Association of Calcaneal Bone Marrow Lesions and Plantar Fascia Imaging Biomarkers With Chronic Plantar Heel Pain: A Case-Control Study.

OBJECTIVE: To determine associations between chronic plantar heel pain (CPHP) and imaging biomarkers derived from magnetic resonance imaging (MRI) and ultrasonography. METHODS: We compared 218 participants with CPHP with 100 age- and sex-matched population controls. We assessed imaging biomarkers on MRI (calcaneal bone marrow lesions [BMLs], plantar fascia [PF] signal and thickness, spurs, and fat pad signal) and B-mode/power Doppler ultrasound (PF thickness, echogenicity, and vascularity). Covariate data collected included demographic characteristics, disease history, clinical measures, and physical activity by accelerometry. Data were analyzed using multivariable conditional logistic regression. RESULTS: Plantar calcaneal BML size (mm2 , odds ratio [OR] 1.03 [95% confidence interval (95% CI) 1.02-1.05]), larger plantar spurs (OR for spurs >5 mm 2.15 [95% CI 1.13-4.10]), PF signal (OR for signal penetrating >50% of the dorsoplantar width 12.12 [95% CI 5.36-27.42]), PF thickness (mm, OR for MRI 3.23 [95% CI 2.36-4.43] and ultrasound OR 3.78 [95% CI 2.69-5.32]), and echogenicity (diffusely hypoechoic OR 7.89 [95% CI 4.02-15.48] and focally hypoechoic OR 24.92 [95% CI 9.60-64.69]) were independently associated with CPHP. PF vascularity was uncommon, occurring exclusively in cases (cases with signal n = 47 [22%]). Combining imaging biomarkers into 1 model, plantar BMLs and PF imaging biomarkers, but not fat pad signal or heel spurs, were independently associated with CPHP. CONCLUSION: Calcaneal BMLs and PF imaging biomarkers are associated with CPHP. Further research is required to understand whether these different markers represent distinct phenotypes of heel pain, and if so, whether there are specific treatment implications.

Prevalence and Clinical Significance of Residual or Reconverted Red Bone Marrow on Knee MRI.

BACKGROUND: Residual/reconverted red bone marrow (RBM) in adult knees is occasionally observed on routine knee magnetic resonance imaging (MRI). We aimed to identify its prevalence, distribution, and associations with lifestyle factors, knee structural abnormalities, and knee symptoms in young adults. METHODS: Participants (n = 327; aged = 31-41 years) were selected from the Childhood Determinants of Adult Health (CDAH) knee study. They underwent T1-weighted and proton-density-weighted fat-suppressed MRI scans of knees. Residual/reconverted RBM in distal femur and proximal tibia were graded semi-quantitatively (grades: 0-3) based on the percentage area occupied. Knee structural abnormalities were graded semi-quantitatively using previously published MRI scoring systems. Knee symptoms (pain, stiffness, and dysfunction) were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale during CDAH knee study (year: 2008-2010) and at 6-9-year follow-up during the CDAH-3 study (year: 2014-2019). Associations between definite RBM (grade ≥ 2) and lifestyle factors, knee symptoms, and structural abnormalities were described using log-binomial regressions. RESULTS: Definite RBM was seen in females only, in 29 out of 154 cases (18.8%), with femoral involvement preceding tibial involvement. Definite RBM was associated with increased BMI (PR = 1.09/kg/m2; 95% CI: 1.03, 1.16), overweight status (PR = 2.19; 95% CI: 1.07, 4.51), and WOMAC knee pain (PR = 1.75; 95% CI: 1.11, 2.74) in cross-section analysis. However, there was no association between RBM and knee-pain after seven years (PR = 1.15; 95% CI: 0.66, 2.00). There were no associations between RBM and knee structural abnormalities. CONCLUSION: Presence of definite RBM in young adult knees was observed in females only. Definite RBM was associated with overweight measures, and the modest association with knee pain may not be causally related.

Pathogen infection risk to recreational water users, associated with surface waters impacted by de facto and indirect potable reuse activities.

Water deficit, exacerbated by global population increases and climate change, necessitates the investigation of alternative non-traditional water sources to augment existing supplies. Indirect potable reuse (IPR) represents a promising alternative water source in water-stressed regions. Of high concern is the presence of pathogenic microorganisms in wastewater, such as enteric viruses, protozoa and bacteria. Therefore, a greater understanding of the potential impact to human health is required. The aim of this research was to use a quantitative microbial risk assessment (QMRA) approach to calculate the probability of potential pathogen infection risk to the public in surface waters used for a range of recreational activities under scenarios: 1) existing de facto wastewater reuse conditions; 2) after augmentation with conventionally treated wastewater; and 3) after augmentation with reclaimed wastewater from proposed IPR schemes. Forty-four 31 l samples were collected from river sites and a coastal wastewater treatment works from July 2016-May 2017. Concentrations of faecal indicator organisms (enterococci, faecal coliforms, somatic coliphages and Bacteroides phages) determined using culture-based approaches and selected pathogens (adenovirus, Salmonella and Cryptosporidium) determined using molecular approaches (qPCR) were used to inform QMRA. The mean probability of infection from adenovirus under de facto conditions was high (>0.90) for all recreational activities, per single event. The risk of adenovirus and Cryptosporidium infection increased under augmentation scenario (2) (mean probability 0.95-1.00 and 0.01-0.06 per single event, respectively). Adenovirus and Cryptosporidium infection risk decreased under reclaimed water augmentation scenario (3) (mean probability <0.79, excluding swimming, which remained 1.00 and <0.01 per single event, respectively). Pathogen reduction after reclaimed water augmentation in surface waters impacted by de facto reuse, provides important evidence for alternative water supply option selection. As such, this evidence may inform water managers and the public of the potential benefits of IPR and improve acceptance of such practices in the future.

Effect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial.

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T12 -S1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research.

Hypointense signals in the infrapatellar fat pad assessed by magnetic resonance imaging are associated with knee symptoms and structure in older adults: a cohort study.

BACKGROUND: There are few clinical and epidemiological studies reporting the association between abnormal changes within the IPFP and knee osteoarthritic changes. This study aims to describe the associations between hypointense signals in the infrapatellar fat pad (IPFP) and knee structural change and symptoms in older adults. METHODS: Participants (n = 874) were selected randomly from local community and followed up 2.7 years later (range 2.6-3.3 years). T1- or T2-weighted fat-suppressed magnetic resonance imaging (MRI) was assessed for IPFP hypointense signal, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic osteoarthritis was assessed using the OARSI atlas. RESULTS: Cross-sectionally, hypointense signals in the IPFP were significantly associated with a higher risk of knee cartilage defects at all sites, tibiofemoral BMLs and knee pain in multivariable analyses. Longitudinally, baseline signal abnormalities were significantly and positively associated with increases in knee cartilage defects (OR: 2.27, 95 % CI: 1.61-3.21), BMLs (OR: 1.91, 95 % CI: 1.39-2.62), and knee pain (OR: 1.36, 95 % CI: 1.05-1.76) in multivariable analyses. The associations with cartilage defects remained significant after adjustment for BMLs, but the associations with BMLs and knee pain decreased in magnitude or became non-significant after further adjustment for cartilage defects. CONCLUSIONS: Hypointense signals in the IPFP were associated primarily with increased knee cartilage defects and also with BMLs and knee symptoms in cross-sectional and longitudinal analyses, suggesting the abnormality represented by this signal has a potentially important role in osteoarthritis progression.

Correlates of knee bone marrow lesions in younger adults.

BACKGROUND: Subchondral bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA) and are associated with pain and structural progression in knee OA. However, little is known about clinical significance and determinants of BMLs of the knee joint in younger adults. We aimed to describe the prevalence and environmental (physical activity), structural (cartilage defects, meniscal lesions) and clinical (pain, stiffness, physical dysfunction) correlates of BMLs in younger adults and to determine whether cholesterol levels measured 5 years prior were associated with current BMLs in young adults. METHODS: Subjects broadly representative of the Australian young adult population (n = 328, aged 31-41 years, female 48.7 %) underwent T1- and proton density-weighted fat-suppressed magnetic resonance imaging (MRI) in their dominant knee. BMLs, cartilage defects, meniscal lesions and cartilage volume were measured. Knee pain was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Cholesterol levels including high-density lipoprotein (HDL) were assessed 5 years prior to MRI. RESULTS: The overall prevalence of BML was 17 % (grade 1: 10.7 %, grade 2: 4.3 %, grade 3: 1.8 %). BML was positively associated with increasing age and previous knee injury but not body mass index. Moderate physical activity (prevalence ratio (PR):0.93, 95 % CI: 0.87, 0.99) and HDL cholesterol (PR:0.36, 95 % CI: 0.15, 0.87) were negatively associated with BML, while vigorous activity (PR:1.02, 95 % CI: 1.01, 1.03) was positively associated with medial tibiofemoral BMLs. BMLs were associated with more severe total WOMAC knee pain (>5 vs ≤5, PR:1.05, 95 % CI: 1.02, 1.09) and WOMAC dysfunction (PR:1.75, 95 % CI: 1.07, 2.89), total knee cartilage defects (PR:2.65, 95 % CI: 1.47, 4.80) and total meniscal lesion score (PR:1.92, 95 % CI: 1.13, 3.28). CONCLUSIONS: BMLs in young adults are associated with knee symptoms and knee structural lesions. Moderate physical activity and HDL cholesterol are beneficially associated with BMLs; in contrast, vigorous physical activity is weakly but positively associated with medial tibiofemoral BMLs.

Cross-sectional and Longitudinal Associations between Knee Joint Effusion Synovitis and Knee Pain in Older Adults.

OBJECTIVE: To describe the cross-sectional and longitudinal associations between knee regional effusion synovitis and knee pain in older adults. METHODS: Data from a population-based random sample (n = 880, mean age 62 yrs, 50% women) were used. Baseline knee joint effusion synovitis was graded (0-3) using T2-weighted magnetic resonance imaging (MRI) in the suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess. Effusion synovitis of the whole joint was defined as a score of ≥ 2 in any subregion. Other knee structural (including cartilage, bone marrow, and menisci) lesions were assessed by MRI at baseline. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire at baseline and 2.6 years later. Multivariable analyses were performed after adjustment for age, sex, body mass index, and other structural lesions. RESULTS: The prevalence of effusion synovitis was 67%. Suprapatellar pouch effusion synovitis was significantly and independently associated with increased total and nonweight-bearing knee pain in both cross-sectional and longitudinal analyses (for an increase in total knee pain of ≥ 5, RR 1.26 per grade, 95% CI 1.04-1.52), and increased weight-bearing knee pain in longitudinal analysis only. Effusion synovitis in posterior femoral recess and central portion were independently associated with increases in nonweight-bearing pain (RR 1.63 per grade, 95% CI 1.32-2.01 and RR 1.29 per grade, 95% CI 1.01-1.65, respectively) in longitudinal analyses only. CONCLUSION: Knee joint effusion synovitis has independent associations with knee pain in older adults. Suprapatellar pouch effusion synovitis is associated with nonweight-bearing and weight-bearing knee pain, while posterior femoral recess and central portion effusion synovitis are only associated with nonweight-bearing pain.

Association between MRI-detected knee joint regional effusion-synovitis and structural changes in older adults: a cohort study.

OBJECTIVE: To describe the cross-sectional and longitudinal associations between knee regional effusion-synovitis and structural changes in older adults. METHODS: A total of 977 subjects were randomly selected from the local community (mean 62 years, 50% female) at baseline and 404 were followed up 2.6 years later. T2-weighted MRI was used to assess knee effusion-synovitis in four subregions: suprapatellar pouch, central portion, posterior femoral recess and subpopliteal recess. Knee cartilage defects, cartilage volume and bone marrow lesions (BMLs) were measured using MRI at baseline and follow-up. RESULTS: Cross-sectionally, effusion-synovitis in most subregions was significantly associated with a higher risk of cartilage defects, BMLs and reduced cartilage volume. Longitudinally, suprapatellar pouch effusion-synovitis at baseline predicted an increase in cartilage defects (p<0.01), loss of cartilage volume (p=0.04) and an increase in BMLs (p=0.02) in multivariable analyses. The significant associations of effusion-synovitis with cartilage volume and BMLs disappeared after adjustment for cartilage defects. Effusion-synovitis in whole knee joint (p<0.01) and subpopliteal recess (p<0.05) was consistently associated with longitudinal changes in cartilage defects but not in cartilage volume and BMLs. CONCLUSIONS: There are independent associations between knee joint effusion-synovitis and knee cartilage defects in both cross-sectional and longitudinal analyses, suggesting a potential causal relationship. The associations of effusion-synovitis with BMLs and cartilage volume were largely dependent on cartilage defects, suggesting potential causal pathways.

Signal intensity alteration in the infrapatellar fat pad at baseline for the prediction of knee symptoms and structure in older adults: a cohort study.

OBJECTIVE: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults. METHODS: A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed. RESULTS: In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses. CONCLUSIONS: IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA.

Quantitative Assessment of Knee Effusion-Synovitis in Older Adults: Association With Knee Structural Abnormalities.

OBJECTIVE: To describe the natural history of quantitatively measured knee effusion-synovitis and the longitudinal associations between effusion-synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults. METHODS: A total of 406 subjects (with a mean age of 63 years, 50% women) were randomly selected at baseline and followed up 2.7 years later. T2- or T1-weighted fat saturation magnetic resonance imaging was used to assess knee effusion-synovitis maximal area, cartilage defects, cartilage volume, bone marrow lesions, and meniscal pathology at baseline and follow-up. Multivariable generalized linear regression was performed to analyze the associations between the maximal area of effusion-synovitis and other joint structural factors after adjustment for age, sex, body mass index, tibial bone area, and/or radiographic osteoarthritis (OA). RESULTS: Over 2.7 years of follow-up, the size of effusion-synovitis increased in 29%, remained stable in 50%, and decreased in 22% of the participants. Baseline effusion-synovitis maximal area was significantly associated with changes in knee cartilage defects (ß = 0.18 [95% confidence interval (95% CI)] 0.07, 0.29), bone marrow lesions (ß = 0.17 [95% CI 0.05, 0.30]), and cartilage volume (ß = -0.40 [95% CI -0.71, -0.09]) but not with change in meniscal pathology. In contrast, baseline structural measures were not associated with change or increase in effusion-synovitis maximal area. CONCLUSION: Our findings indicate that knee effusion-synovitis is not static in older adults. It is predictive of, but not predicted by, other structural abnormalities, suggesting a potential role in early knee OA changes.

Clinical diagnosis of medial plica syndrome of the knee: a prospective study.

Clinical diagnosis of symptomatic medial plica that causes anteromedial knee pain is poorly defined in the literature; therefore, arthroscopy is considered to be the gold standard for diagnosing this condition. We report our system of clinical diagnosis for medial plica syndrome that is based on patient history and our criteria for clinical examination. This prospective study included 48 symptomatic patients (66 knees) with clinical suspicion of pathological medial plica based on five essential and four desirable criteria. All patients underwent arthroscopic examination to confirm or disprove the clinical diagnosis and also treatment. Arthroscopy confirmed the clinical diagnosis of medial plicae in 44 patients (62 knees) for a diagnostic accuracy of 91.7% (95% confidence interval [CI]: 80% to 97.7%) and sensitivity of 100% (95% CI: 92% to 100%). The 44 patients with pathological medial plicae at arthroscopy were treated by arthroscopic resection. Thirty-nine patients (55 knees) showed satisfactory outcome after arthroscopy (95% CI: 75.4%, 96.2%). Our method of clinical diagnosis of pathological medial plica is simple, inexpensive, noninvasive, and reliable. We conclude arthroscopy is successful in treating this condition.