"You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis.

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â€‹= â€‹17 groups) and one-on-one interviews (n â€‹= â€‹3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â€‹% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.

3D analysis and grading of calcifications from ex vivo human meniscus.

OBJECTIVE: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (µCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. METHOD: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with µCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D µCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CVM) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity. RESULTS: 3D µCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CVM that is 20.3 times higher (95% CI 13.3-30.5) than in the previous grade. However, there was no apparent difference in CVM between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades. CONCLUSIONS: 3D µCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1-2), and 2) with large to widespread calcifications (calcification grades 3-5).

The genetic contribution to hand osteoarthritis.

OBJECTIVE: To estimate the genetic contribution to doctor-diagnosed hand osteoarthritis (OA). METHODS: Using data from the Swedish Twin Registry and National Patient Register, we conducted a 20-year population-based longitudinal cohort study including 59,970 twins aged 35 years or older. We studied inpatient and outpatient doctor-diagnosed hand OA using ICD-10 codes from 1997 until 2016, including both the distal/proximal interphalangeal (DIP/PIP) joints and/or the first carpometacarpal (CMC-1) joints. We calculated intra-pair correlation, estimated the heritability (i.e., the percentage variation in hand OA that can be explained by genetic factors) as well as a genetic risk. RESULTS: Among 59,970 included persons, 936 had a hand OA diagnosis registered during the study period. The heritabilities of hand OA (any joint), CMC-1 OA and DIP/PIP OA were ∼87%, 86% and 48%, respectively, yet the two latter should be interpreted with care due to low numbers. Hand OA in any joint in both twins in a pair occurred more frequently in identical twins (54/554 = 9.7%, intra-pair correlation = 0.54, 95% CI = 0.44-0.63) than in fraternal twins (18/1,246 = 1.4%, intra-pair correlation = 0.10, 95% CI = -0.01-0.22). Identical twins who were diagnosed with hand OA in any joint had a far higher risk than fraternal twins with hand OA to also have their co-twin diagnosed with hand OA in any joint (Hazard Ratio = 6.98, 95% CI = 3.08-15.45). CONCLUSION: The genetic contribution to hand OA is high and likely varying between 48% and 87%. Potential differential heritability by hand OA phenotypes should be further explored.

Opioid use prior to total knee replacement: comparative analysis of trends in England and Sweden.

OBJECTIVES: To describe and compare trends in the frequency of opioid prescribing/dispensing in English and Swedish patients with osteoarthritis prior to total knee replacement (TKR). METHODS: 49,043 patients from an English national database (Clinical Practice Research Datalink) and 5,955 patients from the Swedish Skåne Healthcare register undergoing TKR between 2015 and 2019 were included, alongside 1:1 age-, sex-, and practice (residential area) matched controls. Annual prevalence and prevalence rates ratio (PRR) of opioid prescribing/dispensing (any, by strength) in the 10 years prior to TKR (or matched index date for controls) were estimated using Poisson regression. RESULTS: In England and Sweden, the prevalence of patients with osteoarthritis receiving any opioid prior to TKR increased towards the date of surgery from 24% to 44% in England and from 16% to 33% in Sweden. Prescribing in controls was stable, resulting in an increasing PRR (1.6-2.7) between 10 and 1 years prior to index date in both countries. No relevant cohort or period effect was observed in either country. Prevalence of opioid prescribing was higher in English cases and controls; weaker opioids were more commonly prescribed in England, stronger opioids in Sweden. CONCLUSIONS: Temporal prevalence patterns of opioid prescribing between cases and controls are similar in England and Sweden. Opioids are still commonly used in TKR cases in both countries highlighting the lack of valid alternatives for OA pain management.

Are structural abnormalities on knee MRI associated with osteophyte development? Data from the Osteoarthritis Initiative.

OBJECTIVE: To assess which structural abnormalities on knee MRI are associated with development of osteophytes in middle-aged subjects without radiographic knee osteoarthritis. DESIGN: We included subjects from the Osteoarthritis Initiative, aged 40-55 years, Kellgren & Lawrence grade 0 in both knees, and knee MRIs from both knees available at baseline, 24, 48 and 72 months. Structural exposures on MRI assessed using MOAKS included cartilage damage, bone marrow lesions, meniscal tear, meniscal extrusion, and Hoffa/effusion synovitis. We assessed whether each structural exposure was associated with the development of osteophytes on MRI in the medial and lateral tibiofemoral, and patellofemoral compartment. We estimated hazard ratios (HR) including 95% confidence intervals (CI) for osteophyte development using a mixed complementary log-log regression model adjusted for age, sex, and body mass index. RESULTS: We included 680 knees from 340 subjects with a mean (SD) age of 50 years (3.0), and 51% men. In the medial tibiofemoral compartment, the absolute risk of osteophyte development in the first 24-month period was 4% in knees without, and 15% in knees with medial meniscal tear. Corresponding adjusted HR was 6.6 (95%CI = 3.4-12.9). In the lateral tibiofemoral compartment, the adjusted HR for developing osteophytes having a lateral meniscal tear was 3.3 (95%CI = 1.3-8.4). In the patellofemoral compartment, patellofemoral cartilage damage was most clearly associated with developing osteophytes (HR = 2.6, 95%CI = 1.8-3.7). CONCLUSIONS: Meniscal tear seem to be the strongest structural risk factor for the development of tibiofemoral osteophytes, and patellofemoral cartilage damage for the development of patellofemoral osteophytes, respectively. Local biomechanical factors are important in early osteophyte development.

The heritability of doctor-diagnosed traumatic and degenerative meniscus tears.

OBJECTIVE: To estimate the genetic contribution to traumatic and degenerative meniscus tears for men and women across the lifespan. METHODS: We linked the Swedish Twin Register with individual-level national healthcare data to form a 30-year, population-wide, longitudinal twin cohort. To study genetic contribution to meniscus tears, we estimated the heritability and familial risk using incident traumatic and degenerative tear diagnostic codes in a cohort of 88,414 monozygotic and dizygotic twin-pairs, aged ≥17 years. RESULTS: During follow-up, 3,372 (3.8%) of 88,414 twins were diagnosed with a traumatic or degenerative meniscus tear. The heritability was 0.39 (95% CI = 0.32-0.47) for men and 0.43 (95% CI = 0.36-0.50) for women, and did not vary by age. Environmental factors that were unique to each twin in a pair explained a greater proportion of the variance than genetic factors, both for men (0.61, 95% CI = 0.53-0.68) and women (0.57, 95% CI = 0.50-0.64). Separate analyses of traumatic vs degenerative meniscus tears yielded similar results. CONCLUSION: For the first time, we have estimated the genetic contribution to doctor-diagnosed meniscus tears using a twin study design. We found a relatively low to modest heritability for meniscus tears (∼40%). The heritability was also fairly stable over the lifespan, and equal in both men and women. Our findings suggest that environmental risk factors are a more important contributor to both traumatic and degenerative doctor-diagnosed meniscus tears than genetic factors.

Is meniscal status in the anterior cruciate ligament injured knee associated with change in bone surface area? An exploratory analysis of the KANON trial.

OBJECTIVES: To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area. DESIGN: We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI). RESULTS: We analyzed 109 subjects (median 27 (18-36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0-2.3%) and 1.4% (95%CI 0.6-2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3-2.0%) and 1.3% (95%CI 0.6-2.0%) for medial and lateral newly developed pathology, respectively. CONCLUSION: Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559.

Quantitative three-dimensional collagen orientation analysis of human meniscus posterior horn in health and osteoarthritis using micro-computed tomography.

OBJECTIVE: Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (µCT), and to compare the local microstructural organization between OA and donor samples. METHOD: We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with µCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel. RESULTS: In donor samples, meniscus bundles were aligned circumferentially around the inner border of meniscus. In medial OA menisci, the organized structure of collagen network was lost, and main orientation was shifted away from the circumferential alignment. Quantitatively, medial OA menisci had the lowest mean orientation angle compared to all groups, -24° (95%CI -31 to -18) vs medial donor and -25° (95%CI -34 to -15) vs lateral OA. CONCLUSIONS: HMDS-based µCT imaging enabled quantitative analysis of meniscal collagen fiber bundles and their orientations in 3D. In human medial OA menisci, the collagen disorganization was profound with overall lower orientation angles, suggesting collagenous microstructure disorganization as an important part of meniscus degradation.

Proteomic comparison of osteoarthritic and reference human menisci using data-independent acquisition mass spectrometry.

OBJECTIVE: Recent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry. DESIGN: Tissue plugs of Ø3 mm were obtained from the posterior horns of the lateral and medial menisci from one knee of 10 knee-healthy deceased donors and 10 patients undergoing knee replacement. Proteins were extracted and prepared for mass spectrometric analysis. Statistical analysis was conducted on abundance data that was log2-transformed, using a linear mixed effects model and evaluated using pathway analysis. RESULTS: We identified a total of 835 proteins in all samples, of which 331 were included in the statistical analysis. The largest differences could be seen between the medial menisci from OA patients and references, with most proteins showing higher intensities in the medial menisci from OA patients. Several matrix proteins, e.g., matrix metalloproteinase 3 (MMP3) (4.3 times higher values [95%CI 1.8, 10.6]), TIMP1 (3.5 [1.4, 8.5]), asporin (4.1 [1.7, 10.0]) and versican (4.4 [1.8, 10.9]), all showed higher abundance in medial menisci from OA patients compared to medial reference menisci. OA medial menisci also showed increased activation of several pathways involved in inflammation. CONCLUSION: An increase in protein abundance for proteins such as MMP and TIMP1 in the medial menisci from OA patients suggests simultaneous activation of both catabolic and anabolic processes that warrants further attention.

Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years.

OBJECTIVE: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. METHODS: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. RESULTS: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. CONCLUSION: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.

Inappropriate opioid dispensing in patients with knee and hip osteoarthritis: a population-based cohort study.

OBJECTIVE: To estimate inappropriate opioid dispensing in patients with knee or hip osteoarthritis (OA) defined as (1) dispensing of opioids within the first year of diagnosis or (2) long-term opioid use. DESIGN: Data from Skåne Healthcare Register was linked with the Swedish Prescribed Drug Register. Incidence proportion of dispensed opioids within first year of incident knee or hip OA diagnosis was determined in knee (n = 399,670) and hip (413,216) OA cohorts without a history of OA. The 1-year period prevalence of long-term opioid dispensing was determined in a prevalence cohort (n = 48,574 with knee and/or hip OA and n = 457,587 without OA). The proportion of OA patients with excess opioid dispensing attributable to OA was estimated using inverse probability weighted regression adjustment. RESULTS: In the incident cohorts, 5866 and 2359 developed knee and hip OA, respectively. Within the first year after OA diagnosis 14.7% patients with knee OA and 20.7% with hip OA had an opioid dispensed. The estimated inappropriate dispensing attributable to OA was 7.4% (95% CI 6.5-8.4) for knee OA and 12.8% (95% CI 11.1-14.4) for hip OA. Among persons with prevalent knee, hip or knee and hip OA inappropriate, long-term opioid use attributable to OA was 1.3%, 2.0% and 2.4% of, respectively. CONCLUSIONS: More than half the incident opioid dispensations to patients within their first year after knee or hip OA diagnosis are inappropriate according to current treatment guidelines. Furthermore, 2% of patients with prevalent knee or hip OA have inappropriate long-term dispensing of opioids.

Three-dimensional microstructure of human meniscus posterior horn in health and osteoarthritis.

OBJECTIVE: To develop and perform ex vivo 3D imaging of meniscus posterior horn microstructure using micro-computed tomography (µCT), and to compare specimens from healthy references against end-stage osteoarthritis (OA) using conventional section-based histology and qualitative µCT. DESIGN: We retrieved human medial and lateral menisci from 10 deceased donors without knee OA (healthy references) and medial and lateral menisci from 10 patients having total knee replacement for medial compartment OA. Meniscal posterior horns were dissected and fixed in formalin. One subsection underwent hexamethyldisilazane (HMDS) treatment and µCT imaging. Pauli's histopathological scoring was performed for 3 other subsections. The differences in histopathological scores were estimated using mixed linear regression, resulting in fixed effects estimates for within-knee comparisons and adjusted for age and body mass index for between-subjects comparisons. RESULTS: 3D visualization with µCT qualitatively revealed similar microstructural changes in the posterior horns as conventional histology. The mean histopathological score was higher for medial menisci from OA knees vs both medial reference menisci (mean difference [95% CI], 3.9 [2.6,5.3]), and lateral menisci from OA knees (3.9 [2.9,5.0]). The scores were similar between lateral menisci from OA knees and lateral reference menisci (0.8 [-0.6,2.2]), and between medial and lateral reference menisci (0.8 [-0.3,1.9]). CONCLUSIONS: HMDS-based µCT protocol allows unique 3D visualization of meniscus microstructures. Posterior horns of medial menisci from medial compartment OA knees had higher histopathological scores than both the lateral posterior horns from the same OA knees and medial reference menisci, suggesting a strong association between meniscus degradation and unicompartmental knee OA.

Cause-specific mortality in osteoarthritis of peripheral joints.

PURPOSE: To estimate cause-specific mortality in osteoarthritis patients compared to the general population. METHODS: We identified all residents in southern Sweden aged 45-84 years in 2003. Through the Skåne Healthcare Register (SHR) we identified those diagnosed with osteoarthritis in peripheral joints between 1998 and 2003. We followed all residents from 2004 until relocation outside of the region, death, or end of 2014. We classified the underlying cause of death from death certificates into: cardiovascular and neoplasms, diabetes, infections, dementia, diseases of digestive system, or other causes. For estimation, we used multi-state adjusted Cox proportional hazards models. RESULTS: We identified 15,901 patients (mean age [SD] 67 years [10], 41% men) with prevalent doctor-diagnosed osteoarthritis in knee, 9347 in hip, 4004 in hand and 5447 in other peripheral joints among 469,177 residents. For most causes of death in osteoarthritis patients, we found no increased mortality, with hazard ratios (HRs) close to 1, similar for men and women. However, for knee and hip osteoarthritis and cardiovascular death, HRs were non proportional and increased to 1.19 (95%CI 1.10, 1.28) and 1.13 (1.03, 1.24) during 9-11 years of follow-up, mostly due to excess mortality from chronic ischemic heart diseases and heart failure. CONCLUSIONS: The risk of cardiovascular excess deaths increases with duration of knee and hip osteoarthritis. The major contributors are chronic ischemic heart diseases and heart failure. Our results call for improved implementation of osteoarthritis treatment guidelines, with major focus on interventions to address mobility limitations and maintaining or increase physical activity level.

Opioid use in knee or hip osteoarthritis: a region-wide population-based cohort study.

OBJECTIVE: To quantify opioid use in knee and hip osteoarthritis (OA) patients, and to estimate the proportion of opioids in the population attributable to OA patients. DESIGN: Population-based cohort study. METHODS: We included 751,579 residents in southern Sweden, aged ≥35 years in 2015. Doctor-diagnosed knee or hip OA between 1998 and 2015 was the exposure. Dispensed weak and strong opioids were identified between November 2013 and October 2015 from the Swedish Prescribed Drug Register (SPDR). We determined age- and sex-standardized 12-month period prevalence of opioid use from November 2014 until October 2015 and calculated prevalence ratios and incidence rate ratios adjusted for age, sex, and other socio-demographic variables. We estimated the population attributable fraction (PAF) of incident opioid use attributable to OA patients. RESULTS: The 12-month prevalence of opioid use among OA patients was 23.7% [95% confidence intervals (CI) 23.3-24.2], which was two-fold higher compared to individuals without knee or hip OA: prevalence ratio: 2.1 [95% CI 2.1-2.1]. Similarly, OA patients were more likely to have an incident opioid dispensation, especially for strong opioids (incidence rate ratio: 2.6 [95% CI 2.5-2.7]). Population attributable tractions (PAF) of incident opioid use attributable to OA patients was 12%, 9% for weak and 17% for strong opioids. CONCLUSIONS: Every fourth patient with knee or hip OA has opioids dispensed over a 1-year period, and 12% of incident opioid dispensations are attributable to OA and/or its related comorbidities. These results highlight that patients with knee and hip OA constitute a group of patients with an alarmingly high use of opioids.

Scrutinizing the cut-off for "pathological" meniscal body extrusion on knee MRI.

OBJECTIVES: Medial meniscal body extrusion ≥ 3 mm on MRI is often considered "pathologic." The aims of this study were to (1) assess the adequacy of 3 mm as cut-off for "pathological" extrusion and (2) find an optimal cut-off for meniscal extrusion cross-sectionally associated with radiographic knee osteoarthritis, bone marrow lesions (BMLs), and cartilage damage. METHODS: Nine hundred fifty-eight persons, aged 50-90 years from Framingham, MA, USA, had readable 1.5 T MRI scans of the right knee for meniscal body extrusion (measured in mm). BMLs and cartilage damage were read using the whole organ magnetic resonance imaging score (WORMS). Knee X-rays were read according to the Kellgren and Lawrence (KL) scale. We evaluated the performance of the 3-mm cut-off with respect to the three outcomes and estimated a new cut-off maximizing the sum of sensitivity and specificity. RESULTS: The study persons had mean age of 62.2 years, 57.0% were women and the mean body mass index was 28.5 kg/m2. Knees with radiographic osteoarthritis, BMLs, and cartilage damage had overall more meniscal extrusion than knees without. The 3-mm cut-off had moderate sensitivity and low specificity for all three outcomes (sensitivity between 0.68 [95% CI 0.63-0.73] and 0.81 [0.73-0.87], specificity between 0.49 [0.45-0.52] and 0.54 [0.49-0.58]). Using 4 mm maximized the sum of sensitivity and specificity and improved the percentage of correctly classified subjects (from between 54 and 61% to between 64 and 79%). CONCLUSIONS: The 4-mm cut-off may be used as an alternative cut-off for denoting pathological meniscal extrusion. KEY POINTS: • Medial meniscal body extrusion is strongly associated with osteoarthritis. • The 3-mm cut-off for medial meniscal body extrusion has high sensitivity but low specificity with respect to bone marrow lesions, cartilage damage, and radiographic osteoarthritis. • The 4-mm cut-off maximizes the sensitivity and specificity with respect to all three osteoarthritis features.

Nature vs nurture in knee osteoarthritis - the importance of age, sex and body mass index.

OBJECTIVE: (1) To estimate the life-time genetic contribution for knee osteoarthritis (OA) surgery and (2) to explore any differences in the genetic contribution across age, sex and body mass index (BMI). METHODS: We studied the sex-specific genetic contribution to knee OA surgery in a prospective cohort study of 62,490 twins aged 35 years or older with a follow-up period of up to 47 years (10,092 identical and 21,153 non-identical twin pairs, 54% women). To study interactions with age, we graphed the heritabilities over the lifespan for men and women. We also studied the sex-specific heritability across strata of the median BMI to explore any interactions with BMI. RESULTS: The overall heritability of knee OA surgery was 0.53 (95% confidence intervals [CI] = 0.31-0.75), with higher heritability among women (H2 = 0.80 (95% CI = 0.73-0.87)) than men (H2 = 0.39 (95% CI = 0.10-0.69)). For men, the heritability started to rise after age 68. The genetic contribution was particularly low in men above median BMI (H2≥23.7 kg/m2 = 0.08, 95% CI = -0.32-0.48). For women, the heritability was consistently high from age 50 to death, independently of BMI (H2≥22.5 kg/m2 = 0.77, 95% CI = 0.66-0.87). CONCLUSION: There is a higher and more consistent genetic contribution for knee OA surgery in women than men. In men the genetic contribution was relatively low and varied with age and BMI.

A naturally aging knee, or development of early knee osteoarthritis?

AIM: To study the development of early knee osteoarthritis (OA) in subjects with and without risk factors for knee OA. METHODS: We studied 340 subjects from the Osteoarthritis Initiative (OAI), aged 45-55 years (51% women), free of radiographic knee OA at baseline (n = 294 with and n = 46 without knee pain and other OA risk factors). At baseline, 24, 48, 72 and 96 months we compared the two groups for prevalence and overlap of knee OA as defined by magnetic resonance imaging (MRI-based OA), x-rays (Kellgren-Lawrence grade [KLG] ≥ 1), and pain, using a logistic mixed model. We studied the group differences (%) over time by subtracting the OA prevalence of those without risk factors from the group with risk factors. RESULTS: The group with OA risk factors had higher proportions of MRI-based OA than the group without OA risk factors at all visits, but the difference diminished at 72 months (72 months difference = 11.9%, 95% confidence intervals [CI] = -2.3-26.1). Further, at 72 months, the presence of KLG ≥ 1 were similar in the two groups (-3.5%, 95% CI = -15.2-8.2). The proportion fulfilling all three OA definitions was 1.7% at 24 months and 4.8% at 72 months of those with OA risk factors and 0% and 2.2%, respectively, in those without. CONCLUSION: Structural changes of the knee are common irrespective of the presence of pain or other OA risk factors. Such structural changes in absence of knee symptoms should probably be considered as risk factors for early OA rather than disease.

Change in patient-reported outcomes in patients with and without mechanical symptoms undergoing arthroscopic meniscal surgery: A prospective cohort study.

OBJECTIVE: Patients with degenerative or traumatic meniscal tears are at high risk of developing knee osteoarthritis. We investigated if younger (≤40 years) and older (>40 years) patients with preoperative mechanical symptoms (MS) improved more in patient-reported outcomes after meniscal surgery than those without MS. DESIGN: Patients from Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing arthroscopic surgery for a meniscal tear completed online questionnaires before surgery, and at 12 and 52 weeks follow-up. Questionnaires included self-reported presence of MS (i.e., sensation of catching and/or locking) and the Knee injury and Osteoarthritis Outcome Score (KOOS). We analyzed between-group differences in change in KOOS4 from baseline to 52 weeks, using an adjusted mixed linear model. RESULTS: 150 younger patients (mean age 31 (SD 7), 67% men) and 491 older patients (mean age 54 (SD 9), 53% men) constituted the baseline cohorts. Patients with MS generally had worse self-reported outcomes before surgery. At 52 weeks follow-up, younger patients with preoperative MS had improved more in KOOS4 scores than younger patients without preoperative MS (adjusted mean difference 10.5, 95% CI: 4.3, 16.6), but did not exceed the absolute postoperative KOOS4 scores observed for those without MS. No difference in improvement was observed between older patients with or without MS (adjusted mean difference 0.7, 95% CI: -2.6, 3.9). CONCLUSIONS: Younger patients (≤40 years) with preoperative MS experienced greater improvements after arthroscopic surgery compared to younger patients without MS. Our observational study result needs to be confirmed in randomized trials.