Analysis of spatial osteochondral heterogeneity in advanced knee osteoarthritis exposes influence of joint alignment

2020 ◽  
Vol 12 (562) ◽  
pp. eaba9481 ◽  
Author(s):  
Sophie Haberkamp ◽  
Tamás Oláh ◽  
Patrick Orth ◽  
Magali Cucchiarini ◽  
Henning Madry
Keyword(s):  
Weight Loss ◽  
Structural Changes ◽  
Scientific Basis ◽  
Strong Correlations ◽  
Varus Knee ◽  
Varus Malalignment ◽  
Compensatory Mechanisms ◽  
Site Specific ◽  
Knee Oa ◽  
Specific Effects

Osteoarthritis (OA) is considerably affected by joint alignment. Here, we investigate the patterns of spatial osteochondral heterogeneity in patients with advanced varus knee OA together with clinical data. We report strong correlations of osteochondral parameters within individual topographical patterns, highlighting their fundamental and location-dependent interactions in OA. We further identify site-specific effects of varus malalignment on the lesser loaded compartment and, conversely, an unresponsive overloaded compartment. Last, we trace compensatory mechanisms to the overloaded subarticular spongiosa in patients with additional high body weight. We therefore propose to consider and to determine axial alignment in clinical trials when selecting the location to assess structural changes in OA. Together, these findings broaden the scientific basis of therapeutic load redistribution and weight loss in varus knee OA.

Relationship Between Low Bone Mineral Density and Varus Deformity in Postmenopausal Women with Knee Osteoarthritis

2009 ◽  
Vol 36 (3) ◽  
pp. 592-597 ◽  
Author(s):  
YASUSHI AKAMATSU ◽  
NAOTO MITSUGI ◽  
NAOYA TAKI ◽  
RYOHEI TAKEUCHI ◽  
TOMOYUKI SAITO
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Knee Osteoarthritis ◽  
Structural Changes ◽  
Tibial Plateau ◽  
Varus Deformity ◽  
Varus Knee ◽  
Mineral Density ◽  
Femorotibial Angle ◽  
Knee Oa

Objective.To assess the relationship between bone mineral density (BMD) and varus deformity arising from bone structural changes caused by knee osteoarthritis (OA) in postmenopausal women.Methods.This cross-sectional study involved 135 consecutive postmenopausal female patients who had varus knee OA and a Kellgren-Lawrence grade ≥ 2. Knee radiographs were obtained with the patient standing on one leg, and subjects were classified into 3 tertile groups according to femorotibial angle, which was taken as a measure of varus knee OA severity. We also measured the 3 subangles that make up the femorotibial angle, and focused on the varus inclination of the tibial plateau. BMD was measured in the lumbar spine, femoral neck, and medial and lateral tibial condyles using dual-energy X-ray absorptiometry. Differences between femorotibial angle tertile groups were assessed, and associations between femorotibial sub-angles and BMD values at various points were evaluated.Results.After adjustment for age and body mass index, there was no significant association between the varus inclination of the tibial plateau and lumbar spine BMD. A weak but statistically significant negative correlation existed between varus inclination of the tibial plateau and BMD at the ipsilateral proximal femur and lateral tibial condyle.Conclusion.Varus inclination of the tibial plateau was significantly more severe in the femorotibial angle tertile 3 group, and in patients with lower BMD in the ipsilateral lower limb. Varus knee OA may result not only from cartilage loss but also from structural changes of the bone.

Trials Back Weight Loss in Obese Knee OA Patients

2006 ◽  
Vol 39 (17) ◽  
pp. 16
Author(s):  
BRUCE JANCIN
Keyword(s):  
Weight Loss ◽  
Knee Oa

Abstract 3635: Weight Loss Reverses Left Ventricular Structural Changes In Subjects With Severe Uncomplicated Obesity. A One year Follow Up Study.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Oliver J Rider ◽  
Jane M Francis ◽  
Mohammed K Ali ◽  
Monique R Robinson ◽  
Stefan Neubauer
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Structural Changes ◽  
Total Body Weight ◽  
Cardiac Risk ◽  
Left Ventricular ◽  
Cardiac Risk Factors ◽  
Co Morbidity ◽  
Lv Mass ◽  
One Year

Objective Obesity has been linked to a spectrum of cardiovascular abnormalities from subclinical changes in cardiac structure to overt heart failure. Uncomplicated obesity (i.e. obesity without any other co-morbidity or cardiovascular risk factors) has been shown to cause increased LV mass and LV dilatation. Our hypothesis was that these changes are, at least in part, reversible following significant weight loss over one year. Method Forty-one obese (BMI 37.7 ± 7.4 SD) and 12 age, sex matched controls (BMI 21.6 ± 1.8 SD) with no identifiable cardiac risk factors underwent cardiac MR imaging for the assessment of LV Mass (g), LV end-diastolic volume (EDV; ml), stroke volume (SV; ml) and LV EF (%). Fourteen obese subjects underwent repeat imaging after a one year period of weight loss, averaging 14.6 ± 11.5 % total body weight. Results Obesity per se was associated with elevated LV mass (125 ± 27 vs 89 ± 23g; p<0.001), LV mass indexed to height (74.4 ± 14.3 vs 52.3 ± 11.4g/m; p<0.001) and EDV (147 ± 28 vs 119 ± 24 ml; p<0.001). ESV and SV were also elevated in obesity (47 ± 12 vs 39 ± 12ml; p=0.05, and 100 ± 14 vs 80 ± 18 ml; p<0.001, respectively). LV EF was similar between groups (p=0.83). After weight loss, there was a significant reduction in LV mass (by 16 ± 11g; 135 ± 31 vs 119 ± 28g; p<0.001), LV mass indexed to height (76.4 ± 15.7 vs 68.9 ± 12 g/m; p<0.001). EDV and ESV were significantly smaller after weight loss (146 ± 25 vs 133 ± 23 ml; p<0.001, and 43 ± 12 vs 41 ± 10 ml; p<0.001 respectively). LV EF and SV did not change significantly. Conclusion In subjects with obesity in the absence of identifiable cardiac risk factors, LV hypertrophy and LV dilatation were partially reversible after a one year period of weight loss.

scholarly journals Site-specific effects on respiratory rhythm and pattern of ibotenic acid injections in the pontine respiratory group of goats

2010 ◽  
Vol 109 (1) ◽  
pp. 171-188 ◽  
Author(s):  
J. M. Bonis ◽  
S. E. Neumueller ◽  
K. L. Krause ◽  
T. Kiner ◽  
A. Smith ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Respiratory Rhythm ◽  
Ibotenic Acid ◽  
Pattern Generation ◽  
Respiratory Pattern ◽  
Breathing Patterns ◽  
Site Specific ◽  
Specific Effects ◽  
Tegmental Nuclei ◽  
Pontine Respiratory Group

To probe further the contributions of the rostral pons to eupneic respiratory rhythm and pattern, we tested the hypothesis that ibotenic acid (IA) injections in the pontine respiratory group (PRG) would disrupt eupneic respiratory rhythm and pattern in a site- and state-specific manner. In 15 goats, cannulas were bilaterally implanted into the rostral pontine tegmental nuclei (RPTN; n = 3), the lateral (LPBN; n = 4) or medial parabrachial nuclei (MPBN; n = 4), or the Kölliker-Fuse nucleus (KFN; n = 4). After recovery from surgery, 1- and 10-μl injections (1 wk apart) of IA were made bilaterally through the implanted cannulas during the day. Over the first 5 h after the injections, there were site-specific ventilatory effects, with increased ( P < 0.05) breathing frequency in RPTN-injected goats, increased ( P < 0.05) pulmonary ventilation (V̇i) in LPBN-injected goats, no effect ( P < 0.05) in MPBN-injected goats, and a biphasic V̇i response ( P < 0.05) in KFN-injected goats. This biphasic response consisted of a hyperpnea for 30 min, followed by a prolonged hypopnea and hypoventilation with marked apneas, apneusis-like breathing patterns, and/or shifts in the temporal relationships between inspiratory flow and diaphragm activity. In the awake state, 10–15 h after the 1-μl injections, the number of apneas was greater ( P < 0.05) than during other studies at night. However, there were no incidences of terminal apneas. Breathing rhythm and pattern were normal 22 h after the injections. Subsequent histological analysis revealed that for goats with cannulas implanted into the KFN, there were nearly 50% fewer neurons ( P < 0.05) in all three PRG subnuclei than in control goats. We conclude that in awake goats, 1) IA injections into the PRG have site-specific effects on breathing, and 2) the KFN contributes to eupneic respiratory pattern generation.

scholarly journals Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e024065 ◽  
Author(s):  
Henrik Gudbergsen ◽  
Marius Henriksen ◽  
Eva Ejlersen Wæhrens ◽  
Anders Overgaard ◽  
Henning Bliddal ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Knee Osteoarthritis ◽  
Controlled Trial ◽  
Single Centre ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Knee Oa ◽  
Parallel Group ◽  
Pain Subscale

IntroductionWith an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA.Methods and analysis150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week −8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52.Ethics and disseminationThe trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals.Trial registration numbers2015-005163-16,NCT02905864, U1111-1171-4970Based on protocol versionV.6; 30 January 2017, 15:30 hours

scholarly journals The Oxidative Stress in Knee Osteoarthritis Patients. An Attempt of Evaluation of Possible Compensatory Effects Occurring in the Disease Development

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 150 ◽  
Author(s):  
Marek Paździor ◽  
Małgorzata Kiełczykowska ◽  
Jacek Kurzepa ◽  
Dorota Luchowska-Kocot ◽  
Joanna Kocot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Total Antioxidant Status ◽  
Therapeutic Agents ◽  
Disease Development ◽  
Enzymatic Antioxidants ◽  
Compensatory Mechanisms ◽  
Knee Oa ◽  
Total Antioxidant ◽  
Antioxidant Supplements

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 ± 0.53 vs. 4.70 ± 0.60), with this effect being more significant in OA females (4.31 ± 0.51 vs. 5.02 ± 0.54). GPx was depressed in all OA patients (518 ± 176 vs. 675 ± 149). In both genders, GPx was decreased, significantly in males (482 ± 185 vs. 715 ± 105). SOD was decreased in all OA patients (109 ± 32 vs. 127 ± 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6–31.6) vs. 38.5 (27.9–46.6)) and in OA men it increased (26.9 (23.3–46.5) vs. 14.0 (7.0–18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.

scholarly journals MO046NON-ACTIVATABLE MUTANT OF INHIBITOR OF KAPPA B KINASE α (IKKα) EXERTS SITE-SPECIFIC EFFECTS ON ATHEROSCLEROSIS

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i48-i48
Author(s):  
Pathricia V. Tilstam ◽  
Wendy Theelen ◽  
Setareh Alampour-Sarabi ◽  
Lukas Pawig ◽  
Yaw Asare ◽  
...  
Keyword(s):  
Site Specific ◽  
Specific Effects
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