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Osteoarthritis (OA) remains the most challenging arthritic disorder, with a high burden of disease and no available disease-modifying treatments. Symptomatic early-stage OA of the knee (the focus of this Review) urgently needs to be identified and defined, as efficient early-stage case finding and diagnosis in primary care would enable health-care providers to proactively and substantially reduce the burden of disease through proper management including structured education, exercise and weight management (when needed) and addressing lifestyle-related risk factors for disease progression. Efforts to define patient populations with symptomatic early-stage knee OA on the basis of validated classification criteria are ongoing. Such criteria, as well as the identification of molecular and imaging biomarkers of disease risk and/or progression, would enable well-designed clinical studies, facilitate interventional trials, and aid the discovery and validation of cellular and molecular targets for novel therapies. Treatment strategies, relevant outcomes and ethical issues also need to be considered in the context of the cost-effective management of symptomatic early-stage knee OA. To move forwards, a multidisciplinary and sustained international effort involving all major stakeholders is required.In this Review, the authors assess the current understanding of symptomatic early-stage knee osteoarthritis, including its diagnosis and classification, and highlight important gaps in knowledge that will need to be addressed to enable effective management.

Osteoarthritis is one of the most common musculoskeletal diseases and increases the risk of severe cardiovascular disease, like heart attack and stroke. In some individuals, osteoarthritis and cardiovascular disease will co-occur. This co-occurrence might be due to shared risk factors, for example high age, lifestyle factors and/or a shared genetic liability for the two diseases. Here, we show that the correlation between osteoarthritis and cardiovascular disease can be explained by shared genetic factors, independent of high age and body weight, and also likely independent of lifestyle factors, like smoking and physical activity level. Findings suggest that genetic factors that are shared for osteoarthritis and cardiovascular disease may contribute to both diseases. Thus, the prevailing idea that osteoarthritis is predominantly a risk factor for cardiovascular disease is challenged. Our findings imply that the current diagnostic boundaries between these diseases may need to be re-evaluated. Osteoarthritis is considered a risk factor for severe cardiovascular disease like ischemic heart disease and myocardial infarction. Studying ~60 000 twins over a 20-year period and applying bivariate classical twin models, this manuscript suggests that shared genetic factors for osteoarthritis and cardiovascular disease may contribute to both diseases.

ObjectivesWe aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture.MethodsWe used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture.ResultsThe incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture.ConclusionThe genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.

The SARS-CoV-2 Omicron (B.1.1.529) variant has been associated with less severe acute disease, however, concerns remain as to whether long-term complaints persist to a similar extent as for earlier variants. Studying 1 323 145 persons aged 18-70 years living in Norway with and without SARS-CoV-2 infection in a prospective cohort study, we found that individuals infected with Omicron had a similar risk of post-covid complaints (fatigue, cough, heart palpitations, shortness of breath and anxiety/depression) as individuals infected with Delta (B.1.617.2), from 14 to up to 126 days after testing positive, both in the acute (14 to 29 days), sub-acute (30 to 89 days) and chronic post-covid (≥90 days) phases. However, at ≥90 days after testing positive, individuals infected with Omicron had a lower risk of having any complaint (43 (95%CI = 14 to 72) fewer per 10,000), as well as a lower risk of musculoskeletal pain (23 (95%CI = 2-43) fewer per 10,000) than individuals infected with Delta. Our findings suggest that the acute and sub-acute burden of post-covid complaints on health services is similar for Omicron and Delta. The chronic burden may be lower for Omicron vs Delta when considering musculoskeletal pain, but not when considering other typical post-covid complaints. The SARS-CoV-2 Omicron variant is associated with less severe disease but less is known about variant-specific risk of long-term complaints. Monitoring 1.3 million individuals from Norway for post-acute COVID-19 complaints up to 126 days shows that the burden is similar for Omicron and Delta for most complaints except for musculoskeletal pain.

Background Obesity and type 2 diabetes (T2DM) are considered risk factors for complications following total hip arthroplasty (THA). How these risk factors separately or in combination influence the risk of reoperation due to periprosthetic joint infection (PJI) or all-cause reoperation is not fully known. We sought to investigate the 2-year risk of reoperation following THA due to osteoarthritis (OA) among people with and without the metabolic risk factors, T2DM and obesity. Methods We linked all patients with THA registered during 2008–2019 in the Swedish Hip Arthroplasty Register (SHAR) to the National Diabetes Register. The risk of reoperation was analysed by applying Kaplan–Meier (KM) and multivariable Cox regression analyses. Subgroup analyses were performed to explore the effect modification by obesity. After THA exclusions (such as bilateral THA observations and other diagnoses than OA) there were 14,512 individuals identified with T2DM and 116,579 without. The primary outcome was reoperation due to PJI within two years after THA. The secondary outcome was reoperation due to any cause within two years after THA. Results 2-year 1–KM reoperation estimate for reoperation due to PJI was 1.69% with 95% confidence interval (95%CI) 1.47–1.90 among individuals with T2DM and 1.02% (95%CI 0.96–1.08) among those without T2DM. The 1–KM reoperation estimate for reoperation due to any cause was 2.67% (95%CI 2.40–2.94) for the T2DM group, and 1.99% (95%CI 1.91–2.07) for non-T2DM. However, adjusted for Body Mass Index (BMI), T2DM was not a statistically significant risk factor (infection-related reoperation: adjusted hazard ratio (aHR) 1.1 with 95% confidence interval (95%CI) 0.9–1.3; all-cause reoperation: aHR 1.0, 95%CI 0.9–1.2). In the BMI subgroup analyses, T2DM associated increased risk of reoperation due to PJI was limited to normal/underweight individuals (aHR 1.6 95%CI 1.1–2.4). In the subgroups with overweight or obesity, T2DM was neither associated with increased risk of all-cause reoperation nor reoperation due to PJI. Conclusions Overall, T2DM is not an independent risk factor for reoperation when adjusted for BMI. However, T2DM constitutes a minor risk factor in individuals of normal/underweight. Risk of reoperation was more strongly associated with BMI rather than T2DM, suggesting that the additional risk observed in obese patients is likely influenced by multiple interrelated factors beyond T2DM alone.

Background Knee arthroscopy is one of the most common surgical procedures worldwide and the number of arthroscopies has substantially increased in the last 30 years. Thus, our aim was to provide updated estimates on the risk of complications and compare it with the background risk in the general population. Methods We identified patients aged 15–84 years with knee arthroscopy in the years 2005–2016 in southern Sweden. We calculated the risk of pyogenic arthritis, venous thromboembolism, and other typical complications within 30 days. As a reference cohort we included the regional population in the corresponding age interval. We estimated the relative and absolute risks of complications compared to the reference cohort using logistic regression adjusted for age, sex, and level of education. We also estimated the proportion of complications in the population explained by knee arthroscopy (population attributable fraction). Results We identified 18,735 knee arthroscopy patients (mean age 39 years) and 1,171,084 reference subjects (mean age 46 years). The absolute risk of one or more complications was 1.1% after knee arthroscopy and 0.16% in references. The odds ratio of any complication after knee arthroscopy vs. the reference cohort was 9.4 (95% confidence interval [CI] 8.1, 10.9) with an absolute risk difference of 1.4% (1.1, 1.6%). The relative risk (95% CI) for pyogenic arthritis was 115 (75, 174), venous thromboembolism 6.8 (5.1, 9.1), and other complications 7.7 (6.3, 9.5). The population attributable fraction for pyogenic arthritis was 5%. Conclusions The absolute risks of complications associated with knee arthroscopy remain small at about 1%. Still, 5% of all pyogenic knee arthritis cases in adults are attributable to knee arthroscopy, thus risks with knee arthroscopy should be carefully considered in the choice of treatment.

Loss of meniscal function is one of the strongest identified risk factors for knee osteoarthritis (OA). However, the best therapeutic strategy for patients with meniscus damage remains controversial. The authors explain the role of meniscus pathology in OA and discuss the current options for treatment of degenerative and traumatic meniscal tears. The menisci are internal structures that are of central importance for a healthy knee joint; they have a key role in the structural progression of knee osteoarthritis (OA), and the risk of the disease dramatically increases if they are damaged by injury or degenerative processes. Meniscus damage might be considered a signifying feature of incipient OA in middle-aged and elderly people. As approximately every third knee of people in these groups has a damaged meniscus, tears are common incidental findings of knee MRI. However, as most tears do not cause symptoms, careful clinical evaluation is required to determine if a damaged meniscus is likely to directly impact a patient's symptoms. Conservative management of patients with knee pain and a degenerative meniscal tear should be considered as a first-line therapy before surgical treatment is contemplated. Patients with mechanical interference of joint movements, such as painful catching or locking, might need surgical treatment with meniscal repair if possible. In a subset of patients, meniscal resection might relieve pain and other symptoms that potentially originate directly from the torn meniscus. However, the possibility of an increased risk of OA if functional meniscal tissue is removed cannot be overlooked. Key Points Meniscus damage is highly prevalent in middle-aged and elderly people in the general population Most meniscal tears do not cause knee pain Meniscus damage is almost always present in knees with radiographic osteoarthritis (OA) Meniscus damage might lead to OA and OA might lead to meniscus damage Conservative management (patient education, weight reduction and/or physical exercise therapy), should always be the first treatment of choice for patients with knee pain and degenerative meniscus damage Patients who experience painful catching or locking of their knee due to an unstable meniscal tear might require surgical treatment

We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18–70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5–6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6–13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.

ObjectivesTo assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up.DesignMulticentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial.SettingOrthopaedic departments in five public hospitals in Finland.Participants146 adults, mean age 52 years (range 35–65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised.InterventionsAPM or placebo surgery (diagnostic knee arthroscopy).Main outcome measuresWe used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ≥1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale).ResultsThere was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ≥1 of 13%, 95% CI −2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), −1.7 (95% CI −7.7 to 4.3) in WOMET, −2.1 (95% CI −6.8 to 2.6) in Lysholm knee score, and −0.04 (95% CI −0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar.ConclusionsAPM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery.Trial registrationClinicalTrials.gov (NCT01052233 and NCT00549172).

Cardiovascular, respiratory, and musculoskeletal disease are among the leading causes of disability in middle-aged and older people. Health and lifestyle factors in youth have known associations with cardiovascular or respiratory disease in adulthood, but largely unknown associations with musculoskeletal disease. We included approximately 40,000 18-year-old Swedish males, who completed their conscription examination in 1969 to 1970, followed up until age of 60 years. Exposures of interest were physical health: body mass and height, blood pressure, pulse at rest, muscle strength, cardiorespiratory fitness, and hematocrit; self-reported lifestyle: smoking, alcohol, and drug use; self-reported health: overall, headache and gastrointestinal. We followed the participants through the Swedish National Patient Register for incidence of common musculoskeletal (osteoarthritis, back pain, shoulder lesions, joint pain, myalgia), cardiovascular (ischemic heart disease, atrial fibrillation), and respiratory diseases (asthma, chronic obstructive pulmonary disease, bronchitis). We analyzed the associations using general estimating equations Poisson regression with all exposures included in one model and adjusted for parental education and occupation. We found that higher body mass was associated with higher risk of musculoskeletal (risk ratio [RR] per 1 standard deviation [SD] 1.12 [95% confidence interval, CI 1.09, 1.16]), cardiovascular (RR 1.22 [95% CI 1.17, 1.27] per 1 SD) and respiratory diseases (RR 1.14 [95% CI 1.05, 1.23] per 1 SD). Notably, higher muscle strength and cardiorespiratory fitness were associated with higher risk of musculoskeletal disease (RRs 1.08 [95% CI 1.05, 1.11] and 1.06 [95% CI 1.01, 1.12] per 1 SD difference in exposure), while higher cardiorespiratory fitness was protective against both cardiovascular and respiratory diseases (RRs 0.91 [95% CI 0.85, 0.98] and 0.85 [95% CI 0.73, 0.97] per 1 SD exposure, respectively). We confirmed the adverse effects of smoking, with risk ratios when comparing 11+ cigarettes per day to non-smoking of 1.14 (95% CI 1.06, 1.22) for musculoskeletal, 1.58 (95% CI 1.44, 1.74) for cardiovascular, and 1.93 (95% CI 1.60, 2.32) for respiratory diseases. Self-reported headache (category \"often\" compared to \"never\") was associated with musculoskeletal diseases (RR 1.38 [95% CI 1.21, 1.58]) and cardiovascular diseases (RR 1.29 [95% CI 1.07, 1.56]), but had an inconclusive association with respiratory diseases (RR 1.13 [95% CI 0.79, 1.60]). No large consistent associations were found for other exposures. The most notable associations with specific musculoskeletal conditions were for cardiorespiratory fitness and osteoarthritis (RR 1.23 [95% CI 1.15, 1.32] per 1 SD) and for muscle strength and back pain (RR 1.18 [95% CI 1.12, 1.24] per 1 SD) or shoulder diseases (RR 1.27 [95% CI 1.19, 1.36] per 1 SD). The main limitations include lack of adjustment for genetic factors and environmental exposures from childhood, and that the register data were available for males only. While high body mass was a risk factor for all 3 studied groups of diseases, high cardiorespiratory fitness and high muscle strength in youth were associated with increased risk of musculoskeletal disease in middle age. We speculate that these associations are mediated by chronic overload or acute trauma.