scholarly journals Study TPX-100-5: Intra-Articular TPX-100 Significantly Delays Pathological Bone Shape Change and Stabilizes Cartilage in Moderate to Severe Bilateral Knee OA

2021 ◽  
Author(s):  
Dawn McGuire ◽  
Michael Bowes ◽  
Alan Brett ◽  
Neil Segal ◽  
Meghan Miller ◽  
...  
Keyword(s):  
Internal Control ◽  
Function Versus ◽  
Shape Change ◽  
Cartilage Thickness ◽  
Cartilage Defects ◽  
Knee Cartilage ◽  
Knee Oa ◽  
Bilateral Knee ◽  
The Relationship ◽  
Shape Changes

Abstract Background: TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months.Methods: 104 participants with bilateral knee moderate to severe (ICRS 2-4) knee cartilage defects were randomized for evaluation of efficacy and safety of 200mg of TPX-100. Each subject’s contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were centrally performed, blind to treatment assignment and clinical data.Results: TPX-100-treated knees (n=78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. -0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P=0.02); and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P<0.01). Conclusions: This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC function versus placebo, support TPX-100 as a candidate for disease modification in knee OA.Trial Registration: NIH clinicaltrials.gov, NCT01925261. Registered 15 August 2013, https://clinicaltrials.gov/ct2/show/NCT01925261?term=NCT01925261

scholarly journals Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Dawn McGuire ◽  
Michael Bowes ◽  
Alan Brett ◽  
Neil A. Segal ◽  
Meghan Miller ◽  
...  
Keyword(s):  
Internal Control ◽  
Function Versus ◽  
Shape Change ◽  
Cartilage Thickness ◽  
Cartilage Defects ◽  
Knee Cartilage ◽  
Knee Oa ◽  
To Receive ◽  
The Relationship ◽  
Shape Changes

Abstract Background TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months. Methods One hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject’s contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data. Results TPX-100-treated knees (n = 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. − 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P = 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P < 0.01). Conclusions This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA. Trial registration NIH ClinicalTrials.gov, NCT01925261. Registered 15 August 2013

Hand Joint Space Narrowing and Osteophytes Are Associated with Magnetic Resonance Imaging-defined Knee Cartilage Thickness and Radiographic Knee Osteoarthritis: Data from the Osteoarthritis Initiative

2011 ◽  
Vol 39 (1) ◽  
pp. 161-166 ◽  
Author(s):  
IDA K. HAUGEN ◽  
SEBASTIAN COTOFANA ◽  
MARTIN ENGLUND ◽  
TORE K. KVIEN ◽  
DONATUS DREHER ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Joint Space Narrowing ◽  
Joint Space ◽  
Cartilage Thickness ◽  
Resonance Imaging ◽  
Knee Cartilage ◽  
Knee Oa ◽  
Osteoarthritis Initiative ◽  
Hand Radiographs

Objective.To evaluate whether features of radiographic hand osteoarthritis (OA) are associated with quantitative magnetic resonance imaging (MRI)-defined knee cartilage thickness, radiographic knee OA, and 1-year structural progression.Methods.A total of 765 participants in Osteoarthritis Initiative (OAI; 455 women, mean age 62.5 yrs, SD 9.4) obtained hand radiographs (at baseline), knee radiographs (baseline and Year 1), and knee MRI (baseline and Year 1). Hand radiographs were scored for presence of osteophytes and joint space narrowing (JSN). Knee radiographs were scored according to the Kellgren-Lawrence (KL) scale. Cartilage thickness in the medial and lateral femorotibial compartments was measured quantitatively from coronal FLASHwe images. We examined the cross-sectional and longitudinal associations between features of hand OA (total osteophyte and JSN scores) and knee cartilage thickness, 1-year knee cartilage thinning (above smallest detectable change), presence of knee OA (KL grade ≥ 3), and progression of knee OA (KL change ≥ 1) by linear and logistic regression. Both hand OA features were included in a multivariate model (if p ≤ 0.25) adjusted for age, sex, and body mass index (BMI).Results.Hand JSN was associated with reduced knee cartilage thickness (ß = −0.02, 95% CI −0.03, −0.01) in the medial femorotibial compartment, while hand osteophytes were associated with the presence of radiographic knee OA (OR 1.10, 95% CI 1.03–1.18; multivariate models) with both hand OA features as independent variables adjusted for age, sex, and BMI). Radiographic features of hand OA were not associated with 1-year cartilage thinning or radiographic knee OA progression.Conclusion.Our results support a systemic OA susceptibility and possibly different mechanisms for osteophyte formation and cartilage thinning.

Platelet Shape Change Evoked by Selective Activation of P2X1 Purinoceptors with α,β-Methylene ATP

2001 ◽  
Vol 85 (02) ◽  
pp. 303-308 ◽  
Author(s):  
Michael Rolf ◽  
Charles Brearley ◽  
Martyn Mahaut-Smith
Keyword(s):  
Inhibitory Action ◽  
Light Transmission ◽  
Shape Change ◽  
Second Messengers ◽  
Receptor Activation ◽  
Selective Activation ◽  
The Relationship ◽  
Shape Changes ◽  
Platelet Shape

SummarySimultaneous measurements of [Ca2+]i and light transmission were used to examine the relationship between P2X1 receptor activation and functional platelet responses. The P2X1 agonist α,β-MeATP evoked a transient [Ca2+]i increase and a reversible decrease in light transmission; both responses required external Ca2+ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. α,β-MeATP stimulated smaller shape changes than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for α,β-MeATP-evoked [Ca2+]i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X1 agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.

scholarly journals Knee Cartilage Thickness Differs Alongside Ages: A 3-T Magnetic Resonance Research Upon 2,481 Subjects via Deep Learning

2021 ◽  
Vol 7 ◽  
Author(s):  
Liping Si ◽  
Kai Xuan ◽  
Jingyu Zhong ◽  
Jiayu Huo ◽  
Yue Xing ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Deep Learning ◽  
Magnetic Resonance ◽  
Knee Joint ◽  
Magnetic Resonance Images ◽  
Cartilage Thickness ◽  
Imaging Data ◽  
Knee Cartilage ◽  
Large Collection ◽  
The Relationship

Background: It was difficult to distinguish the cartilage thinning of an entire knee joint and to track the evolution of cartilage morphology alongside ages in the general population, which was of great significance for studying osteoarthritis until big imaging data and artificial intelligence are fused. The purposes of our study are (1) to explore the cartilage thickness in anatomical regions of the knee joint among a large collection of healthy knees, and (2) to investigate the relationship between the thinning pattern of the cartilages and the increasing ages.Methods: In this retrospective study, 2,481 healthy knees (subjects ranging from 15 to 64 years old, mean age: 35 ± 10 years) were recruited. With magnetic resonance images of knees acquired on a 3-T superconducting scanner, we automatically and precisely segmented the cartilage via deep learning and calculated the cartilage thickness in 14 anatomical regions. The thickness readings were compared using ANOVA by considering the factors of age, sex, and side. We further tracked the relationship between the thinning pattern of the cartilage thickness and the increasing ages by regression analysis.Results: The cartilage thickness was always thicker in the femur than corresponding regions in the tibia (p &lt; 0.05). Regression analysis suggested cartilage thinning alongside ages in all regions (p &lt; 0.05) except for medial and lateral anterior tibia in both females and males (p &gt; 0.05). The thinning speed of men was faster than women in medial anterior and lateral anterior femur, yet slower in the medial patella (p &lt; 0.05).Conclusion: We established the calculation method of cartilage thickness using big data and deep learning. We demonstrated that cartilage thickness differed across individual regions in the knee joint. Cartilage thinning alongside ages was identified, and the thinning pattern was consistent in the tibia while inconsistent in patellar and femoral between sexes. These findings provide a potential reference to detect cartilage anomaly.

scholarly journals Geometric morphometric analysis of cyclical body shape changes in color pattern variants of Cichla temensis Humboldt, 1821 (Perciformes: Cichlidae) demonstrates reproductive energy allocation

2015 ◽  
Vol 13 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Paul Reiss ◽  
Thomas M. Grothues
Keyword(s):  
Sexual Maturity ◽  
Shape Change ◽  
Flood Pulse ◽  
Color Pattern ◽  
Geometric Morphometric ◽  
Geometric Morphometric Analysis ◽  
Local Water ◽  
Relationship Of ◽  
The Relationship ◽  
Shape Changes

Previously recognized color and pattern variants of adult Cichla temensis in Amazon flood pulse river environments reflect the cycling of individuals through seasonal sexual maturity and spawning. Individuals also vary in shape from blocky to fusiform. To determine if shape differences are related to patterns of fat reserve deposition and utilization, and to quantify the relationship of shape with color and pattern variation and life history status, specimens in each of four previously defined grades of color and pattern variation were compared using geometric morphometric techniques. Progressive shape changes occurred between grades independent of sex and correlated to gonosomatic index (GSI). Thin plate spline deformation visualizations indicate that the observed shape differences are related to fat deposition patterns. The seasonal timing of shape change and its link to color pattern variation, sexual maturity and local water level conditions suggests a relationship between the physiological and behavioral characteristics of C. temensis and the cyclical flood pulse pattern of its habitat.

scholarly journals Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage

2011 ◽  
Vol 71 (1) ◽  
pp. 26-32 ◽  
Author(s):  
A Anandacoomarasamy ◽  
S Leibman ◽  
G Smith ◽  
I Caterson ◽  
B Giuffre ◽  
...  
Keyword(s):  
Weight Loss ◽  
Lateral Compartment ◽  
Cartilage Thickness ◽  
Knee Cartilage ◽  
Percentage Weight Loss ◽  
Knee Oa ◽  
Percentage Weight ◽  
Proteoglycan Content ◽  
Dgemric Index ◽  
The Impact

BackgroundObesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed.ObjectivesTo assess the impact of weight loss on knee cartilage thickness and composition.Methods111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA.ResultsMean age was 51.7±11.8 years and mean BMI was 36.6±5.8 kg/m2; 32% had clinical knee OA. Mean weight loss was 9.3±11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (β=0.006, r2=0.19, p=0.029). This association was not detected in the lateral compartment (r2=0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (β=3.9, r2=0.26; p=0.008) but not the lateral compartment (r2=0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r2=0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%.ConclusionsWeight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications.

scholarly journals Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Raphaël Etournay ◽  
Marko Popović ◽  
Matthias Merkel ◽  
Amitabha Nandi ◽  
Corinna Blasse ◽  
...  
Keyword(s):  
Mechanical Model ◽  
Cell Shape ◽  
Shape Change ◽  
Cell Dynamics ◽  
Blade Shape ◽  
Pupal Wing ◽  
The Right ◽  
And Behavior ◽  
The Relationship ◽  
Shape Changes

How tissue shape emerges from the collective mechanical properties and behavior of individual cells is not understood. We combine experiment and theory to study this problem in the developing wing epithelium of Drosophila. At pupal stages, the wing-hinge contraction contributes to anisotropic tissue flows that reshape the wing blade. Here, we quantitatively account for this wing-blade shape change on the basis of cell divisions, cell rearrangements and cell shape changes. We show that cells both generate and respond to epithelial stresses during this process, and that the nature of this interplay specifies the pattern of junctional network remodeling that changes wing shape. We show that patterned constraints exerted on the tissue by the extracellular matrix are key to force the tissue into the right shape. We present a continuum mechanical model that quantitatively describes the relationship between epithelial stresses and cell dynamics, and how their interplay reshapes the wing.

scholarly journals Correlation Between Weight Bearing Asymmetry and Bone Mineral Density in Patients With Bilateral Knee Osteoarthritis

2021 ◽  
Author(s):  
Kohei Nishizawa ◽  
Kengo Harato ◽  
Yutaro Morishige ◽  
Shu Kobayashi ◽  
Yasuo Niki ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Clinical Data ◽  
Weight Bearing ◽  
Mineral Density ◽  
Femorotibial Angle ◽  
Knee Oa ◽  
Bilateral Knee ◽  
Gait Parameters ◽  
The Relationship

Abstract Background: Although unloading of the joint is related to reduction of the local bone mineral density (BMD), little attention had been paid to the relationship between loading asymmetry and side-to-side difference of BMD in patients with bilateral knee osteoarthritis (OA). The aim of the present study was to evaluate and clarify the relationship between gait parameters and bone mineral density in those patients.Methods: A total of 36 knees in eighteen patients (mean age = 73.7 ± 6.3 years, mean body mass index = 26.7 ± 3.8 kg/m2) with bilateral medial knee OA were enrolled in the present study. All subjects performed relaxed standing and level walking at our gait laboratory after informed consent was obtained. First, ground reaction force was calculated on bilateral knees during standing. The knees in each patient were divided into Higher and Lower force side for the definition of dominant side limb. Second, gait parameters in each subject were obtained. To analyze the factors that affect the weight bearing distribution in both limbs, clinical data and biomechanical parameters were compared between knees. Clinical data included radiographic OA grade, femorotibial angle and BMD at the bilateral femoral neck.Results: Knees on Higher force side were significantly more extended than on Lower force side in standing (P=0.012) and knee excursion during weight acceptance phase in gait was significantly larger in Higher side than in Lower side (P=0.006), while the other parameters were not significantly different. As to the clinical data, Higher force side had greater BMD, compared to Lower force side. In terms of Kellgren-Lawrence scale and femorotibial angle on plain radiographs, there were no significant differences between Higher and Lower force side.Conclusions: Based on loading asymmetry in the present study, lower BMD was observed on Lower force side in patients with knee OA. Therefore, it is helpful for orthopedic surgeons to examine side-to-side differences of bone mineral density or extension limitation during standing for evaluation of the loading condition in patients with bilateral knee OA.

Sign in / Sign up

Export Citation Format

Share Document