Investigating bone resorption in Atlantic herring fish intermuscular bones with solid-state NMR.

Bones are connective tissues mainly made of collagen proteins with calcium phosphate deposits. They undergo constant remodeling, including destroying existing bones tissues (known as bone resorption) and rebuilding new ones. Bone remodeling has been well-described in mammals, but it is not the case in fish. Here, we focused on the mobile phase of the bone vascular system by carefully preserving moisture in adult Atlantic herring intermuscular bones. We detected pore water with high ionic strength and soluble degraded peptides whose 1H-transverse relaxation times, T2s, exceed 15 milliseconds. With favorable T2s, we incorporated a solution state spinlock scheme into the INEPT techniques to unequivocally demonstrate collagen degradation. In addition, we detected a substantial amount of inorganic phosphate in solution with 31P-NMR in the considerable background of solid hydroxyapatite calcium phosphate by saturation recovery experiment. It is consistent with the idea that bone resorption degrades bone collagen and releases calcium ions and phosphate ions in the pore water with increased ionic strength. Our report is the first to probe the resorption process in the heterogenous bone microstructure with a rigorous characterization of 1H and 13C relaxation behavior and direct assignments. In addition, we contribute to the fish bones literature by investigating fish bone remodeling using NMR for the first time.

Knee Pain from Osteoarthritis: Pathogenesis, Risk Factors, and Recent Evidence on Physical Therapy Interventions.

For patients presenting knee pain coming from osteoarthritis (OA), non-pharmacological conservative treatments (e.g., physical therapy interventions) are among the first methods in orthopedics and rehabilitation to prevent OA progression and avoid knee surgery. However, the best strategy for each patient is difficult to establish, because knee OA's exact causes of progression are not entirely understood. This narrative review presents (i) the most recent update on the pathogenesis of knee OA with the risk factors for developing OA and (ii) the most recent evidence for reducing knee pain with physical therapy intervention such as Diathermy, Exercise therapy, Ultrasounds, Knee Brace, and Electrical stimulation. In addition, we calculated the relative risk reduction in pain perception for each intervention. Our results show that only Brace interventions always reached the minimum for clinical efficiency, making the intervention significant and valuable for the patients regarding their Quality of Life. In addition, more than half of the Exercise and Diathermy interventions reached the minimum for clinical efficiency regarding pain level. This literature review helps clinicians to make evidence-based decisions for reducing knee pain and treating people living with knee OA to prevent knee replacement.

Theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization.

Bone is a hard-soft biomaterial built through a self-assembly process under genetic regulatory network (GRN) monitoring. This paper aims to capture the behavior of the bone GRN part that controls mineralization by using a mathematical model. Here, we provide an advanced review of empirical evidence about interactions between gene coding (i) transcription factors and (ii) bone proteins. These interactions are modeled with nonlinear differential equations using Michaelis-Menten and Hill functions. Compared to empirical evidence - coming from osteoblasts culture -, the two best systems (among 126=2,985,984 possibilities) use factors of inhibition from the start of the activation of each gene. It reveals negative indirect interactions coming from either negative feedback loops or the recently depicted micro-RNAs. The difference between the two systems also lies in the BSP equation and two ways for activating and reducing its production. Thus, it highlights the critical role of BSP in the bone GRN that acts on bone mineralization. Our study provides the first theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization with this work.

Systematic Review Shows Tele-Rehabilitation Might Achieve Comparable Results to Office-Based Rehabilitation for Decreasing Pain in Patients with Knee Osteoarthritis.

Background and Objectives This systematic review aims to evaluate the efficacy of Tele-Rehabilitation for decreasing pain in patients with knee osteoarthritis (OA). Materials and Methods: Following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), three electronic databases (CINAHL, PubMed, PEDro), along with the addition of grey literature, were used to collect information. Randomized control trials (RCTs) comparing tele-rehabilitation (TR) to office-based-rehabilitation (OB) were critically appraised using the 2005 University of Oxford Standard. A total of 139 articles (PubMed = 132, CINAHL = 5, PEDro = 0, grey literature = 2) were acquired. Results: After the screening, three RCTs were included in our review. Their results show no statistically significant differences between TR and OB intervention. Furthermore, their results showed an overall reduction in pain in both groups from the baseline to the end of the study. However, each intervention's clinical efficiency was dependent on the exercise protocol itself and not on the method of delivery. There is a potential ceiling effect to the amount of therapy a patient can receive in which additional therapy would no longer lead to improved recovery. Conclusions: Our review suggests evidence that TR's efficacy is similar to that of OB for improvement of WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score parameters in patients suffering from knee OA.

Long-Chain Fatty Acids in Bones and Their Link to Submicroscopic Vascularization Network: NMR Assignment and Relaxation Studies under Magic Angle Spinning Conditions in Intramuscular Bones of Atlantic Herring Fish.

The long-lasting proton signals in bones are identified as long-chain fatty acids, including saturated, mono-, and di-unsaturated fatty acids, with direct nuclear magnetic resonance evidence. We used intramuscular bones from Atlantic Herring fish to avoid interference from lipid-rich marrows. The key is to recognize that these signals are from mobile phase materials and study them with J-coupled correlation spectroscopies under magic angle spinning conditions. We kept extensive 1H-spin-echo records that allowed us to examine the effect of magic angle spinning on the transverse relaxation time of water and lipids over time. While it is impossible to distinguish based on chemical shifts, the relaxation data suggest that the signals are more consistent with the interpretation of phospholipid membranes than triglycerides in lipid droplets. In particular, the simultaneous T2 changes in water and lipids suggest that the centrifugal impact of magic angle spinning alters the lipid's structure in very tight spaces. Additional evidence of phospholipid membranes came from the choline-γ resonance at 3.2 ppm in fresh samples, which disappears with magic angle spinning. Thus, the fatty acid signals are at least partially from membrane bilayer structures, and we propose that they are linked to the submicroscopic vascularization channels similar to the dense canaliculi network in mammalian bones. Our detection of phospholipids from bones depended critically on two factors: (1) the elimination of the overwhelming triglyceride signals from marrows and (2) the preservation of water that biomembranes require. The relaxation data reveal aspects of lipid fluidity that have not been elucidated by previous order parameter studies on model membranes. Relaxation times have long been considered difficult to interpret. A robust and renewed understanding may be beneficial.

Systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.

BACKGROUND: A recent trend in the field of primary knee osteoarthritis suggests that elastic tape (e.g., K-tape) relieves pressure on the joint by increasing tension on fascia. Elastic tape (ET) is expected to decrease pain and help patients to recover faster. OBJECTIVE: This systematic review aims to analyze the efficacy of this method on pain in patients with knee osteoarthritis by using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. DATA SOURCES: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for reporting systematic reviews of qualitative and quantitative evidence, we used 3 electronic databases, PubMed, Cochrane, and EBSCO, and grey literature was included. STUDY ELIGIBILITY CRITERIA: Articles were screened for duplicates, screened for inclusion and exclusion criteria, and critically appraised. PARTICIPANTS AND INTERVENTION: People older than 45 years old with primary osteoarthritis (OA) and application of ET. STUDY APPRAISAL AND SYNTHESIS METHODS: 2005 Oxford standard. RESULTS: Amongst all the papers found, 6 Randomized Control Trials (RCT) for a total of 392 participants met the criteria and were included in our review. Three papers out of the 6 RCT had low risks of bias. When the ET was compared to sham taping, the results show no to moderate decreases of WOMAC scores in patients with primary knee osteoarthritis. LIMITATIONS: We focused on a single index test (WOMAC) and could not perform meta-analyses. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Although ET does not provide strong adverse outcomes, our data do not support the use of ET as a treatment alone because of too slight reductions of the WOMAC score for reaching clinical efficiency. Thus, our systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.

New Guidelines for Electrical Stimulation Parameters in Adult Patients With Knee Osteoarthritis Based on a Systematic Review of the Current Literature.

OBJECTIVE: The goal of this systematic review was to provide guidelines for treatment parameters regarding electrical stimulation by investigating its efficacy in improving muscle strength and decreasing pain in patients with knee osteoarthritis. DESIGN: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard, three electronic databases (CINAHL, PubMed, and PEDro) and gray literature were used. Randomized control trials comparing electrical stimulation and conservative physical therapy were critically appraised using the 2005 University of Oxford standard. RESULTS: Nine randomized control trials were included in our review. First, our review confirmed that neuromuscular electrical stimulation is the most effective electrical stimulation treatment in the management of knee OA, and its efficiency is higher when combined with a strengthening program. Second, frequency of at least 50 Hz and no more than 75 Hz with a pulse duration between 200 and 400 µs and a treatment duration of 20 mins is necessary for successful treatment. CONCLUSIONS: For the first time, our review provides standardized clinical treatment parameters for neuromuscular electrical stimulation to be included in a strengthening program for the adult patient with knee OA. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Recall the impact of quadriceps femoris weakness on joint stability; (2) Summarize the mechanism of action of neuromuscular electrical stimulation (NMES) on reducing pain and increasing muscle strength; and (3) Plan the clinical treatment parameters of NMES to be included in a strengthening program for an adult patient with knee osteoarthritis. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Raman spectroscopy investigation shows that mineral maturity is greater in CD-1 than in C57BL/6 mice distal femurs after sexual maturity.

Purpose/Aim of the study mice are the most often used pre-clinical lab models for studying the pathologies of bone mineralization. However, recent evidence suggests that two of the most often used mice strains (C57BL/6J and CD-1) might show differences in the bone mineralization process. This study sought to investigate the main compositional properties of bone tissue between nonpathological C57BL/6J and CD-1 murine knee joints. Materials and Methods : to this end, medial and lateral condylar subchondral bones and the adjacent diaphyseal cortical bone of 13 murine femurs (n = 7 C57BL/6J and n = 6 CD-1 at eight weeks old, just after sexual maturation) were analyzed with ex vivo Raman spectroscopy. Results : regardless of the bone tissue analyzed, our results showed that CD-1 laboratory mice present a more mature mineral phase than C57BL/6J laboratory mice, but present no difference in maturity of the collagen phase. For both strains, the subchondral bone of the medial condylar and cortical bone from the diaphysis have similar compositional properties, and CD-1 presents less variation than C57BL/6J. Furthermore, we depict a novel parametric relationship between the crystallinity and carbonate-to-amide-I ratio that might help in deciphering the mineral maturation process that occurs during bone's mineralization. Conclusions : Our results suggest that the timing of bone maturation might be different between non-pathological C57BL/6J and CD-1 murine knee femurs.

A novel approach for computing 3D mice distal femur properties using high-resolution micro-computed tomography scanning.

One of the most-scanned joints in preclinical animal models dealing with musculoskeletal pathologies is the mouse knee. While three-dimensional (3D) characterization of bone tissue porosity have previously been performed on cortical bone, it has not yet been comprehensively performed for the subchondral bone (SB) and the calcified cartilage (CC), which compose the subchondral mineralized zone (SMZ). Thus, it remains challenging to assess changes that occur in the SMZ of the mouse knee during pathologies such as osteoarthritis. One of the keys to addressing this challenge is to segment each layer to measure their morphologies, material properties, and porosity. Our study presents a novel approach for computing Tissue Mineral Density, 3D porosity, and the thickness of SB and CC in a mouse distal femur using High-Resolution Micro-Computed Tomography (HR-µCT). We have segmented the Vascular Porosity network, the osteocytes' lacunae of the SB, and the chondrocytes of the CC by using multi-thresholding and the percentage of chondrocytes porosity. Our results show a low intra- and inter-observer coefficient of variability. Regarding porosity and geometrical properties of both CC and SB, our results are within the range of the literature. Our approach opens new avenues for assessing porosity and vascular changes in the distal femur of preclinical animal models dealing with musculoskeletal pathologies such as osteoarthritis.

A Novel Multiscale Mathematical Model for Building Bone Substitute Materials for Children.

Bone is an engineering marvel that achieves a unique combination of stiffness and toughness exceeding that of synthesized materials. In orthopedics, we are currently challenged for the child population that needs a less stiff but a tougher bone substitute than adults. Recent evidence suggests that the relationship between inter-molecular connections that involve the two main bone building blocks, TropoCollagen molecules (TC) and carbonated Hydroxyapatite (cAp), and bone macroscopic mechanical properties, stiffness and toughness, are key to building bone substitute materials for children. The goal of our study is to establish how inter-molecular connections that occur during bone mineralization are related to macroscopic mechanical properties in child bones. Our aim is to link the biological alterations of the TC-cAp self assembly process happening during bone mineralization to the bone macroscopic mechanical properties' alterations during aging. To do so, we have developed a multiscale mathematical model that includes collagen cross links (TC⁻TC interface) from experimental studies of bone samples to forecast bone macroscopic mechanical properties. Our results support that the Young's modulus cannot be a linear parameter if we want to solve our system. In relation to bone substitute material with innovative properties for children, our results propose values of several biological parameters, such as the number of crystals and their size, and collagen crosslink maturity for the desired bone mechanical competence. Our novel mathematical model combines mineralization and macroscopic mechanical behavior of bone and is a step forward in building mechanically customized biomimetic bone grafts that would fit children's orthopedic needs.

The different distribution of enzymatic collagen cross-links found in adult and children bone result in different mechanical behavior of collagen.

Enzymatic collagen cross-linking has been shown to play an important role in the macroscopic elastic and plastic deformation of bone across ages. However, its direct contribution to collagen fibril deformation is unknown. The aim of this study is to determine how covalent intermolecular connections from enzymatic collagen cross-links contribute to collagen fibril elastic and plastic deformation of adults and children's bone matrix. We used ex vivo data previously obtained from biochemical analysis of children and adults bone samples (n = 14; n = 8, respectively) to create 22 sample-specific computational models of cross-linked collagen fibrils. By simulating a tensile test for each fibril, we computed the modulus of elasticity (E), ultimate tensile and yield stress (σu and σy), and elastic, plastic and total work (We, Wp and Wtot) for each collagen fibril. We present a novel difference between children and adult bone in the deformation of the collagen phase and suggest a link between collagen fibril scale and macroscale for elastic behavior in children bone under the influence of immature enzymatic cross-links. We show a parametric linear correlation between We and immature enzymatic collagen cross-links at the collagen fibril scale in the children population that is similar to the one we found at the macroscale in our previous study. Finally, we suggest the key role of covalent intermolecular connections to stiffness parameters (e.g. elastic modulus and We) in children's collagen fibril and to toughness parameters in adult's collagen fibril, respectively.

Ratio between mature and immature enzymatic cross-links correlates with post-yield cortical bone behavior: An insight into greenstick fractures of the child fibula.

As a determinant of skeletal fragility, the organic matrix is responsible for the post-yield and creep behavior of bone and for its toughness, while the mineral apatite acts on stiffness. Specific to the fibula and ulna in children, greenstick fractures show a plastic in vivo mechanical behavior before bone fracture. During growth, the immature form of collagen enzymatic cross-links gradually decreases, to be replaced by the mature form until adolescence, subsequently remaining constant throughout adult life. However, the link between the cortical bone organic matrix and greenstick fractures in children remains to be explored. Here, we sought to determine: 1) whether plastic bending fractures can occur in vitro, by testing cortical bone samples from children's fibula and 2) whether the post-yield behavior (ωp plastic energy) of cortical bone before fracture is related to total quantity of the collagen matrix, or to the quantity of mature and immature enzymatic cross-links and the quantity of non-enzymatic cross-links. We used a two-step approach; first, a 3-point microbending device tested 22 fibula machined bone samples from 7 children and 3 elderly adults until fracture. Second, biochemical analysis by HPLC was performed on the sample fragments. When pooling two groups of donors, children and elderly adults, results show a rank correlation between total energy dissipated before fracture and age and a linear correlation between plastic energy dissipated before fracture and ratio of immature/mature cross-links. A collagen matrix with more immature cross-links (i.e. a higher immature/mature cross-link ratio) is more likely to plastically deform before fracture. We conclude that this ratio in the sub-nanostructure of the organic matrix in cortical bone from the fibula may go some way towards explaining the variance in post-yield behavior. From a clinical point of view, therefore, our results provide a potential explanation of the presence of greenstick fractures in children.

Morphological and biomechanical analyses of the subchondral mineralized zone in human sacral facet joints: Application to improved diagnosis of osteoarthritis.

The anatomy of the facet joint subchondral mineralized zone (SMZ) is the main parameter used in diagnosing osteoarthritis. Usually, a single CT scan slice is used to measure the thickness, but the measurement is highly location-dependent. Bone mineral density (BMD) and porosity could be more reliable than thickness for detecting SMZ sclerosis, and linking them to stiffness can provide insights into the mechanism of osteoarthritis progression. The goal of this study was two-fold: (1) to assess spatial heterogeneity in thickness, BMD, and porosity within the non-pathological human facet joint SMZ; (2) to correlate these measurements with the static modulus of elasticity (MOEsta ). Four non-pathological facet joints were excised and imaged using micro-computed tomography (µCT) to measure SMZ thickness, BMD, and porosity. A total of eight parallelepiped SMZ samples were similarly analyzed and then mechanically tested. The mean SMZ BMD, porosity, and thickness (± Standard Deviation) of the whole facet joints were 611 ± 35 mgHA/cc, 9.8 ± 1.3%, and 1.39 ± 0.41 mm, respectively. The mean BMD, porosity, and MOEsta of the eight SMZ samples were 479 ± 23 mgHA/cc, 12 ± 0.01%, and 387 ± 138 MPa, respectively, with a positive rank correlation between BMD and porosity. BMD and porosity were more homogeneous within the facet joint than thickness and they could be more reliable parameters than thickness for detecting SMZ sclerosis. The values for the physiological SMZ and MOEsta of human facets joints obtained here were independent of BMD. SMZ BMD and porosity were related to each other.

In vitro ultrasonic and mechanic characterization of the modulus of elasticity of children cortical bone.

The assessment of elastic properties in children's cortical bone is a major challenge for biomechanical engineering community, more widely for health care professionals. Even with classical clinical modalities such as X-ray tomography, MRI, and/or echography, inappropriate diagnosis can result from the lack of reference values for children bone. This study provides values for elastic properties of cortical bone in children using ultrasonic and mechanical measurements, and compares them with adult values. 18 fibula samples from 8 children (5-16 years old, mean age 10.6 years old ±4.4) were compared to 16 fibula samples from 3 elderly adults (more than 65 years old). First, the dynamic modulus of elasticity (Edyn) and Poisson's ratio (ν) are evaluated via an ultrasonic method. Second, the static modulus of elasticity (Esta) is estimated from a 3-point microbending test. The mean values of longitudinal and transverse wave velocities measured at 10 MHz for the children's samples are respectively 3.2mm/µs (±0.5) and 1.8mm/µs (±0.1); for the elderly adults' samples, velocities are respectively 3.5mm/µs (±0.2) and 1.9 mm/µs (±0.09). The mean Edyn and the mean Esta for the children's samples are respectively 15.5 GPa (±3.4) and 9.1 GPa (±3.5); for the elderly adults' samples, they are respectively 16.7 GPa (±1.9) and 5.8 GPa (±2.1). Edyn, ν and Esta are in the same range for children's and elderly adults' bone without any parametric statistical difference; a ranking correlation between Edyn and Esta is shown for the first time.

The effect of nucleotomy on facet joint loading - a porcine in vitro study.

BACKGROUND: Lumbar facet joints have been cited as a possible origin of low-back pain. A relationship between disc height decrease and facet joint degeneration has been reported. Facet joint degeneration may also be triggered by nucleotomy, performed on prolapsed discs, which might change the natural load sharing between the anterior and posterior structures of the spine. In this study load bearing of the facet joints was compared between natural and nucleotomised spinal segments. METHODS: Nine porcine lumbar motion segments were tested quasi-statically in ±1.5° extension-flexion under 700 N constant compression loading. The kinematics of the spinal segments were recorded as a response to the applied load. These kinematics were subsequently applied to the segments with the ligaments and disc sequentially removed and the reaction forces measured. This was performed in samples with and without nucleotomy. Comparison of the reaction forces allowed a direct comparison between healthy and pathological force transmission over the facet joints. Load sharing was related to the proportion of removed nucleus. FINDINGS: The proportion of applied compression force supported by the facets increased from a mean of 40.7% (standard deviation, SD 10.0%) to 82.0% (SD 7.2%) after nucleotomy averaged over the entire extension-flexion regime. No correlation was observed between facet loading and the proportion of the nucleus removed. INTERPRETATION: Increased facet loading after nucleotomy might cause greater cartilage wear, which may be related to facet joint degeneration. The independence of facet loading on the proportion of nucleus removed might be due to a complete pressure loss once the annulus is incised.

Beyond the classic correction system: a numerical nonrigid approach to the scoliosis brace.

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) causes a spine and rib cage three-dimensional (3D) deformity previously treated by bracing. Whatever the manufacturing process, this rigid system acts biomechanically on the patient through the "three-point bending" mechanical principle. It applies corrective forces to a limited area and acts especially in the frontal plane. It seemed to us that a nonrigid system, called "Cbrace," with 3D action allowing distribution of forces could increase compliance and provide better long-term correction prospects. PURPOSE: The aim of this study was to design a nonrigid brace by numerically testing in a finite-element model developed here. STUDY DESIGN: A finite-element model has been developed to simulate brace effect on AIS right thoracic deformation of a 10-year-old patient. METHODS: A two-step method was needed; first, the reliability of our model is evaluated, and then, the ability to use distributed forces to correct scoliosis deformation is tested. To obtain a 3D correction, several treatments are experimented, leading to a comparison test between the best combination to the "three-point bending" principle. RESULTS: The numerical model developed here shows good qualitative answers for the treatment of brace forces. The first results demonstrate numerically that distributed forces may be of interest in brace treatment design. Overall force of 40 N above cartilage of the last nonfloating ribs associated to two posterior asymmetrical areas appears to be the best way to correct scoliosis deformation with nonrigid action. CONCLUSION: The results show numerical efficacy of distributed forces to correct spinal deformities and raises the prospect that a new numerical brace, called "Cbrace," could be a starting point in the search for a nonrigid system.