, we report on two new interesting Raman phonon modes (191 and 252 cm-1) observed in Mn ion-implanted NWs, which we attribute to Eg (TO) and A1g (LO) vibrational modes in a sheet layer of crystalline arsenic present on the surface of the NWs. This conclusion is supported by fitting the observed Raman shifts for the SO phonon modes to a theoretical dispersion function for a GaAs NW capped with a dielectric shell.

Non-participation in initial and repeated health risk appraisals - a drop-out analysis based on a health project.

BACKGROUND: Health risk assessment (HRAs) are commonly used by occupational health services (OHS) to aid workplaces in keeping their employees healthy, but for unknown reasons, many employees choose not to participate in the HRAs. The aim of the study was to explore whether demographic, lifestyle and health-related factors in employees are associated with non-participation in initial and repeated HRAs. METHODS: In an OHS-based health project, 2022 municipal employees were asked to participate in three repeated HRAs. Multiple logistic regression analyses were used so as to determine associations between non-participating and demographic, lifestyle and health-related factors (e.g. biomarkers). RESULTS: Among the employees who were asked to participate in the health project, more than half did not participate in any HRA and among those who did, more than one third did not participate in repeated HRAs. Young age, male sex and being employed in the Technical department or Health and Social Care department in comparison with being employed in the department for Childcare and Education were factors significantly associated with non-participation in the initial HRA. These factors, together with being on sick leave and having unhealthy dietary habits, were factors associated with non-participation in repeated HRAs. CONCLUSIONS: Among the non-participators in initial HRAs and in repeated HRAs younger men and those already related to ill-health were overrepresented. This implicates that health care providers to a higher extent should focus on "those most needed" and that employers should be more engaged in results of repeated HRA's. Future studies should focus on modifiable variables that could make the HRAs more attractive and inclusive.

Reliability and validity of a novel Kinect-based software program for measuring posture, balance and side-bending.

BACKGROUND: Clinical examinations are subjective and often show a low validity and reliability. Objective and highly reliable quantitative assessments are available in laboratory settings using 3D motion analysis, but these systems are too expensive to use for simple clinical examinations. Qinematic™ is an interactive movement analyses system based on the Kinect camera and is an easy-to-use clinical measurement system for assessing posture, balance and side-bending. The aim of the study was to test the test-retest the reliability and construct validity of Qinematic™ in a healthy population, and to calculate the minimal clinical differences for the variables of interest. A further aim was to identify the discriminative validity of Qinematic™ in people with low-back pain (LBP). METHODS: We performed a test-retest reliability study (n = 37) with around 1 week between the occasions, a construct validity study (n = 30) in which Qinematic™ was tested against a 3D motion capture system, and a discriminative validity study, in which a group of people with LBP (n = 20) was compared to healthy controls (n = 17). We tested a large range of psychometric properties of 18 variables in three sections: posture (head and pelvic position, weight distribution), balance (sway area and velocity in single- and double-leg stance), and side-bending. RESULTS: The majority of the variables in the posture and balance sections, showed poor/fair reliability (ICC < 0.4) and poor/fair validity (Spearman <0.4), with significant differences between occasions, between Qinematic™ and the 3D-motion capture system. In the clinical study, Qinematic™ did not differ between people with LPB and healthy for these variables. For one variable, side-bending to the left, there was excellent reliability (ICC =0.898), excellent validity (r = 0.943), and Qinematic™ could differentiate between LPB and healthy individuals (p = 0.012). CONCLUSION: This paper shows that a novel software program (Qinematic™) based on the Kinect camera for measuring balance, posture and side-bending has poor psychometric properties, indicating that the variables on balance and posture should not be used for monitoring individual changes over time or in research. Future research on the dynamic tasks of Qinematic™ is warranted.

A novel fibrinolytic metalloproteinase, barnettlysin-I from Bothrops barnetti (Barnett´s pitviper) snake venom with anti-platelet properties.

BACKGROUND: Viperid snake venoms contain active components that interfere with hemostasis. We report a new P-I class snake venom metalloproteinase (SVMP), barnettlysin-I (Bar-I), isolated from the venom of Bothrops barnetti and evaluated its fibrinolytic and antithrombotic potential. METHODS: Bar-I was purified using a combination of molecular exclusion and cation-exchange chromatographies. We describe some biochemical features of Bar-I associated with its effects on hemostasis and platelet function. RESULTS: Bar-I is a 23.386 kDa single-chain polypeptide with pI of 6.7. Its sequence (202 residues) shows high homology to other members of the SVMPs. The enzymatic activity on dimethylcasein (DMC) is inhibited by metalloproteinase inhibitors e.g. EDTA, and by α2-macroglobulin. Bar-I degrades fibrin and fibrinogen dose- and time-dependently by cleaving their α-chains. Furthermore, it hydrolyses plasma fibronectin but not laminin nor collagen type I. In vitro Bar-I dissolves fibrin clots made either from purified fibrinogen or from whole blood. In contrast to many other P-I SVMPs, Bar-I is devoid of hemorrhagic activity. Also, Bar-I dose- and time-dependently inhibits aggregation of washed human platelets induced by vWF plus ristocetin and collagen (IC50=1.3 and 3.2 µM, respectively), presumably Bar-I cleaves both vWF and GPIb. Thus, it effectively inhibits vWF-induced platelet aggregation. Moreover, this proteinase cleaves the collagen-binding α2-A domain (160 kDa) of α2ß1-integrin. This explains why it additionally inhibits collagen-induced platelet activation. CONCLUSION: A non-hemorrhagic but fibrinolytic metalloproteinase dissolves fibrin clots in vitro and impairs platelet function. GENERAL SIGNIFICANCE: This study provides new opportunities for drug development of a fibrinolytic agent with antithrombotic effect.

CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo development of granzyme B-expressing regulatory B cells in HIV patients.

IL-21 can induce both plasma cells and regulatory B cells. In this article, we demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B. Granzyme B-expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10. The main functional characteristic of their regulatory activity is direct granzyme B-dependent degradation of the TCR-ζ-chain, resulting in significantly decreased proliferative T cell responses. Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L. When culturing such IL-21(+)CD40L(-) Th cells with B cells, the former directly induce B cell differentiation into GraB cells. In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21-dependent B cell differentiation. As proof of principle, we confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO mutation. The majority of peripheral B cells from this patient were GraB cells and strongly suppressed T cell proliferation. In conclusion, GraB cells represent potent regulatory B cells in humans that are phenotypically and functionally distinct from B10 cells and occur in early HIV infection. GraB cells may contribute significantly to immune dysfunction in HIV patients, and may also explain ineffective Ab responses after vaccination. The use of soluble CD40L multimers may help to improve vaccination responses in HIV patients.

Synthesis, Morphological, and Electro-optical Characterizations of Metal/Semiconductor Nanowire Heterostructures.

In this letter, we demonstrate the formation of unique Ga/GaAs/Si nanowire heterostructures, which were successfully implemented in nanoscale light-emitting devices with visible room temperature electroluminescence. Based on our recent approach for the integration of InAs/Si heterostructures into Si nanowires by ion implantation and flash lamp annealing, we developed a routine that has proven to be suitable for the monolithic integration of GaAs nanocrystallite segments into the core of silicon nanowires. The formation of a Ga segment adjacent to longer GaAs nanocrystallites resulted in Schottky-diode-like I/V characteristics with distinct electroluminescence originating from the GaAs nanocrystallite for the nanowire device operated in the reverse breakdown regime. The observed electroluminescence was ascribed to radiative band-to-band recombinations resulting in distinct emission peaks and a low contribution due to intraband transition, which were also observed under forward bias. Simulations of the obtained nanowire heterostructure confirmed the proposed impact ionization process responsible for hot carrier luminescence. This approach may enable a new route for on-chip photonic devices used for light emission or detection purposes.

Shaping and compositional modification of zinc oxide nanowires under energetic manganese ion irradiation.

For ZnO nanowires of 150 to 200 nm diameter standing on a flat substrate, the development of the surface contour/morphology and the local elemental composition under 175 keV Mn irradiation has been investigated both experimentally and by means of three-dimensional dynamic Monte Carlo computer simulation. The simulation results reveal a complex interplay of sputter erosion, implant incorporation, resputtering and atomic mixing, which is discussed in detail. The sputter-induced thinning of the wire is in good quantitative agreement with the experimental results obtained from pre- and post-irradiation scanning electron microscopy. The experiments also confirm the predicted sharpening of the tip, neck formation at the bottom interface, and ultimately the detachment of the nanowires from the substrate at high ion fluence. Additional good agreement with experimental results from nano-x-ray fluorescence is also obtained for the continuously increasing Mn/Zn atomic ratio within the nanowires as a function of ion fluence. The simulation yields a great deal of additional information that has not been accessible in the experiments. From this, preferential sputtering of O compared with Zn is deduced. A significant contamination of the wires with substrate material arises from ion mixing at the wire/substrate interface, rather than from redeposition of sputtered substrate atoms. Surprising hollow profiles are observed. Their formation is attributed to a special mechanism of collisional transport which is characteristic of the irradiation of nanowires at a suitable combination of wire diameter and ion energy.

Shape manipulation of ion irradiated Ag nanoparticles embedded in lithium niobate.

Spherical silver nanoparticles were prepared by means of ion beam synthesis in lithium niobate. The embedded nanoparticles were then irradiated with energetic (84)Kr and (197)Au ions, resulting in different electronic energy losses between 8.1 and 27.5 keV nm(-1) in the top layer of the samples. Due to the high electronic energy losses of the irradiating ions, molten ion tracks are formed inside the lithium niobate in which the elongated Ag nanoparticles are formed. This process is strongly dependent on the initial particle size and leads to a broad aspect ratio distribution. Extinction spectra of the samples feature the extinction maximum with shoulders on either side. While the maximum is caused by numerous remaining spherical nanoparticles, the shoulders can be attributed to elongated particles. The latter could be verified by COMSOL simulations. The extinction spectra are thus a superposition of the spectra of all individual particles.

Anomalous Plastic Deformation and Sputtering of Ion Irradiated Silicon Nanowires.

Silicon nanowires of various diameters were irradiated with 100 keV and 300 keV Ar(+) ions on a rotatable and heatable stage. Irradiation at elevated temperatures above 300 °C retains the geometry of the nanostructure and sputtering can be gauged accurately. The diameter dependence of the sputtering shows a maximum if the ion range matches the nanowire diameter, which is in good agreement with Monte Carlo simulations based on binary collisions. Nanowires irradiated at room temperature, however, amorphize and deform plastically. So far, plastic deformation has not been observed in bulk silicon at such low ion energies. The magnitude and direction of the deformation is independent of the ion-beam direction and cannot be explained with mass-transport in a binary collision cascade but only by collective movement of atoms in the collision cascade with the given boundary conditions of a high surface to volume ratio.

Thalidomide as palliative treatment in patients with advanced secondary glioblastoma.

BACKGROUND: For its numerous abilities including sedation, we have been using thalidomide (TH) as the 'last therapeutic option' in patients with advanced gliomas. We noticed that a small subgroup, i.e. patients with secondary glioblastoma (GBM, whose GBM has evolved over several months or years from a less malignant glioma), survived for prolonged periods. Therefore, we retrospectively evaluated the outcomes of patients with secondary GBM treated with TH at our centre. PATIENTS AND METHODS: Starting in the year 2000, we have studied 23 patients (13 females, 10 males, with a median age of 31.5 years) with secondary GBM who have received palliative treatment with TH 100 mg at bedtime. All patients had previously undergone radiotherapy and received at least 1 and up to 5 regimens of chemotherapy. RESULTS: The median duration of TH administration was 4.0 months (range 0.8-32). The median duration of overall survival after the start of TH therapy was 18.3 months (range 0.8-57). Eleven patients with secondary GBM survived longer than 1 year. Symptomatic improvement was most prominent in the restoration of a normal sleep pattern. CONCLUSION: The palliative effects of TH, especially the normalization of a sleep pattern, were highly valued by patients and families. The prolongation of survival of patients with secondary GBM has not been reported previously.

Magnetic polarons and large negative magnetoresistance in GaAs nanowires implanted with Mn ions.

We report on low-temperature magnetotransport and SQUID measurements on heavily doped Mn-implanted GaAs nanowires. SQUID data recorded at low magnetic fields exhibit clear signs of the onset of a spin-glass phase with a transition temperature of about 16 K. Magnetotransport experiments reveal a corresponding peak in resistance at 16 K and a large negative magnetoresistance, reaching 40% at 1.6 K and 8 T. The negative magnetoresistance decreases at elevated temperatures and vanishes at about 100 K. We interpret our transport data in terms of spin-dependent hopping in a complex magnetic nanowire landscape of magnetic polarons, separated by intermediate regions of Mn impurity spins, forming a paramagnetic/spin-glass phase.

Factors associated with the Single Leg Squat test in female soccer players: a cross-sectional study.

BACKGROUND: The Single Leg Squat (SLS) test is widely used in the clinical setting to examine and evaluate rehabilitation goals. It is simple to perform and is proposed to have biomechanical and neuromuscular similarities to athletic movements. The aim of the present study was to investigate whether demographics, previous injuries, and biomechanical and psychosocial factors are associated with the outcome of the SLS, assessed as a total score for all segments and as a separate knee segment in elite and sub-elite female soccer players. METHODS: We conducted a cross-sectional study involving 254 female soccer players (22 yrs; SD ± 4, height 1.69 m; SD ± 0.1, weight 64 kg; SD ± 6) from divisions 1-3 of the Swedish Soccer League. During the preseason, we assessed the participants using the SLS and tested their hip strength and ankle mobility. Demographics, previous injury, sleep quality, fear of movement, anxiety, and perceived stress were assessed with questionnaires. Logistic regression models were built to analyse the association between the outcome of the SLS and the independent variables for the dominant and non-dominant leg. RESULTS: Significantly more participants failed the SLS on the dominant leg compared with the non-dominant leg (p < 0.001). The outcome of the SLS associated with various biopsychosocial factors depending on if the dominant or non-dominant leg was tested. The total score associated with hip strength for the dominant (OR 0.99, 95% CI 0.98-0.99, p = 0.04) and the non-dominant leg (OR 0.99, 95% CI 0.97-0.99, p = 0.03). The knee segment associated with division level for the dominant (div 2; OR 2.34, 95% CI 1.01-5.12, p = 0.033. div 3; OR 3.07, 95% CI 1.61-5.85, p = 0.001) and non-dominant leg (div 2; OR 3.30, 95% CI 1.33-8.00, p = 0.01. div 3; OR 3.05, 95% CI 1.44-6.43, p = 0.003). CONCLUSIONS: This study identified that leg dominance, division level, hip strength, and psychosocial factors were associated with the outcome of the SLS when assessed as a total score and as a separate knee segment. This indicates that clinicians need to understand that movement control is associated with factors from several domains. Whether these factors and, the results of the SLS are related to injury need to be studied prospectively. TRIAL REGISTRATION: Clinical Trials Gov, date of registration 2022-03-01. CLINICAL TRIALS IDENTIFIER: NCT05289284A.

Bone mineral properties and 3D orientation of human lamellar bone around cement lines and the Haversian system.

Bone is a complex, biological tissue made up primarily of collagen fibrils and biomineral nanoparticles. The importance of hierarchical organization in bone was realized early on, but the actual interplay between structural features and the properties on the nanostructural and crystallographic level is still a matter of intense discussion. Bone is the only mineralized tissue that can be remodeled and, at the start of the formation of new bone during this process, a structure called a cement line is formed on which regular bone grows. Here, the orientational relationship of nanostructural and crystallographic constituents as well as the structural properties of both nanostructural and crystallographic constituents around cement lines and the Haversian system in human lamellar bone are investigated. A combination of small- and wide-angle X-ray scattering tensor tomography is employed together with diffraction tomography and synchrotron computed tomography to generate a multi-modal image of the sample. This work shows that the mineral properties vary as a function of the distance to the Haversian canal and, importantly, shows that the cement line has differing mineral properties from the surrounding lamellar bone, in particular with respect to crystallite size and degree of orientation. Cement lines make up a significant portion of the bone matrix despite their small size, hence the reported findings on an altered mineral structure, together with the spatial modulation around the Haversian canal, have implications for the formation and mechanics of bone.

Bone mineral properties and 3D orientation of human lamellar bone around cement lines and the Haversian system. Corrigendum.

The article by Grünewald et al. [IUCrJ (2023). 10, 189-198] is corrected.