An open-label, single-arm trial of cryoneurolysis for improvements in pain, activities of daily living and quality of life in patients with symptomatic ankle osteoarthritis.

Objective: Cryoneurolysis, cold-induced reversible conduction block of peripheral nerves, is an effective treatment for reducing knee osteoarthritis (OA) symptoms and opioid use following knee arthroplasty. There are however, limited data concerning its use for ankle OA. Our aim was to assess clinically significant long-term symptomatic relief of ankle OA with cryoneurolysis. Method: This single-center, open-label trial included participants aged >18 years with radiographic tibiotalar OA, unilateral ankle pain ≥5/10 on Numerical Rating Scale (NRS), and with no ankle surgery within 6-months of screening. Following ultrasound-guided cryoneurolysis of nerves in the participant's pain distribution (sural, saphenous, superficial and/or deep fibular nerves), outcomes were assessed at clinic visits (6, 12 and 24-weeks) and by telephone interview (3, 9, 18-weeks). The primary endpoint was change in Foot and Ankle Outcome Score (FAOS) (pain subscale) at 12-weeks. Change in quality of life (FAOS-QoL), activities of daily living (FAOS-ADL), NRS-pain, and physical performance measures were also assessed. Longitudinal mixed models were constructed to evaluate changes from baseline at 6, 12- and 24-weeks post-treatment. Results: Forty participants enrolled (50% female, mean â€‹± â€‹SD age 63.0 â€‹± â€‹12.8 years). At 12-weeks post treatment, FAOS-pain (20.8, p â€‹< â€‹0.0001), ADL (18.1, p â€‹= â€‹0.0003), QoL (19.9, p â€‹= â€‹0.0003) and NRS-pain (-2.6, p â€‹< â€‹0.0001) were significantly improved from baseline. No difference in 40-m fast-paced walking test was detected at 12-weeks post-treatment (-1.2sec, p â€‹= â€‹0.59). For all outcomes, similar findings were observed at 6- and 24-week visits. Conclusion: Cryoneurolysis resulted in statistically significant improvements in ankle pain, physical function and QoL for up to 24-weeks in participants with unilateral, symptomatic ankle OA.

Survival of primary ankle replacements: data from global joint registries.

BACKGROUND: Ankle arthroplasty, commonly known as ankle replacement, is a surgical procedure for treating end-stage ankle osteoarthritis. Whilst evidence shows good clinical results after surgery, little is known of the long-term survival of ankle replacements and the need for ankle revision. Using more recent implant data and long-term data, there is now opportunity to examine at a population-level the survival rate for ankle implants, to examine between-country differences in ankle revision surgery, and to compare temporal trends in revision rates between countries. METHODS: Four national joint registries from Australia, New Zealand, Norway and Sweden provided the necessary data on revision outcome following primary ankle replacement, for various periods of observation - the earliest starting in 1993 up to the end of 2019. Data were either acquired from published, online annual reports or were provided from direct contact with the joint registries. The key information extracted were Kaplan-Meier estimates to plot survival probability curves following primary ankle replacement. RESULTS: The survival rates varied between countries. At 2 years, across all registries, survival rates all exceeded 0.9 (range 0.91 to 0.97). The variation widened at 5 years (range 0.80 to 0.91), at 10 years (range 0.66 to 0.84) and further at 15-years follow-up (0.56 to 0.78). At each time point, implant survival was greater in Australia and New Zealand with lower rates in Sweden and Norway. CONCLUSIONS: We observed variation in primary ankle replacement survival rates across these national registries, although even after 5 years, these population derived data show an 80% revision free survival. These data raise a number of hypotheses concerning the reasons for between-country differences in revision-free survival which will require access to primary data for analysis.

Magnetic Resonance Imaging-Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. METHODS: We used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. RESULTS: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. CONCLUSION: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.

Effect of Heeled Shoes on Joint Symptoms and Knee Osteoarthritis in Older Adults: A 5-Year Follow-Up Study.

OBJECTIVE: Our aims were to examine the effects of heeled shoes on incident knee osteoarthritis (OA) and joint pain. METHODS: We used longitudinal data from the Chingford 1000 Women Study (Chingford Study), a prospective cohort of women aged 50 years or older. Participants with musculoskeletal disorders and/or a history of knee-related injury/surgery were excluded. Participants were followed for up to 5 years for incident outcomes including 1) radiographic knee OA (RKOA) and 2) joint pain (feet, knees, hips, and back). Footwear data, including ever worn heels of 2 inches or more and daytime/evening hours (per week) spent wearing heeled shoes over five decades (ages <20 years, 20-30 years, 30-40 years, and >50 years), were available at Year 10 whereas knee radiographs and joint symptom data were also collected at Year 15. Cumulative time spent wearing heeled shoes was calculated for women reporting ever-use of heeled shoes (≥2 inches). Multiple logistic regression was used to examine the relationship between exposures and outcomes (from Year 10 to Year 15). RESULTS: A total of 356 women were eligible at Year 10 with a median (interquartile range) age of 60 (56-65) years. Compared with non-use, ever-use of heeled shoes (≥2 inches) was not associated with incident RKOA (1.35; 95% confidence interval: 0.56-3.27). No associations were observed between increasing cumulative time spent wearing heels and incident outcomes. CONCLUSION: Compared with the non-use of heeled shoes, ever-use of heels (≥2 inches) was not associated with incident RKOA and incident joint symptoms. Further, increasing cumulative time spent wearing heels was not associated with any of our outcomes.

Monitoring work-related physical activity and estimating lower-limb loading: a proof-of-concept study.

BACKGROUND: Physical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants. METHODS: Twenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone. RESULTS: Participants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3). CONCLUSIONS: There are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA.

Trends in the Utilization of Ankle Replacements: Data From Worldwide National Joint Registries.

BACKGROUND: Over the past decade, there has been a growth in the use of ankle replacements. Data from national joint registries have shown between-country differences in the utilization of ankle replacement. The reasons for these differences are, however, not well understood. Our aims were to describe and compare the annual incidence of primary ankle replacement between countries and, to examine potential reasons for variation over time. METHODS: We used aggregate data and summary statistics on ankle replacements for the period 1993 to 2019 from national joint replacement registries in Australia, Finland, New Zealand, Norway, Sweden and the United Kingdom. From the annual recorded counts of procedures, demographic data were extracted on age, sex distribution, and indication(s) for primary ankle replacement. Registry-level summary results were also obtained on data completeness, counts of hospitals/units, and health care providers performing ankle replacements annually and data collection processes (mandatory vs voluntary). Annual ankle replacement incidence for all diagnoses and, by indication categories (osteoarthritis [OA] and rheumatoid arthritis [RA]), were calculated per 100 000 residential population aged ≥18 years. RESULTS: For the period with data from all 6 countries (2010-2015), New Zealand had the largest annual incidence (mean ± SD) of 3.3 ± 0.2 ankle replacement procedures per 100 000 population whereas Finland had the lowest incidence (0.92 replacements). There were no common temporal trends in the utilization of ankle replacements. Over the years studied, OA was the predominant diagnosis in the United Kingdom, Australia, and New Zealand, whereas RA was the most common indication in Scandinavia. CONCLUSION: In these 6 countries, we found marked differences in the utilization of ankle replacements. Registry-related factors including data completeness and the number of hospitals/surgeons performing ankle replacements are likely to contribute to the observed between-country differences and need to be carefully considered when interpreting comparisons for this less common site for joint replacement surgery. LEVEL OF EVIDENCE: Level III, retrospective study.

Association between current medication use and progression of radiographic knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. METHODS: We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren-Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. RESULTS: Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = -0.042, 95% CI -0.08, -0.0004). No other associations were observed. CONCLUSIONS: In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

Foot and ankle pain and risk of incident knee osteoarthritis and knee pain: Data from the Multicentre Osteoarthritis Study.

OBJECTIVES: To examine whether foot and/or ankle pain increases the risk of knee OA. DESIGN: We utilised longitudinal data from the Multicentre Osteoarthritis Study (MOST); a community-based cohort of risk factors for knee OA. Participants without frequent knee pain (clinic visit only) and radiographic knee OA (RKOA) at baseline and, with no evidence of inflammatory musculoskeletal disease and a history of knee-related surgery were followed for up to 84-months for incident outcomes; i) RKOA (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent pain in the same knee) and iii) frequent knee pain only. At baseline, ankle and foot symptoms were assessed, with knee radiographs and symptoms also assessed at 30, 60 and 84-months. Our exposures included baseline ankle, foot, and ankle and foot pain (participant-level). Associations between foot and/or ankle pain and incident outcomes were assessed using multiple logistic regression, with adjustment for participant characteristics and ankle/foot pain. RESULTS: No statistically significant associations were observed between ankle, foot and, ankle and foot pain and incident RKOA, respectively. Ankle pain with (2.30, 95% CI 1.13 to 4.66) and without foot pain (OR: 2.53, 95% CI 1.34 to 4.80) were associated with increased odds of incident symptomatic RKOA and frequent knee pain. No statistically significant associations were observed between foot pain and these outcomes. CONCLUSIONS: Ankle pain should be a focus point, more so than foot pain, in the management of knee OA. Future studies should include additional ankle joint-specific symptom questions to better elucidate the knee OA biomechanical pathway.

Occupation and risk of knee osteoarthritis and knee replacement: A longitudinal, multiple-cohort study.

OBJECTIVES: To examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults. METHODS: We used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations). RESULTS: Heavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression. CONCLUSION: Heavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

BACKGROUND: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA. METHODS: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N = 50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling. RESULTS: The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3 years (SD 6.5) and 74% were female. There was no significant difference at 2 years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (- 313.5 mm3, 95% CI -4244.7 to 3617.7). CONCLUSIONS: Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA. TRIAL REGISTRATION: VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/.