Genetic,clinical and radiographic signs in knee osteoarthritis susceptibility

Introduction

Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals.

Methods

In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis.

Results

In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features.

Conclusions

This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.     

Extracorporeal shockwave therapy in osteoporotic osteoarthritis of the knee in rats: an experiment in animals

Introduction

This study investigated the effectiveness of extracorporeal shockwave therapy (ESWT) in osteoporotic (OP) osteoarthritis (OA) of rat knee.

Methods

Fifty-six rats were divided into seven groups including sham, OA, OP, OA + OP, OA + ESWT, OP + ESWT, and OA + OP + ESWT groups. The evaluations included gross pathology, bone mineral density (BMD), micro-computed tomography (micro-CT) scan, bone-strength test, histopathologic examination, and immunohistochemical analysis.

Results

On gross pathology, group OA + OP showed larger areas of osteoarthritic changes than did groups OA and OP, as compared with the sham group. BMD and bone strength significantly decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly improved BMD and bone-strength changes. On micro-CT scan, the subchondral plate thickness significantly decreased, and the bone porosity increased in groups OA, OP, and OA + OP, and ESWT significantly improved the changes in subchondral-plate thickness and bone porosity. In histopathologic examination, Mankin score and safranin O score significantly increased in groups OA and group OA + OP, but not in group OP relative to the sham group, and ESWT significantly improved the changes. In immunohistochemical analysis, Dickkopf-1 (DKK-1) significantly increased, but vessel endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and bone morphogenetic protein 2 (BMP-2) decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly reversed the changes.

Conclusions

Osteoporosis increased the severity of cartilage damage in osteoarthritis of the knee. ESWT showed effectiveness in the reduction of osteoporotic osteoarthritis of the knee in rats.     

Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis in the Johnston County Osteoarthritis Project

Introduction  

Lead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee.     

Biomechanical factors and physical examination findings in osteoarthritis of the knee: associations with tissue abnormalities assessed by conventional radiography and high-resolution 3.0 Tesla magnetic resonance imaging

Introduction

We aimed to explore the associations between knee osteoarthritis (OA)-related tissue abnormalities assessed by conventional radiography (CR) and by high-resolution 3.0 Tesla magnetic resonance imaging (MRI), as well as biomechanical factors and findings from physical examination in patients with knee OA.

Methods

This was an explorative cross-sectional study of 105 patients with knee OA. Index knees were imaged using CR and MRI. Multiple features from CR and MRI (cartilage, osteophytes, bone marrow lesions, effusion and synovitis) were related to biomechanical factors (quadriceps and hamstrings muscle strength, proprioceptive accuracy and varus-valgus laxity) and physical examination findings (bony tenderness, crepitus, bony enlargement and palpable warmth), using multivariable regression analyses.

Results

Quadriceps weakness was associated with cartilage integrity, effusion, synovitis (all detected by MRI) and CR-detected joint space narrowing. Knee joint laxity was associated with MRI-detected cartilage integrity, CR-detected joint space narrowing and osteophyte formation. Multiple tissue abnormalities including cartilage integrity, osteophytes and effusion, but only those detected by MRI, were found to be associated with physical examination findings such as crepitus.

Conclusion

We observed clinically relevant findings, including a significant association between quadriceps weakness and both effusion and synovitis, detected by MRI. Inflammation was detected in over one-third of the participants, emphasizing the inflammatory component of OA and a possible important role for anti-inflammatory therapies in knee OA. In general, OA-related tissue abnormalities of the knee, even those detected by MRI, were found to be discordant with biomechanical and physical examination features.     

Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis

Introduction

Collagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis and, second, to explore a synergetic effect with hyaluronan (HA).

Methods

Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 was also analyzed immunohistochemically. A Tukey''s honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.

Results

All treatment groups exhibited slightly higher resistance to the progression of osteoarthritis than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected.

Conclusion

Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.     

Breastfeeding and Bone Mass at the Ages of 18 and 30: Prospective Analysis of Live Births from the Pelotas (Brazil) 1982 and 1993 Cohorts

Objective

To evaluate the effect of total breastfeeding, breastfeeding duration and type of breastfeeding at 3 months of age on bone mass at 18 and 30 years.

Study Design

A prospective, longitudinal study was conducted with two birth cohorts (1982 and 1993) in Pelotas, Southern Brazil. Measurements of bone mineral content (BMC) and bone mineral density (BMD) at 18 and 30 years of age were obtained by dual-energy X-ray absorptiometry (DXA). Information on breastfeeding was collected during the first 4 years of life. Analyses were performed by linear regression and stratified by sex.

Results

A total of 1109 and 3226 participants provided complete information on breastfeeding in early life and bone mass at 18 and 30 years, respectively. No association between breastfeeding and bone mass was observed in women at both ages nor among men at age 30. Among men at the age of 18, BMC and BMD were higher among those breastfed regardless of duration (p=0.032 and p=0.043, respectively).

Conclusions

Despite a very weak positive effect of breastfeeding (yes/no) on BMC and BMD at age 18 in men, most findings pointed to a lack of association between breastfeeding and bone mass until young adulthood.     

Bone related health status in adolescent cyclists

Purpose

To describe bone status and analyse bone mass in adolescent cyclists.

Methods

Male road cyclists (n = 22) who had been training for a minimum of 2 years and a maximum of 7 years with a volume of 10 h/w, were compared to age-matched controls (n = 22) involved in recreational sports activities. Subjects were divided in 2 groups based on age: adolescents under 17 yrs (cyclists, n = 11; controls, n = 13) and over 17 yrs (cyclists, n = 11; controls, n = 9). Peak oxygen uptake (VO₂max) was measured on a cycloergometer. Whole body, lumbar spine, and hip bone mineral content (BMC), density (BMD) and bone area were assessed using dual x-ray absorptiometry (DXA). Volumetric BMD (vBMD) and bone mineral apparent density (BMAD) were also estimated.

Results

The BMC of cyclists was lower for the whole body, pelvis, femoral neck and legs; BMD for the pelvis, hip, legs and whole body and legs bone area was lower but higher in the hip area (all, P≤0.05) after adjusting by lean mass and height. The BMC of young cyclists was 10% lower in the leg and 8% higher in the hip area than young controls (P≤0.05). The BMC of cyclists over 17 yrs was 26.5%, 15.8% and 14.4% lower BMC at the pelvis, femoral neck and legs respectively while the BMD was 8.9% to 24.5% lower for the whole body, pelvis, total hip, trochanter, intertrochanter, femoral neck and legs and 17.1% lower the vBMD at the femoral neck (all P≤0.05). Grouped by age interaction was found in both pelvis and hip BMC and BMD and in femoral neck vBMD (all P≤0.05).

Conclusion

Cycling performed throughout adolescence may negatively affect bone health, then compromising the acquisition of peak bone mass.     

Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

Background

The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain.

Objective

To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF).

Methods

In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness.

Results

Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models.

Conclusion

Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass.     

Prevalence of Radiographic Osteoarthritis of the Knee and Its Relationship to Self-Reported Pain

Background and Aim

Osteoarthritis (OA) of the knee is one of the most common skeletal disorders, yet little data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic OA of the knee, and its relationship to self-reported pain in a Vietnamese population.

Methods

The study was based on a sample of 170 men and 488 women aged ≥40 years who were randomly sampled from the Ho Chi Minh City (Vietnam). Radiographs of the knee were graded from 0 to 4 according to the Kellgren and Lawrence scale. Osteoarthritis was defined as being present in a knee if radiographic grades of 2 or higher were detected. Knee pain and symptoms were ascertained by direct interview using a structured questionnaire.

Results

The point prevalence of radiographic OA of the knee was 34.2%, with women having higher rate than men (35.3% vs 31.2%). The prevalence of knee OA increased with advancing age: 8% among those aged 40–49 years, 30% in those aged 50–59 years, and 61.1% in those aged ≥60 years. Greater BMI was associated with higher risk of knee OA. Self-reported knee pain was found in 35% of men and 62% of women. There was a statistically significant association between self-reported knee pain and knee OA (prevalence ratio 3.1; 95% CI 2.0 to 4.6).

Conclusions

These data indicate that approximately a third of Vietnamese men and women have radiographic OA in the knee, and that self-reported knee pain may be used as an indicator of knee osteoarthritis.     

Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development

Introduction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be important in the development of inflammatory models of rheumatoid arthritis and there is encouraging data that its blockade may have clinical relevance in patients with rheumatoid arthritis. The aims of the current study were to determine whether GM-CSF may also be important for disease and pain development in a model of osteoarthritis.

Methods

The role of GM-CSF was investigated using the collagenase-induced instability model of osteoarthritis. We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease development (both early and late) was evaluated by histology and knee pain development was measured by assessment of weight distribution.

Results

In the absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated neoepitope expression at week 2 post disease induction, and less cartilage damage at week 6. GM-CSF was absolutely required for pain development. Therapeutic neutralization of GM-CSF not only abolished the pain within 3 days but also led to significantly reduced cartilage damage.

Conclusions

GM-CSF is key to the development of experimental osteoarthritis and its associated pain. Importantly, GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly and completely abolished existing arthritic pain and suppressed the degree of arthritis development. Our results suggest that it would be worth exploring the importance of GM-CSF for pain and disease in other osteoarthritis models and perhaps clinically for this form of arthritis.     

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis

Introduction

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.

Methods

Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).

Results

sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.

Conclusions

These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.     

Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism

Objective

Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.

Methods

OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.

Results

Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2–3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.

Conclusion

The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA.     

Quantification of the whole-body burden of radiographic osteoarthritis using factor analysis

Introduction  

Although osteoarthritis (OA) commonly involves multiple joints, no widely accepted method for quantifying whole-body OA burden exists. Therefore, our aim was to apply factor analytic methods to radiographic OA (rOA) grades across multiple joint sites, representing both presence and severity, to quantify the burden of rOA.     

The Benefit of Bone Health by Drinking Coffee among Korean Postmenopausal Women: A Cross-Sectional Analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys

Purpose

Although the concern about coffee-associated health problems is increasing, the effect of coffee on osteoporosis is still conflicting. This study aimed to determine the relationship between coffee consumption and bone health in Korean postmenopausal women.

Methods

A population-based, cross-sectional study was performed using a nationally representative sample of the Korean general population. All 4,066 postmenopausal women (mean age 62.6 years) from the fourth and fifth Korean National Health and Nutrition Examination Survey (2008–2011), who completed the questionnaire about coffee consumption and had data of dual-energy X-ray absorptiometry (DXA) examination. Bone mineral density (BMD) was measured using DXA at the femoral neck and lumbar spine and osteoporosis was defined by World Health Organization T-score criteria in addition to self-report of current anti-osteoporotic medication use.

Results

After adjusting for various demographic and lifestyle confounders (including hormonal factors), subjects in the highest quartile of coffee intake had 36% lower odds for osteoporosis compared to those in the lowest quartile (Adjusted odds ratio [aOR] = 0.64; 95% confidence interval [CI], 0.43–0.95; P for trend = 0.015). This trend was consistent in osteoporosis of lumbar spine and femoral neck (aOR = 0.65 and 0.55; P for trend = 0.026 and 0.003, respectively). In addition, age- and body mass index (BMI)-adjusted BMD of the femoral neck and lumbar spine increased with higher coffee intake (P for trend = 0.019 and 0.051, respectively).

Conclusions

Coffee consumption may have protective benefits on bone health in Korean postmenopausal women in moderate amount. Further, prospective studies are required to confirm this association.     

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker - longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative

Introduction

Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN).

Methods

A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume).

Results

This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume.

Conclusion

Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.     

Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

Background

Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.

Methods

We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.

Results

OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.

Conclusions

Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.     

The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study

Introduction

Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP).

Methods

This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed.

Results

Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P = 0.007) and total (P <0.001) scores as well as higher VAS pain score (P = 0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P = 0.006) and lateral (P = 0.023) compartments, and presence of meniscal tears in the lateral compartment (P = 0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P = 0.032, P = 0.027, respectively).

Conclusions

In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01733277","term_id":"NCT01733277"}}NCT01733277. Registered 16 November 2012.     

Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain

Background

Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ) “super-healer” mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant.

Methodology

The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ “super-healer” mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints.

Principal Findings

Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair.

Conclusion and Significance

The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow.     

Clinical features of symptomatic patellofemoral joint osteoarthritis

Introduction

Patellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting.

Methods

This was a population-based cross-sectional study of 745 adults aged ≥50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: ''any OA'' and ''moderate to severe OA''. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets.

Results

Distinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA.

Conclusions

Early isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.     

Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis by Regulating Nitric Oxide and Inflammatory Cytokines

Objective

To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).

Materials and Methods

OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.

Results

Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.

Conclusion

CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.