Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Association between hamstring coactivation during isokinetic quadriceps strength testing and knee cartilage worsening over 24 months.

OBJECTIVE: This study aimed to determine longitudinal associations, including sex-specific differences, between greater knee flexor antagonist coactivation and worsening cartilage morphology in knees with or at risk for osteoarthritis (OA). DESIGN: Baseline measurements were collected at the 60-month visit of a longitudinal osteoarthritis study following community-dwelling participants (MOST). Knee flexor and extensor muscle activity were measured with surface electromyography during a maximal isokinetic knee extension task. MRI analyzed knee cartilage morphology at baseline and 24-month follow-up. Multivariable adjusted logistic regression models were used to assess associations between coactivation level and cartilage morphology worsening. RESULTS: Analysis of 373 women (mean ± SD age 67.4 ± 7.3 years and BMI 29.7 ± 5.0 kg/m2) and 240 men (66.5 ± 7.8 years and 29.9 ± 4.5 kg/m2) revealed that women had greater medial (P < 0.001), lateral (P < 0.001), and combined (P < 0.001) hamstring coactivation than men. In both sexes, combined hamstring coactivation was associated with patellofemoral cartilage morphology worsening [1.23 (1.02, 1.49)] and to a less significant degree with whole knee cartilage morphology worsening [1.21 (0.98, 1.49)]. In men, greater combined hamstring coactivation was associated with increased risk for whole knee [1.59 (1.06, 2.39)] and patellofemoral [1.38 (1.01, 1.88)] cartilage morphology worsening and point estimates suggested association between medial hamstring coactivation and medial tibiofemoral cartilage morphology worsening. No significant associations were detected between greater hamstring coactivation and cartilage morphology worsening in women. CONCLUSIONS: These findings suggest a longitudinal relationship between antagonist hamstring coactivation during isokinetic knee extensor testing and worsening of cartilage morphology over 24 months in men with or at risk for knee OA.

Clinical value of weight-bearing CT and radiographs for detecting patellofemoral cartilage visualized by MRI in the MOST study.

OBJECTIVE: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI. DESIGN: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared. RESULTS: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good. CONCLUSION: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint.

Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).

OBJECTIVE: To compare ground reaction force patterns (GRF) during walking among legs defined by presence or absence of knee pain and/or radiographic knee osteoarthritis (ROA). METHOD: Principal component analysis extracted major modes of variation (PCs) in GRF data from the Multicenter Osteoarthritis Study during self-paced walking. Legs were categorized as pain + ROA (n = 168), ROA only (n = 303), pain only (n = 476), or control (n = 1877). Relationships between group and GRF PCs were examined using Generalized Estimating Equations, adjusted for age, sex, body mass index, race, and clinic site with and without additional adjustment for gait speed. RESULTS: With or without speed adjustment, pain + ROA had flatter vertical GRF waveforms than control (speed adjusted PC2 difference [95%CI]: -66 [-113,-20]), pain + ROA and ROA only had higher lateral GRF at impact and greater mid-stance medial GRF than control (speed adjusted PC3 difference: 9 [3,16] and 6 [2,10], respectively), and ROA only had higher early vs late medial GRF than control (speed adjusted PC2 difference: 7 [2,13]). Pain only had flatter vertical GRF waveforms and a smaller difference between anterior and posterior GRF than control only without speed adjustment. CONCLUSION: In this large sample, sustained mid-stance loading and higher impact loads were identified in legs with ROA or ROA and pain, even when adjusting for differences in gait speed and other confounders. While it remains to be seen whether these features precede or result from ROA and pain, the presence of these patterns in the speed-adjusted models could have implications on gait interventions aimed to change joint loading.

The relation of peripheral and central sensitization to muscle co-contraction: the MOST study.

OBJECTIVE: To examine the relation of pain sensitization to altered motor activity in knee OA as assessed by hamstrings muscle co-contraction during maximal effort knee extension. DESIGN: Medial, lateral, and overall hamstring co-contraction was assessed in the Multicenter Osteoarthritis (MOST) Study cohort using electromyography during isokinetic knee extension at 60°/second. Mechanical temporal summation of pain (TS) was assessed at the right wrist and pressure pain thresholds (PPT) were assessed at the patellae; PPTs were categorized into sex-specific tertiles. Muscle co-contraction was categorized into age- and sex-specific tertiles. We evaluated the relation of measures of sensitization to muscle co-contraction using a generalized logistic regression model. RESULTS: 1633 participants were included: mean age and BMI was 67.3 ± 7.7 years and 30.3 ± 5.6 kg/m2, respectively; 58% were female. Presence of TS was associated with higher overall (OR 1.3, 95% confidence interval (CI) (1.0-1.8)), medial (1.4 (1.0-1.9), and lateral (1.3 (1.0, 1.9)) hamstring co-contraction. The lowest PPT tertile (greater sensitivity) was associated with higher overall (1.5 (1.0, 2.3)) and medial (1.5 (1.0, 2.3)) hamstring co-contraction compared with those in the highest PPT tertile. CONCLUSION: Greater pain sensitization, as assessed by presence of TS at the wrist and low patellar PPT, was associated with greater overall and medial hamstring co-contraction during knee extension. This provides support to the possibility that peripheral and/or central nervous system alterations may not only affect pain sensitivity, but also motor function.

Muscle strength, physical performance and physical activity as predictors of future knee replacement: a prospective cohort study.

OBJECTIVE: To investigate associations between lower levels of muscle strength, physical performance and physical activity and the risk of knee replacement (KR) in older adults with frequent knee pain. METHOD: Participants from the Multicenter Osteoarthritis Study (MOST) with knee pain on most of the past 30 days at baseline were included (n = 1257; mean (SD) age of 62.2 (8.2)). We examined the association between (1) baseline peak isokinetic knee extensor strength, (60°/sec, maximum out of four trials), (2) best time to stand in timed chair stand (2 trials of five repetitions), and (3) baseline Physical Activity Scale for the Elderly score (PASE) with incident KR between baseline and the 84-month follow-up. RESULTS: 1252 (99.6%) participants (1682 knees) completed the follow-up visits. 331 participants (394 knees) underwent a KR during the 84 months (229 women and 102 men). The crude analysis demonstrated a decreased risk of KR in women (P < 0.0001) with higher knee extensor strength (Hazard Ratio (HR; 95% CI) 0.99 (0.98-0.99)). The risk remained significant (P = 0.03) when adjusting for age, BMI, race, clinic site, education, occupation, previous knee injury, previous knee surgery, and WOMAC pain (HR (95% CI) 0.99 (0.99-1.00)), but not when adjusting for Kellgren-Lawrence grade (P = 0.97). CONCLUSION: Lower levels of chair stand performance and self-reported physical activity are not associated with an increased risk of KR within 7 years, while the independent effect of knee extensor strength on risk for KR in women is non-significant after adjusting for radiographic severity.

Comparison of the extent to which total hip and total knee arthroplasty restore patient-reported physical function.

OBJECTIVE: To evaluate the extent to which elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) for osteoarthritis (OA) restore normal patient-reported physical function in men and women. METHODS: Pain and physical function (WOMAC-PF) were prospectively measured pre- and post-operatively. The relationship between surgical procedure and achieving physical function equivalent to age and sex-matched adults with no hip or knee joint problems was modeled using sex-specific logistic regression. Percent change in function was also compared between groups using sex-specific generalized linear models adjusted for age, BMI, pain, comorbid conditions, time from surgery, and subsequent surgery. RESULTS: Individuals with pre- and post-operative WOMAC data were classified exclusively into either THA (287M:306F) or TKA (239M:424F) groups. The median follow-up was 476 (THA) and 474 (TKA) days for men, and 495 (THA) and 526 (TKA) days for women. MAIN OUTCOME: women with THA compared with TKA were more likely to achieve a normal level of postoperative PF while there were no significant differences between procedures in men. Additional analyses: we found slightly lower preoperative PF in THA compared with TKA. This difference resolved postoperatively in men, but women who underwent THA reported greater improvement and better PF than those who had TKA. CONCLUSION: In women, THA results in greater improvement in WOMAC-PF at approximately 1-year follow-up and better approximates physical function of community-dwelling older adults without OA than TKA does. In contrast, in men, a lack of between-group post-operative WOMAC-PF differences suggests that procedures result in a similar degree of improvement.

Changes in patellofemoral and tibiofemoral joint cartilage damage and bone marrow lesions over 7 years: the Multicenter Osteoarthritis Study.

OBJECTIVES: To investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years. METHODS: The Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage. RESULTS: Among 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full-thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full-thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full-thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage. CONCLUSIONS: Most knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ.

Baseline trabecular bone and its relation to incident radiographic knee osteoarthritis and increase in joint space narrowing score: directional fractal signature analysis in the MOST study.

PURPOSE: To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score. METHODS: The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren-Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ≤ 1) at baseline were assessed for incident OA (KL ≥ 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders. RESULTS: Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales. CONCLUSION: Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.

Validity and sensitivity to change of three scales for the radiographic assessment of knee osteoarthritis using images from the Multicenter Osteoarthritis Study (MOST).

OBJECTIVES: The purpose of this study was to assess the concurrent validity and sensitivity to change of three knee osteoarthritis (OA) grading scales. The Kellgren-Lawrence (KL) and the Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) grading scales are well-established. The third scale, the compartmental grading scale for OA (CG) is a novel scale which grades JSN, femoral osteophytes, tibial erosion and subluxation to create a total score. METHODS: One sample of 72 posteroanterior (PA) fixed-flexion radiographs displaying mild to moderate knee OA was selected from the Multicenter Osteoarthritis Study (MOST) to study validity. A second sample of 75 radiograph pairs, which showed an increase in OA severity over 30 months, was selected to study sensitivity to change. The three radiographic grading scales were applied to each radiograph in both samples. Spearman's rank correlation coefficients were used to correlate the radiographic grades and the change in grades over 30 months with a Whole-organ Magnetic Resonance Imaging Score (WORMS)-based composite score which included five articular features of knee OA. RESULTS: Correlations between the KL, OARSI JSN and CG grading scales and the magnetic resonance image (MRI)-based score were 0.836, 0.840 and 0.773 (P < 0.0001) respectively while correlations between change in the radiographic grading scales and change in the MRI-based score were 0.501, 0.525 and 0.492 (P < 0.0001). CONCLUSIONS: All three radiographic grading scales showed high validity and are suitable to assess knee OA severity. They showed moderate sensitivity to change; therefore caution should be taken when using ordinal radiographic grading scales to monitor knee OA over time.

The association between antagonist hamstring coactivation and episodes of knee joint shifting and buckling.

OBJECTIVE: Hamstring coactivation during quadriceps activation is necessary to counteract the quadriceps pull on the tibia, but coactivation can be elevated with symptomatic knee osteoarthritis (OA). To guide rehabilitation to attenuate risk for mobility limitations and falls, this study evaluated whether higher antagonistic open kinetic chain hamstring coactivation is associated with knee joint buckling (sudden loss of support) and shifting (a sensation that the knee might give way). DESIGN: At baseline, median hamstring coactivation was assessed during maximal isokinetic knee extensor strength testing and at baseline and 24-month follow-up, knee buckling and shifting was self-reported. Associations between tertiles of co-activation and knee (1) buckling, (2) shifting and (3) either buckling or shifting were assessed using logistic regression, adjusted for age, sex, knee OA and pain. RESULTS: 1826 participants (1089 women) were included. Mean ± SD age was 61.7 ± 7.7 years, BMI was 30.3 ± 5.5 kg/m(2) and 38.2% of knees had OA. There were no consistent statistically significant associations between hamstring coactivation and ipsilateral prevalent or incident buckling or the combination of buckling and shifting. The odds ratios for incident shifting in the highest in comparison with the lowest tertile of coactivation had similar magnitudes in the combined and medial hamstrings, but only reached statistical significance for lateral hamstring coactivation, OR(95%CI) 1.53 (0.99, 2.36). CONCLUSIONS: Hamstring coactivation during an open kinetic chain quadriceps exercise was not consistently associated with prevalent or incident self-reported knee buckling or shifting in older adults with or at risk for knee OA.

The relation of MRI-detected structural damage in the medial and lateral patellofemoral joint to knee pain: the Multicenter and Framingham Osteoarthritis Studies.

OBJECTIVE: To examine the relation of cartilage loss and bone marrow lesions (BMLs) in the medial and lateral patellofemoral joint (PFJ) to knee pain. METHODS: We categorized the location of full-thickness cartilage loss and BMLs in the PFJ on knee magnetic resonance imaging (MRIs) from the Multicenter Osteoarthritis (MOST) and Framingham Osteoarthritis (FOA) Studies as no damage, isolated medial, isolated lateral, or both medial and lateral (mixed). We determined the relation of MRI lesions in each PFJ region to prevalent knee pain. Differences in knee pain severity were compared among categories of PFJ full-thickness cartilage loss and BMLs using quantile regression. RESULTS: In MOST (n = 1137 knees), compared with knees without full-thickness cartilage loss, knees with isolated lateral or mixed PFJ full-thickness cartilage loss had 1.9 (1.3, 2.8) and 1.9 (1.2, 2.9) times the odds of knee pain, respectively, while isolated medial cartilage loss had no association with knee pain. BMLs in both the medial and lateral PFJ had 1.5 (1.1, 2.0) times the odds of knee pain compared with knees without BMLs. Knee pain severity was lowest in knees with isolated medial PFJ cartilage loss or BMLs. In FOA (n = 934 knees), neither isolated medial nor lateral cartilage loss was associated with knee pain, whereas isolated BMLs in either region were associated with pain. CONCLUSIONS: Results were not completely concordant but suggest that knee pain risk and severity is greatest with cartilage loss isolated to (MOST) or inclusive of (MOST and FOA) the lateral PFJ. While BMLs in either the medial or lateral PFJ are related to pain.

Association of hip and pelvic geometry with tibiofemoral osteoarthritis: multicenter osteoarthritis study (MOST).

OBJECTIVE: Lateral tibiofemoral osteoarthritis (OA) is overall less common than medial tibiofemoral OA, but it is more prevalent in women. This may be explained by sex differences in hip and pelvic geometry. The aim of this study is to explore sex differences in hip and pelvic geometry and determine if such parameters are associated with the presence of compartment-specific knee OA. METHODS: This case-control study reports on 1,328 hips/knees from 664 participants and is an ancillary to the Multicenter Osteoarthritis Study (MOST). Of the 1,328 knees, 219 had lateral OA, 260 medial OA, and 849 no OA. Hip and pelvic measurements were taken from full-limb radiographs on the ipsilateral side of the knee of interest. After adjusting for covariates, means were compared between sexes and also between knees with medial and lateral OA vs no OA using separate regression models. RESULTS: Women were shown to have a reduced femoral offset (FO) (mean 40.9 mm vs 45.9 mm; P = 0.001) and more valgus neck-shaft angle (mean 128.4° vs 125.9°; P < 0.001) compared to men. Compared to those with no OA, knees with lateral OA were associated with a reduced FO (P = 0.012), increased height of hip centre (HHC) (P = 0.003), more valgus neck-shaft angle (P = 0.042), and increased abductor angle (P = 0.031). Knees with medial OA were associated with a more varus neck-shaft angle (P = 0.043) and a decreased abductor angle (P = 0.003). CONCLUSION: These data suggest anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA.

The impact of knee instability with and without buckling on balance confidence, fear of falling and physical function: the Multicenter Osteoarthritis Study.

OBJECTIVE: Knee buckling, in which a knee gives way during weight-bearing, is common in people with knee pain and knee osteoarthritis (OA), but little is known about the prevalence of sensations of knee instability, slipping or shifting in which the knee does not actually buckle, or of the psychosocial and physical consequences of these symptoms. DESIGN: We asked participants in the Multicenter Osteoarthritis Study (MOST) separately about episodes of knee buckling and sensations of knee instability without buckling in the past 3 months, and assessed fear of falling, poor balance confidence (Activities-specific Balance Confidence (ABC) Scale ≤ 67/100), activity limitation due to concern about buckling, and poor physical function (Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function ≥ 28/68). We used Poisson regression to estimate prevalence ratios (PRs) for cross-sectional associations of buckling and sensations of instability without buckling with these outcomes, adjusting for confounders. RESULTS: Of 2120 participants (60% female, 40% ≥ 65 years, mean Body mass index (BMI): 31 kg/m258), 18% reported buckling, 27% had sensations of knee instability without buckling, and 9% reported both symptoms. Buckling and sensations of instability without buckling were each significantly associated with fear of falling, poor balance confidence, activity limitations, and poor WOMAC physical function. Subjects who reported both buckling and instability without buckling and those with at least two buckling episodes (15%) had the strongest association with poor outcomes. CONCLUSIONS: Knee buckling and especially sensations of knee instability without buckling were common and each was significantly associated with fear of falling, poor balance confidence, activity limitations, and poor physical function.

Examining sex differences in knee pain: the multicenter osteoarthritis study.

OBJECTIVE: To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). DESIGN AND METHODS: A cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren-Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). RESULTS: Women reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21-0.31, P < 0.0001-0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16-0.22, P < 0.0001-0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10-0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32-0.52, P < 0.0001-0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45-0.62, P = 0.0006-0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31-0.57, P = 0.0013-0.0361). Results using WOMAC were similar. CONCLUSIONS: Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences.

The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.

OBJECTIVE: To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. RESULTS: Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). CONCLUSION: Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus.

We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection.

The longitudinal relationship between thigh muscle mass and the development of knee osteoarthritis.

OBJECTIVE: Greater quadriceps strength has been found to reduce risk for symptomatic knee osteoarthritis (SxKOA) and knee joint space narrowing (JSN). However, this finding could relate to muscle mass or activation pattern. The purpose of this study was to assess whether greater thigh muscle mass protects against (1) incident radiographic (RKOA), (2) incident SxKOA or (3) worsening of knee JSN by 30-month follow-up. DESIGN: Multicenter Osteoarthritis (MOST) study participants, who underwent dual-energy X-ray absorptiometry (DXA) at the Iowa site were included. Thigh muscle mass was calculated from DXA image sub-regions. Sex-stratified, knee-based analyses controlled for incomplete independence between limbs within subjects. The effect of thigh lean mass and specific strength as predictors of ipsilateral RKOA, SxKOA and worsening of JSN were assessed, while controlling for age, body mass index (BMI), and history of knee surgery. RESULTS: A total of 519 men (948 knees) and 784 women (1453 knees) were included. Mean age and BMI were 62 years and 30 kg/m(2). Thigh muscle mass was not associated with risk for RKOA, SxKOA or knee JSN. However, in comparison with the lowest tertile, those in the highest and middle tertiles of knee extensor specific strength had a lower risk for SxKOA and JSN [odds ratio (OR) 0.29-0.68]. CONCLUSIONS: Thigh muscle mass does not appear to confer protection against incident or worsening knee OA. These findings suggest that future studies of risk for knee OA should focus on the roles of knee extensor neuromuscular activation and muscle physiology, rather than the muscle mass.

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months.

OBJECTIVE: As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. DESIGN: This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. RESULTS: Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). CONCLUSIONS: Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.