Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition

AbstractA recent epidemiological study revealed that the highest prevalence of early knee osteoarthritis (OA) was observed in females aged ≥ 50 years. The major causal factor of early knee OA was sex. Despite the relevance of estrogen in evaluating chondral and bone metabolism in OA, it is not easily clinically monitored because irregular menstrual cycles induce unstable female hormone patterns during menopausal transitions. Anti-Mullerian hormone (AMH) has been found to be a new stable biomarker to predict menopause. This study aimed to investigate the association between menopausal transition and early knee OA by using serum biomarkers, with special focus on AMH. A total of 518 female volunteers who participated in the Iwaki cohort study were enrolled and divided into pre-menopause and post-menopause groups. Weight-bearing anterior–posterior knee radiographs were classified by Kellgren–Lawrence (KL) grade, and grade ≥ 2 was defined as radiographic knee OA. In participants with KL grades 0 and 1, early knee OA was defined by Luyten’s criteria. AMH, luteinizing hormone, follicle-stimulating hormone, estradiol (pg/ml), prolactin, and testosterone were measured on the female hormones. Bone mineral density at a distal radius was measured. The predictive power of female hormones for early knee OA was estimated by ROC analysis (comparison of area under curve, AUC) and regression analysis. Fifty-two participants (10.0%) were diagnosed with early knee OA and 204 (39.4%) with radiographic knee OA. In 393 (75.9%) females, menopause began. From the ROC analysis in pre-menopausal females, cutoff value of AMH for detecting early knee OA was 0.08 ng/ml (area under curve (AUC), 0.712; 95% CI, 0.527–0.897; p value, 0.025; odds ratio, 8.28). AUCs of other female hormones did not reach the level of AMH (range, 0.513 of prolactine to 0.636 of estradiol). Logistic regression analysis focusing on AMH reduction at menopausal transition showed that the related AMH below 0.08 ng/ml was significantly related to the presence of early knee OA (p = 0.035; odds ratio, 5.55). Reduced serum levels of AMH in middle-aged females were correlated with the presence of early knee OA, which might be a useful serum biomarker.

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Epidemiological study on the relationship among menopausal condition, bone fragility, and knee osteoarthritis

10.21203/rs.3.rs-84980/v1 ◽

2020 ◽

Author(s):

Eiji Sasaki ◽

Daisuke Chiba ◽

Seiya Ota ◽

Yuka Kimura ◽

Shizuka Sasaki ◽

...

Keyword(s):

Regression Analysis ◽

Knee Osteoarthritis ◽

Epidemiological Study ◽

Odds Ratio ◽

Weight Bearing ◽

Predictive Marker ◽

P Value ◽

Mineral Density ◽

High Turnover ◽

The Relationship

Abstract Background: Knee osteoarthritis (KOA) occurs more often in middle-aged females. While this age-group experiences comorbid osteoporosis with menopause, its influence on KOA has not been clarified. This epidemiological study aimed to investigate the relationship between menopausal conditions, bone mineral density (BMD), and KOA. Methods: A total of 518 female volunteers who participated in the Iwaki cohort study were enrolled and divided into groups (pre- and post-menopause). Antimullerian hormone (AMH) was measured as a predictive marker for menopause in the pre-menopausal subjects. Weight-bearing anterior-posterior knee radiographs were classified by Kellgren-Lawrence grade, and grade ≥ 2 was defined as definitive KOA (DKOA). Early KOA (EKOA) was defined by Luyten’s criteria, and BMD was measured at a distal radius. The relationship between menopausal condition, BMD, and KOA was analyzed by ROC and regression analysis. Results: Fifty-two participants (10.0%) were diagnosed with EKOA and 204 (39.4%) with DKOA. A total of 393 (75.9%) females began menopause, and the prevalence of DKOA was up to 48.1% and >12.0% in pre-menopause females (p < 0.001, Odds ratio: 6.79). From the ROC analysis in pre-menopausal females, cut-off value of AMH for detecting EKOA was 0.08 ng/ml (AUC: 0.712, p5%CI: 0.527 to 0.897, p-value: 0.025, Odds ratio: 8.28). Regression analysis showed that lower AMH was related to EKOA (p=0.035, Odds ratio: 5.55) and DKOA (p=0.032, Odds 1.59), and lower BMD and high turnover bone metabolism were correlated with DKOA. Conclusions: KOA increased after menopause and was correlated with lower BMD. Furthermore, reduction in AMH was a valuable biomarker for the detection of EKOA.

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Serum carotenoids and radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project

Public Health Nutrition ◽

10.1079/phn2001132 ◽

2001 ◽

Vol 4 (5) ◽

pp. 935-942 ◽

Cited By ~ 14

Author(s):

Anneclaire J De Roos ◽

Lenore Arab ◽

Jordan B Renner ◽

Neal Craft ◽

Gheorghe Luta ◽

...

Keyword(s):

Knee Osteoarthritis ◽

High Performance ◽

Conditional Logistic Regression ◽

Serum Levels ◽

Knee Oa ◽

Antioxidant Intake ◽

Matched Case ◽

Serum Carotenoids ◽

Β Carotene ◽

Radiographic Knee Osteoarthritis

AbstractObjective:Antioxidant intake has been associated with less progression of radiographic knee osteoarthritis (OA), but studies of carotenoid biomarkers and OA have not been done. We examined associations between serum concentrations of nine naturally occurring carotenoids and radiographic knee OA.Design:The study design was matched case–control. Sera were analysed by high-performance liquid chromatography for nine carotenoids: lutein, zeaxanthin, α- and β-cryptoxanthin, trans- and cis-lycopene, α-carotene, and trans- and cis-β-carotene. Conditional logistic regression was used to estimate the association between tertiles of each carotenoid and radiographic knee OA, independent of body mass index, education, serum cholesterol, and the other carotenoids.Setting:Johnston County, North Carolina, United States of America.Subjects:Two-hundred cases with radiographic knee OA (Kellgren–Lawrence grades ≥2) and 200 controls (Kellgren–Lawrence grade = 0) were randomly selected from the Johnston County Osteoarthritis Project, and were matched on age, gender and race.Results:Participants with serum levels of lutein or β-cryptoxanthin in the highest tertile were approximately 70% less likely to have knee OA than controls {odds ratio (OR) [95% confidence interval (CI)] = 0.28 [0.11, 0.73] and 0.36 [0.14, 0.95], respectively}. Those in the highest tertile of trans-β-carotene (OR = 6.40 [1.86, 22.1]) and zeaxanthin (OR = 3.06 [1.19, 7.85]) were more likely to have knee OA.Conclusions:While certain carotenoids may protect against knee OA, others may increase the odds of knee OA. Further study of carotenoids and knee OA are warranted before clinical recommendations about these substances and knee OA can be made.

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Change in self-reported outcomes and objective physical function over 7 years in middle-aged subjects with or at high risk of knee osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.074088 ◽

2007 ◽

Vol 67 (4) ◽

pp. 505-510 ◽

Cited By ~ 40

Author(s):

E M Roos ◽

A B Bremander ◽

M Englund ◽

L S Lohmander

Keyword(s):

High Risk ◽

Knee Osteoarthritis ◽

Physical Function ◽

Reference Group ◽

Population Based ◽

Observation Time ◽

Middle Aged ◽

Knee Oa ◽

Aged Subjects ◽

Over Time

Objective:In the present work, we describe the clinical course and predictors of change in self-reported outcomes and objectively assessed physical function over time in middle-aged subjects at high risk of, or with knee osteoarthritis (OA).Methods:We examined 259 subjects (mean (SD) age 52.6 (10.4)) at mean 18 and 25 years after previous meniscectomy and 50 population-based age- and sex-matched reference subjects with the Knee injury and Osteoarthritis Outcome Score (KOOS), one-leg hop for distance and number of knee-bendings in 30 s. Radiographic OA was defined as equivalent to Kellgren and Lawrence grade 2 or worse.Results:At first assessment, meniscectomised subjects reported worse pain, function and quality of life compared with the reference group (p<0.001). They also performed fewer knee-bendings per 30 s (27 vs 31, p = 0.02). The meniscectomised patients worsened over the 4–10-year observation time in all measured outcomes (p<0.001), and to a greater extent than the reference group in pain (−5, 95% CI −10 to 0) and one-leg hop (−11, 95% CI −18 to −3). Being a woman, or having radiographic knee OA, enhanced the worsening in self-reported and objectively assessed outcomes. Older age and a higher body mass index (BMI) influenced objectively assessed physical function, but not self-reported outcomes.Conclusion:Worsening over time in knee-related pain and function is greater in meniscectomised subjects compared with reference subjects. Rehabilitative efforts may be warranted in middle-aged meniscectomised patients, especially in women and those who have developed radiographic knee OA, who are at greater risk of worsening.

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A novel adipose hormone asprosin as a potential breast cancer marker

10.21203/rs.3.rs-897211/v1 ◽

2021 ◽

Author(s):

Sibel OZCAN ◽

Nilgun YILDIRIM ◽

Mesut YUR ◽

Mehmet Ridvan OZDEDE ◽

Mete OZCAN

Keyword(s):

Breast Cancer ◽

Odds Ratio ◽

Roc Analysis ◽

Gynecological Cancer ◽

Multivariable Analysis ◽

Serum Levels ◽

Regression Analyses ◽

Obese Adults ◽

Potential Association ◽

History Of

Abstract PurposeAsprosin is a recently discovered hormone released by white adipose tissue (WAT) that is typically significantly elevated in obese adults. Consequently, the adverse effects of increasing WAT in obesity during breast cancer (BC) development and progression have attracted interest of researchers and clinical practitioners. Thus, the aim of the present study was to determine whether the asprosin levels are associated with the probability of women having BC. MethodsThe study sample comprised of 45 female patients diagnosed with invasive BC and 42 healthy women that served as controls. Asprosin serum level was quantified in all subjects by ELISA, whereas serum levels of CEA and CA 15–3 were measured using an immunology analyzer. The potential association between asprosin and BC was examined through logistic regression analyses, while samples provided by BC patients were further subjected to ROC analysis to assess the diagnostic accuracy of asprosin. ResultsAsprosin levels were significantly higher in BC patients compared to healthy controls (2.38 ± 0.54 vs. 1.39 ± 0.53 ng/mL, p < 0.001). Multivariable analysis showed that the increased asprosin levels were associated with a significantly higher risk of breast cancer after adjustments for family history of breast and/or gynecological cancer, dyslipidemia, and BMI (odds ratio = 157.92; 95% confidence interval = 17.22−1447.96). When 1.78 ng/mL was adopted as the cut-off value, AUC, sensitivity, and specificity of asprosin for BC were 0.943, 91.1%, and 88.1%, respectively. ConclusionsOur findings demonstrate that asprosin is elevated in BC and can thus be an appropriate candidate for breast cancer diagnosis.

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Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114518001174 ◽

2018 ◽

Vol 120 (1) ◽

pp. 41-48 ◽

Cited By ~ 5

Author(s):

Shuang Zheng ◽

Bing Wang ◽

Weiyu Han ◽

Zhaohua Zhu ◽

Xia Wang ◽

...

Keyword(s):

Vitamin D ◽

Knee Osteoarthritis ◽

Vitamin D Deficiency ◽

Controlled Trial ◽

Serum Levels ◽

Vitamin D Supplementation ◽

Knee Oa ◽

Symptomatic Knee ◽

Post Hoc ◽

Metabolic Biomarkers

AbstractThe aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

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The Role of Pain Catastrophizing and Depression in the Outcomes of Physical Therapy in a Prospective Osteoarthritis Cohort

January 2018 - Pain Physician ◽

10.36076/ppj.2020/23/209 ◽

2020 ◽

Vol 2;23 (4;2) ◽

pp. 209-218

Author(s):

Aslı Çalıskan Uçkun

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Physical Therapy ◽

Knee Osteoarthritis ◽

Pain Catastrophizing ◽

Multivariate Logistic Regression Analysis ◽

Physical Therapy Modalities ◽

Multivariate Logistic Regression ◽

Knee Oa ◽

Poor Outcomes

Background: Physical modalities have been safely used for decades for pain relief and for reducing physical disability in the conservative treatment of knee osteoarthritis (OA). However, patients’ response to treatment is highly variable, which may be related to certain patient-related factors such as pain catastrophizing and depression. Objectives: This study aimed to evaluate the effects of pain catastrophizing and depression on physical therapy outcomes and to identify the baseline factors predictive of poor outcomes in patients with knee OA. Study Design: This research used a prospective, cohort, observational study design. Setting: The research took place in an outpatient physical therapy unit within a tertiary hospital in Ankara, Turkey. Methods: Eighty-nine patients with knee OA underwent 10 sessions of physical therapy. At baseline, depression and pain catastrophizing were evaluated using the Beck Depression InventoryII (BDI-II) and the Pain Catastrophizing Scale (PCS). The therapeutic efficacy of physical therapy was assessed based on the level of pain and disability using the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Changes in the VAS score and WOMAC were evaluated at 2 and 6 weeks following physical therapy. A multivariate logistic regression analysis was conducted to identify the predictors of poor outcomes. Results: Patients with low pain-catastrophizing and low depression scores tended to demonstrate better improvement at weeks 2 and 6. The results of a multivariate logistic regression analysis showed that the significant outcome predictor for both pain and function at week 6 was the baseline PCS score. The baseline depression score was not an independent predictor of a clinically poor outcome. Limitations: This study is limited owing to the combined use of several physical therapy modalities and short follow-up. Conclusions: This study suggests that the baseline PCS score is a predictive factor of poor response to physical therapy in patients with knee OA. Considering this factor before therapy and taking the necessary precautions may improve the outcomes of physical therapy. Key Words: Catastrophization, central nervous system sensitization, depression, disability evaluation, knee osteoarthritis, pain, physical therapy modalities, transcutaneous electric nerve stimulation.

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Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: the OFELY study

Arthritis Research & Therapy ◽

10.1186/s13075-019-2086-5 ◽

2020 ◽

Vol 22 (1) ◽

Cited By ~ 3

Author(s):

Jean-Charles Rousseau ◽

Marjorie Millet ◽

Martine Croset ◽

Elisabeth Sornay-Rendu ◽

Olivier Borel ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Odds Ratio ◽

Healthy Subjects ◽

Circulating Micrornas ◽

Expression Levels ◽

Knee Oa ◽

Serum Mirnas ◽

First Time ◽

Generation Sequencing

Abstract Objectives In the context of the scarcity of biomarkers for knee osteoarthritis (OA), we examined the associations of prevalent and incident OA with the expression levels of serum miRNAs in subjects with and without OA. Methods With a next-generation sequencing approach, we compared the miRome expression of 10 women with knee OA and 10 age-matched healthy subjects. By real-time qPCR, we analyzed the expression levels of 19 miRNAs at baseline selecting 43 women with prevalent knee OA (Kellgren Lawrence score of 2/3), 23 women with incident knee OA over a 4-year follow-up and 67 healthy subjects without prevalent or incident OA matched for age and body mass index. Results Serum miR-146a-5p was significantly increased in the group of prevalent knee OA compared with controls (relative quantification (RQ); median [Interquartile range] 1.12 [0.73; 1.46] vs 0.85 [0.62; 1.03], p = 0.015). The likelihood of prevalent knee OA was significantly increased (odds ratio [95% confidence interval (CI)] 1.83 [1.21–2.77], p = 0.004) for each quartile increase in serum miR-146a-5p. The women with miR-146a-5p levels above the median (0.851) had a higher risk of prevalent knee OA compared to those below the median [95% CI] 4.62 [1.85–11.5], p = 0.001. Moreover, we found a significant association between the baseline level of serum miR-186-5p and the risk of incident knee OA (Q4 vs Q1–3; odds ratio [95% CI] 6.13 [1.14–32.9], p = 0.034). Conclusion We showed for the first time that miR-146a-5p and miR-186-5p are significantly associated with prevalent and incident knee OA, respectively.

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Mild knee osteoarthritis predicts dissatisfaction after total knee arthroplasty: a prospective study of 186 patients aged 65 years or less with 2-year follow-up

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04543-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sanni Leppänen ◽

Mika Niemeläinen ◽

Heini Huhtala ◽

Antti Eskelinen

Keyword(s):

Total Knee Arthroplasty ◽

Logistic Regression ◽

Regression Analysis ◽

Knee Osteoarthritis ◽

Persistent Pain ◽

Younger Patients ◽

Knee Oa ◽

Increased Risk ◽

Total Knee

Abstract Background and aims The incidence of total knee arthroplasty (TKA) is increasing, especially among younger working-age patients. However, dissatisfaction rates in this population are higher than among older patients. The aim of this study was to assess the rates of dissatisfaction and persistent pain after TKA and to evaluate those factors that predict these outcomes. Material and methods In total, 186 patients undergoing unilateral TKA aged 65 years or less were enrolled into this prospective observational study with 2-year follow-up. To assess the outcome, the visual analogue scales regarding satisfaction and persistent pain at rest and during exercise were used. In addition, the association between patients´ demographics, radiographic severity of knee osteoarthritis (OA), patient-reported outcome measures (PROMs) and dissatisfaction and persistent pain were tested by univariate logistic regression analysis. Mild OA was defined as Kellgren-Lawrence (KL) grade 2 and severe OA as KL grade 3–4. Furthermore, multiple logistic regression analysis was also conducted to test statistically significant relations. Results After 2 years, 12 % (n = 23) of patients were dissatisfied with the outcome of TKA, 27 % (n = 50) reported persistent pain during exercise and 10 % (n = 18) at rest. Patients with mild knee OA were significantly more dissatisfied (28.6 %) than patients with more severe OA (8.7 %) (p = 0.003). Younger patients had an increased risk for both dissatisfaction and persistent pain. Apart from KOOS Quality of Life, poor preoperative KOOS subscores were also predictive for these outcomes. Conclusion Mild radiographic knee OA was the main predicting factor for dissatisfaction after TKA. Thus, performing TKA for such patients should be carefully considered. Furthermore, these patients should be informed about the increased risk for dissatisfaction and the same seems to apply to younger patients. Interestingly, when TKA is performed for patients with more severe knee OA, the satisfaction rates seem to be somewhat higher than those previously reported. Trial registration The study was retrospectively registered with ClinicalTrials.gov (registration number NCT03233620) on 28 July 2017.

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Serum Biomarkers of Inflammation and Turnover of Joint Cartilage Can Help Differentiate Psoriatic Arthritis (PsA) Patients from Osteoarthritis (OA) Patients

Diagnostics ◽

10.3390/diagnostics11010052 ◽

2020 ◽

Vol 11 (1) ◽

pp. 52

Author(s):

Michał Waszczykowski ◽

Anna Fabiś-Strobin ◽

Igor Bednarski ◽

Aleksandra Lesiak ◽

Joanna Narbutt ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Odds Ratio ◽

Multivariate Logistic Regression Analysis ◽

Serum Levels ◽

Serum Biomarkers ◽

Control Group ◽

Healthy Individuals ◽

Joint Cartilage ◽

Multivariate Logistic Regression ◽

Knee Oa

The aim of this study was to find characteristic biomarkers in the serum of patients with osteoarthritis (OA) and psoriatic arthritis (PsA) responsible for inflammation and destruction of joint cartilage, which could differentiate these two diseases. The study included 67 people: 22 patients with knee OA, 22 patients with PsA, and 23 individuals who were the control group of healthy individuals (HC). The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum were determined. Among the OA and PsA patients group, the radiological assessment and clinical assessment were also performed. The concentration of 7 out of 8 of examined biomarkers (except MMP-1) was statistically significantly higher in the serum of patients with OA and PsA than in the control group. Compering OA and PsA groups only, the serum PG-AG level in OA patients was statistically significantly higher than in PsA patients (p < 0.001). The results of univariate and multivariate logistic regression analysis comparing OA and PsA biomarker serum levels identified PG-AG and COMP as markers that are significantly different between patients with OA and PsA (odds ratio 0.995 and 1.003, respectively). The ROC curve constructed using the model with age showed PG-AG and COMP had an AUC of 0.907. The results of this study show that COMP and PG-AG may be sensitive markers differentiating patients with osteoarthiritis from psoriatic arthritis.

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Serum Leptin and Resistin Levels in Knee Osteoarthritis—Clinical and Radiologic Links: Towards Precise Definition of Metabolic Type Knee Osteoarthritis

Biomedicines ◽

10.3390/biomedicines9081019 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1019

Author(s):

Sevdalina Nikolova Lambova ◽

Tsvetelina Batsalova ◽

Dzhemal Moten ◽

Stela Stoyanova ◽

Elenka Georgieva ◽

...

Keyword(s):

Risk Factor ◽

Knee Osteoarthritis ◽

Clinical Characteristics ◽

Serum Levels ◽

Precise Definition ◽

Control Group ◽

Serum Leptin ◽

Mean Values ◽

Knee Oa ◽

Definition Of

Obesity is considered a major risk factor for the development and progression of knee osteoarthritis (OA). Apart from the mechanical effect of obesity via increase in mechanical overload of weight-bearing joints, an association with hand OA has been observed. There has been increasing interest in the role of adipokines in the pathogenesis of OA in the recent years. It has been suggested that their systemic effects link obesity and OA. In this regard, the aim of the current study was measurement and analysis of serum levels of leptin and resistin in patients with knee OA with different body mass index (BMI). Seventy-three patients with primary symptomatic knee OA at the age between 35 and 87 years (mean age 66 years) were included in the study (67 women and 6 men). The patients were from 2nd to 4th radiographic stage according to Kellgren–Lawrence scale. 43 patients were with concomitant obesity (BMI ≥ 30 kg/m2, mean values 38.34 ± 8.20) and 30 patients with BMI < 30 kg/m2 (mean values 25.07 ± 2.95). Eleven individuals with different BMIs, including cases with obesity but without radiographic knee OA, were examined as a control group. Serum levels of leptin and resistin were measured via ELISA method. In patients with knee OA and BMI ≥ 30 kg/m2, serum levels of leptin (39.546 ± 12.918 ng/mL) were significantly higher as compared with healthy individuals (15.832 ± 16.531 ng/mL, p < 0.05) and the patients with low BMI (p < 0.05). In patients with BMI < 30 kg/m2 the levels of leptin (13.010 ± 10.94 ng/mL) did not differ significantly from the respective values in the control group (p = 0.48). Serum levels of resistin were also higher in knee OA patients in comparison with healthy controls, but the difference was statistically significant only for patients with high BMI (2.452 ± 1.002 ng/mL in the group with BMI ≥ 30 kg/m2; 2.401 ± 1.441 ng/mL in patients with BMI < 30 kg/m2; 1.610 ± 1.001 ng/mL in the control group, p < 0.05). A correlation was found between the serum levels of leptin and radiographic stage of OA, i.e., higher leptin levels were present in the more advanced 3rd and 4th radiographic stage, while for resistin a correlation was observed in the patient subgroup with BMI < 30 kg/m2. Serum leptin and resistin levels and clinical characteristics were analyzed in patients with different clinical forms of OA. Novel clinical correlations have been found in the current study in patients with isolated knee OA vs. cases with presence of other disease localizations. It has been observed that patients with isolated knee OA were significantly younger and had higher BMI as compared with cases in whom OA is combined with other localizations i.e., spondyloarthritis ± presence of hip OA and with generalized OA. This supports the hypothesis that presence of obesity promotes earlier development of knee OA as an isolated localization of the disease in younger patients before appearance of osteoarthritic changes at other sites. The levels of leptin and resistin in isolated knee OA were also higher. Serum levels of leptin and resistin in combination with patients’ clinical characteristics suggest existence of different clinical and laboratory profile through which more precise definition of metabolic phenotype of knee OA would be possible. Considering the fact that obesity is a modifiable risk factor that has an impact on progression of knee OA, different approaches to influence obesity may offer potential for future disease-modifying therapeutic interventions.

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