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1.  Spiking of the tibial tubercles--a radiological feature of osteoarthritis? 
Annals of the Rheumatic Diseases  1996;55(2):105-108.
OBJECTIVE: To determine whether 'spiking' or angulation of the tibial tubercle is associated with other radiographic markers of osteoarthritis (OA) or pain in the knee joint, and could be taken as a reliable marker for early OA, in a large general population sample. METHODS: A total of 950 women from the Chingford general population survey underwent anteroposterior extended weight bearing radiography of the knees. Angulation of the tip of the medial and lateral tubercles, and height of the tubercles above the tibial plateau were measured. These measures were compared with standard radiographic indices including qualitative Kellgren and Lawrence global score, individual scores of osteophytes and joint space narrowing, and pain score. Intraobserver and interobserver reproducibility for assessment of spiking was tested in a subgroup of 50 films using two observers and two readings. Tibial spiking (angulation and height) was defined for this study as the top 10th centile for the whole population. Patients with normal radiographs (Kellgren and Lawrence grade 0) were allocated to quartile groups on the basis of spiking to define severity. Odds ratios were then calculated for the association of spiking and knee pain. RESULTS: The majority of the measures of tibial spiking were highly reproducible. There was a significant correlation between tibial spike angulation and the presence of osteophytes, but not joint space narrowing. The correlations for spike height with osteophytes and joint space narrowing were poor. There was an association between spike angulation at the lateral tubercle and reported knee pain (odds ratio 1.45 (95% confidence interval 1.03 to 2.03)) after adjustment for age, body mass index, and Kellgren and Lawrence score. There was no association between medial spike angulation or spike height and pain. Among the 950 women, 683 (72%) had normal radiographs (Kellgren and Lawrence = 0); in this group there was a similar association between pain and lateral spike angulation, but not medial spike angulation or spike height. CONCLUSIONS: Tibial spiking is associated with the presence of knee osteophytes and is reproducible, but does not have a strong independent relationship with knee pain. In patients with normal radiographs there is no useful correlation between tibial spiking and pain. Isolated tibial spiking is not a reliable sign of early knee OA, and should not routinely be reported.
PMCID: PMC1010103  PMID: 8712859
2.  Reduced functional performance in the lower extremity predicted radiographic knee osteoarthritis five years later 
Annals of the Rheumatic Diseases  2004;63(4):402-407.
Background: Reduced quadriceps strength is an early finding in subjects with knee osteoarthritis, but it is not clear whether it is a cause or a consequence of knee osteoarthritis.
Objective: To determine whether reduced functional performance in the lower extremity predicts the incidence or progression of radiographic knee osteoarthritis.
Design: Prospective, epidemiological, population based cohort study.
Patients: 148 subjects (62 women), aged 35–54 (mean 44.8), with chronic knee pain from a population based cohort.
Measurements: Predictors analysed were age, sex, body mass index, baseline knee pain, and three tests of lower extremity functional performance: maximum number of one-leg rises from sitting, time spent walking 300 m, and timed standing on one leg. Weightbearing tibiofemoral knee radiographs were obtained at baseline and after 5 years (median 5.1, range 4.2–6.1), and classified according to Kellgren and Lawrence as no osteoarthritis (Kellgren and Lawrence = 0, n = 94) or prevalent osteoarthritis (Kellgren and Lawrence ⩾1, n = 54).
Results: Fewer one-leg rises (median 17 v 25) predicted incident radiographic osteoarthritis five years later (OR 2.6, 95% CI 1.1 to 6.0). The association remained significant after controlling for age, sex, body mass index, and pain. No significant predictor of radiographic progression in the group with prevalent osteoarthritis was found.
Conclusion: Reduced functional performance in the lower extremity predicted development of radiographic knee osteoarthritis 5 years later among people aged 35–55 with chronic knee pain and normal radiographs at baseline. These findings suggest that a test of one-leg rises may be useful, and interventions aimed at improving functional performance may be protective against development of knee osteoarthritis.
PMCID: PMC1754965  PMID: 15020334
3.  Clinical classification criteria for knee osteoarthritis: performance in the general population and primary care 
Annals of the Rheumatic Diseases  2006;65(10):1363-1367.
Doubts have been expressed about the performance of the American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis when applied in the general population.
To investigate whether the distribution of population subgroups and underlying disease severity might explain the performance of these criteria in the population setting.
Population‐based cross‐sectional study. 819 adults aged ⩾50 years reporting knee pain in the last 12 months were clinically assessed by research therapists using standardised protocols and blinded to radiographic status. All participants underwent plain radiography of the knees, scored by a single reader blinded to clinical status. The relationship between fulfilling the ACR clinical classification criteria for knee osteoarthritis and the presence of symptomatic radiographic knee osteoarthritis was summarised for the sample as a whole and within subgroups.
Radiographic osteoarthritis was present in 539 participants (68%) and symptomatic radiographic knee osteoarthritis in 259 (33%). 238 participants (30%) fulfilled the ACR clinical criteria for knee osteoarthritis. Agreement between the ACR clinical criteria and symptomatic radiographic knee osteoarthritis was low (sensitivity 41%; specificity 75%; positive predictive value 44%; negative predictive value 72%). Sensitivity and specificity did not vary markedly between population subgroups, although they were influenced by the underlying severity of radiographic osteoarthritis.
The ACR clinical criteria seem to reflect later signs in advanced disease. Other approaches may be needed to identify early, mild osteoarthritis in the general population and primary care.
PMCID: PMC1798313  PMID: 16627539
4.  Isometric Quadriceps Strength in Women with Mild, Moderate, and Severe Knee Osteoarthritis 
Quadriceps weakness is a common clinical sign in persons with moderate-to-severe osteoarthritis and results in physical disability; however, minimal data exist to establish whether quadriceps weakness is present in early stages of the disease. Therefore, our purpose was to determine whether quadriceps weakness was present in persons with early radiographic and cartilaginous evidence of osteoarthritis. Further, we sought to determine whether quadriceps strength decreases as osteoarthritis severity increases.
Three hundred forty-eight women completed radiologic and magnetic resonance imaging evaluation, in addition to strength testing. Anterior-posterior radiographs were graded for tibiofemoral osteoarthritis severity using the Kellgren-Lawrence scale. Scans from magnetic resonance imaging were used to assess medial tibiofemoral and patellar cartilage based on a modification of the Noyes scale. The peak knee extension torque recorded was used to represent strength.
Quadriceps strength (Nm/kg) was 22% greater in women without radiographic osteoarthritis than in women with osteoarthritis (P < 0.05). Quadriceps strength was also greater in women with Noyes’ medial tibial and femoral cartilage scores of 0 when compared in women with Noyes’ grades 2 and 3–5 (P ≤ 0.05).
Women with early evidence of osteoarthritis had less quadriceps strength than women without osteoarthritis as defined by imaging.
PMCID: PMC3294452  PMID: 20463561
Knee Extensors; Muscle; Joint Disease
5.  Incidental Meniscal Findings on Knee MRI in Middle-Aged and Elderly Persons 
The New England journal of medicine  2008;359(11):1108-1115.
Magnetic resonance imaging (MRI) of the knee is often performed in patients who have knee symptoms of unclear cause. When meniscal tears are found, it is commonly assumed that the symptoms are attributable to them. However, there is a paucity of data regarding the prevalence of meniscal damage in the general population and the association of meniscal tears with knee symptoms and with radiographic evidence of osteoarthritis.
We studied persons from Framingham, Massachusetts, who were drawn from census-tract data and random-digit telephone dialing. Subjects were 50 to 90 years of age and ambulatory; selection was not made on the basis of knee or other joint problems. We assessed the integrity of the menisci in the right knee on 1.5-tesla MRI scans obtained from 991 subjects (57% of whom were women). Symptoms involving the right knee were evaluated by questionnaire.
The prevalence of a meniscal tear or of meniscal destruction in the right knee as detected on MRI ranged from 19% (95% confidence interval [CI], 15 to 24) among women 50 to 59 years of age to 56% (95% CI, 46 to 66) among men 70 to 90 years of age; prevalences were not materially lower when subjects who had had previous knee surgery were excluded. Among persons with radiographic evidence of osteoarthritis (Kellgren–Lawrence grade 2 or higher, on a scale of 0 to 4, with higher numbers indicating more definite signs of osteoarthritis), the prevalence of a meniscal tear was 63% among those with knee pain, aching, or stiffness on most days and 60% among those without these symptoms. The corresponding prevalences among persons without radiographic evidence of osteoarthritis were 32% and 23%. Sixty-one percent of the subjects who had meniscal tears in their knees had not had any pain, aching, or stiffness during the previous month.
Incidental meniscal findings on MRI of the knee are common in the general population and increase with increasing age.
PMCID: PMC2897006  PMID: 18784100
6.  Role of radiography in predicting progression of osteoarthritis of the hip: prospective cohort study 
BMJ : British Medical Journal  2005;330(7501):1183.
Objectives To investigate which variables identify people at high risk of progression of osteoarthritis of the hip.
Design Population based cohort study.
Setting Ommoord district in Rotterdam, Netherlands.
Participants 1904 men and women aged 55 years and older from the Rotterdam study were selected on the basis of the presence of osteoarthritic signs on radiography at baseline, as defined by a Kellgren and Lawrence score ≥ grade 1.
Main outcome measures Radiological progression of osteoarthritis of the hip, defined as a decrease of joint space width (≥ 1.0 mm) at follow-up or the presence of a total hip replacement.
Methods Potential determinants of progression of hip osteoarthritis were collected at baseline. x Ray films of the hip at baseline and follow-up (mean follow-up time 6.6 years) were evaluated. Multivariate logistic regression models were used to assess the association between potential risk factors and progression of hip osteoarthritis.
Results In 13.1% (1904 subjects) of the study population (mean age 66.2 years), progression of hip osteoarthritis was evident on the radiograph. Starting with a simple model of only directly obtainable variables, the Kellgren and Lawrence score at baseline, when added to the model, was a strong predictor (odds ratio 5.8, 95% confidence interval 4.0 to 8.4), increasing to 24.3 (11.3 to 52.1) in subjects with hip pain at baseline.
Conclusions The Kellgren and Lawrence score at baseline was by far the strongest predictor for progression of hip osteoarthritis, especially in patients with existing hip pain at baseline. In patients with hip pain, a radiograph has strong additional value in identifying those at high risk of progression of hip osteoarthritis.
PMCID: PMC558014  PMID: 15894555
7.  Gender Differences in the Correlation between Symptom and Radiographic Severity in Patients with Knee Osteoarthritis 
The effects of gender on the relationship between symptom manifestations and radiographic grades of knee osteoarthritis are not well understood.
We therefore determined the increments of symptom progression with regard to radiographic grades of knee osteoarthritis and asked if those increments differed by gender and whether symptom severity was differentially manifested by gender within the same grade.
We recruited 660 community residents; 368 (56%) women and 292 (44%) men. The mean subject age was 71.5 years (range, 65–91 years). Severity of symptoms was measured using the WOMAC and SF-36 scales, and the radiographic severity using Kellgren–Lawrence grades. Incremental changes in WOMAC and SF-36 scores were compared between adjacent Kellgren–Lawrence grades separately in men and women, and in the overall population. We compared symptom severity between men and women with the same radiographic grade.
For the entire cohort, the mean incremental change in symptom severity was not gradual between the adjacent radiographic grades but was greater between Kellgren–Lawrence Grades 1 and 2 and Grades 2 and 3 than between Grades 0 and 1 or Grades 3 and 4. The patterns of incremental changes in symptom severity differed between men and women: women had more severe symptom progression between Kellgren–Lawrence Grades 2 and 3 and Grades 3 and 4 than men. Furthermore, women had worse mean WOMAC and SF-36 scores than men with the same radiographic grade of knee osteoarthritis.
These data suggest symptom progression is not gradual between adjacent radiographic grades, and for the same radiographic grade, symptoms are worse in women.
Level of Evidence
Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2881984  PMID: 20204559
8.  Radiographic signs for detection of femoroacetabular impingement and hip dysplasia should be carefully used in patients with osteoarthritis of the hip 
During the last years, terms like acetabular retroversion, excessive overcoverage, and abnormal head-neck-junction with the so called “pistol-grip-deformity” has been added to the classical description of hip dysplasia. These anatomical changes could lead to a femoroacetabular impingement (FAI). Both kinds of FAI has been indentified as a main reason for hip pain and progressive degenerative changes leading to early osteoarthritis of the hip. A lot of radiographic criteria on pelvic views have been established to detect classical dysplasia and FAI. The present study was initiated to assess the hypothesis that age and severity of osteoarthritis affect measurements of different radiographic parameters.
The pelvic radiographs of 1614 patients were measured for head-ratio, CE-angle, roof obliquity, extrusion-index, depth-to-width ratio, CCD-angle, sharp’s angle. To evaluate the severity of osteoarthritis of the hip the classification by Kellgren and Lawrence was used. Associations between age and radiographic parameters or severity of osteoarthritis were assessed by Spearman’s (ρ) or Kendall’s (r) rank correlation coefficient, respectively.
366 (22.7%) patients presented no sign of osteoarthritis, 367 (22.7%) patients presented I° osteoarthritis, 460 (28.5%) patients presented II° osteoarthritis, 307 (19%) III° osteoarthritis and 114 (7.1%) IV° osteoarthritis of the hip. The mean head-ratio of all patients was 1.13 ± 0.26 (0.76 – 2.40), the mean CE-angle 40.05° ± 10.13° (0° - 70°), the mean roof obliquity was 35.27°± 4.96° (10° – 55°), the mean extrusion-index was 12.99 ± 9.21 (6.20 – 95.2), the mean depth-to-width ratio was 59.30 ± 8.90 (6.30 – 100), the mean CCD-angle was 127.68° ± 7.22° (123° – 162°) and the mean sharp’s angle was 9.75° ± 5.40° (1° - 34°) There was a weak association between age and the severity of osteoarthritis of the hips (left: r = 0.291; right: r = 0.275; both P < 0.001) with higher osteoarthritis levels observable for elderly patients).
Severity of osteoarthritis has a negative impact on measurements of different radiographic parameters. Therefore - in our opinion - epidemiological studies on prearthrotic deformities should only be performed in healthy adults with no signs of osteoarthritic changes.
PMCID: PMC4029939  PMID: 24886025
Radiographic Signs; Impingement; Hip; Dysplasia; Osteoarthritis
9.  Vitamin K Deficiency Is Associated with Incident Knee Osteoarthritis 
The American journal of medicine  2013;126(3):243-248.
Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
PMCID: PMC3641753  PMID: 23410565
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
10.  Radiographic knee osteoarthritis in ex-elite table tennis players 
Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.
Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.
The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (P ≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (p = 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (p = 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (p = 0.03).
Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.
PMCID: PMC3327626  PMID: 22309356
11.  Radiographic osteoarthritis of the knee classified by the Ahlbäck and Kellgren & Lawrence systems for the tibiofemoral joint in people aged 35-54 years with chronic knee pain 
Annals of the Rheumatic Diseases  1997;56(8):493-496.
OBJECTIVES—To determine the prevalence of tibiofemoral radiographic knee osteoarthritis (OA) in people aged 35-54 years associated with chronic (> 3 months) knee pain using two different radiographic grading systems.
METHODS—Population based postal survey in a random sample of inhabitants in a district in southern Sweden followed by clinical examination and plain posteroanterior, weight bearing radiographical examination. The Ahlbäck criteria (focusing on joint space narrowing) and the Kell- gren & Lawrence classification for knee OA were used for diagnosing tibiofemoral OA.
RESULTS—A questionnaire was sent to 2000 randomly selected people aged 35-54 years. The response rate was 92.6%. Fifteen per cent of these people reported chronic knee pain. This group (n=279) was offered a clinical and radiographic examination of the knee joint and 204 persons agreed to participate. According to the Kellgren & Lawrence classification 28 subjects had OA of the knee grade 2 or more and 16 grade 3 or more. Radiographically detected OA of the knee according to Ahlbäck was found in 20 cases. The minimum prevalence of radiological tibiofemoral knee OA with knee pain was thus 1.5% for Kellgren & Lawrence grade 2 or more, 0.9% for grade 3 or more, and 1.1% according to the Ahlbäck classification. The agreement between the Kellgren & Lawrence grades 2-3 versus Ahlbäck grade I as well as grade 3-4 versus Ahlbäck grade I-II was good (κ 0.76 and 0.78 respectively).
CONCLUSION—The prevalence of radiographic tibiofemoral OA combined with chronic knee pain in people aged 35-54 years was around 1% as estimated by either the Kellgren & Lawrence or the Ahlbäck classifications systems. Prospective follow up of this cohort should elucidate the significance of knee pain as a sign of developing OA.

PMCID: PMC1752423  PMID: 9306873
12.  Definition of osteoarthritis of the knee for epidemiological studies. 
Annals of the Rheumatic Diseases  1993;52(11):790-794.
OBJECTIVES--There are no agreed criteria for osteoarthritis (OA) of the knee in population studies. The radiographic scoring system of Kellgren and Lawrence has been the system most used in the past and although other methods have been developed, comparisons have not been performed. Therefore these grading systems were compared in radiographs from a general population sample. METHODS--Anteroposterior weightbearing radiographs of 1954 knees from 977 women aged 45-64 years from the Chingford population study were read by a variety of methods, including quantitative measures of minimum joint space, qualitative measures of osteophytes and of joint space, and a qualitative Kellgren and Lawrence global score. All qualitative methods used standardised atlases. Intra-observer and interobserver reproducibility was tested on a subgroup of 100 films using three observers and two readings. Variables were dichotomised at the tenth and second centiles to define OA. Odds ratios were calculated for each method for the association of OA with knee pain, obesity, and with each of the other methods. RESULTS--Most methods had high intraobserver and interobserver reproducibility, except for measurements of lateral joint space. The best predictors of knee pain were the presence of osteophytes and the Kellgren and Lawrence grade. Methods measuring narrowing performed less well, with measurements of lateral joint space being particularly poor. Similar results were achieved in the comparison with obesity and in the comparisons between methods. CONCLUSIONS--These data suggest that the presence or absence of a definite osteophyte read by a single observer with an atlas is the best method of defining OA of the knee for epidemiological studies in women. Assessment of narrowing may be better used in evaluating severity.
PMCID: PMC1005190  PMID: 8250610
13.  Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement 
Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.
This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis.
Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale.
Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.
PMCID: PMC3228720  PMID: 22074728
14.  Prevalence of generalised osteoarthritis in patients with advanced hip and knee osteoarthritis: The Ulm Osteoarthritis Study 
Annals of the Rheumatic Diseases  1998;57(12):717-723.
OBJECTIVES—Different prevalences of generalised osteoarthritis (GOA) in patients with knee and hip OA have been reported. The aim of this investigation was to evaluate radiographic and clinical patterns of disease in a hospital based population of patient subgroups with advanced hip and knee OA and to compare the prevalence of GOA in patients with hip or knee OA, taking potential confounding factors into account.
METHODS—420 patients with hip OA and 389 patients with knee OA scheduled for unilateral total joint replacement in four hospitals underwent radiographic analysis of ipsilateral and contralateral hip or knee joint and both hands in addition to a standardised interview and clinical examination. According to the severity of radiographic changes in the contralateral joints (using Kellgren-Lawrence ⩾ grade 2 as case definition) participants were classified as having either unilateral or bilateral OA. If radiographic changes of two joint groups of the hands (first carpometacarpal joint and proximal/distal interphalangeal joints defined as two separate joint groups) were present, patients were categorised as having GOA.
RESULTS—Patients with hip OA were younger (mean age 60.4 years) and less likely to be female (52.4%) than patients with knee OA (66.3 years and 72.5% respectively). Intensity of pain and functional impairment at hospital admission was similar in both groups, while patients with knee OA had a longer symptom duration (median 10 years) compared with patients with hip OA (5 years). In 41.7% of patients with hip OA and 33.4% of patients with knee OA an underlying pathological condition could be observed in the replaced joint, which allowed a classification as secondary OA. Some 82.1% of patients with hip and 87.4% of patients with knee OA had radiographic changes in their contralateral joints (bilateral disease). The prevalence of GOA increased with age and was higher in female patients. GOA was observed more often in patients with knee OA than in patients with hip OA (34.9% versus 19.3%; OR=2.24; 95% CI: 1.56, 3.21). Adjustment for the different age and sex distribution in both patient groups, however, takes away most of the difference (OR=1.32; 95% CI: 0.89, 1.96).
CONCLUSION—The crude results confirm previous reports as well as the clinical impression of GOA being more prevalent in patients with advanced knee OA than in patients with advanced hip OA. However, these different patterns might be attributed to a large part to a different distribution of age and sex in these hospital based populations.

 Keywords: hip osteoarthritis; knee osteoarthritis; hand osteoarthritis; generalised osteoarthritis
PMCID: PMC1752518  PMID: 10070270
15.  Discordance Between Pain and Radiographic Severity in Knee Osteoarthritis 
Arthritis and rheumatism  2013;65(2):10.1002/art.34646.
Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures.
A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/ Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure–pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1–2 versus 3–4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30).
Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain-sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race.
The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate-to-severe radiographic evidence of pathologic changes of knee OA.
PMCID: PMC3863776  PMID: 22961435
16.  Patellar Skin Surface Temperature by Thermography Reflects Knee Osteoarthritis Severity 
Digital infrared thermal imaging is a means of measuring the heat radiated from the skin surface. Our goal was to develop and assess the reproducibility of serial infrared measurements of the knee and to assess the association of knee temperature by region of interest with radiographic severity of knee Osteoarthritis (rOA).
A total of 30 women (15 Cases with symptomatic knee OA and 15 age-matched Controls without knee pain or knee OA) participated in this study. Infrared imaging was performed with a Meditherm Med2000™ Pro infrared camera. The reproducibility of infrared imaging of the knee was evaluated through determination of intraclass correlation coefficients (ICCs) for temperature measurements from two images performed 6 months apart in Controls whose knee status was not expected to change. The average cutaneous temperature for each of five knee regions of interest was extracted using WinTes software. Knee x-rays were scored for severity of rOA based on the global Kellgren-Lawrence grading scale.
The knee infrared thermal imaging procedure used here demonstrated long-term reproducibility with high ICCs (0.50–0.72 for the various regions of interest) in Controls. Cutaneous temperature of the patella (knee cap) yielded a significant correlation with severity of knee rOA (R = 0.594, P = 0.02).
The skin temperature of the patellar region correlated with x-ray severity of knee OA. This method of infrared knee imaging is reliable and as an objective measure of a sign of inflammation, temperature, indicates an interrelationship of inflammation and structural knee rOA damage.
PMCID: PMC2998980  PMID: 21151853
osteoarthritis; infrared imaging; knee; inflammation; thermography
17.  Radiographic Predictability of Cartilage Damage in Medial Ankle Osteoarthritis 
Radiographic grading has been used to assess and select between treatment options for ankle osteoarthritis. To use radiographic grading systems in clinical practice and scientific studies one must have reliable systems that predict the fate of the cartilage.
We therefore asked whether (1) radiographic grading of ankle osteoarthritis is reliable and (2) grading reflects cartilage damage observed during arthroscopy. We then (3) determined the sensitivity, specificity, and predictive values of the radiographic findings.
Patients and Methods
We examined 74 ankles with medial osteoarthritis and 24 with normal articular cartilage based on arthroscopy. Arthroscopic findings were graded according to the modified Outerbridge grades and all radiographs were graded using the modified Kellgren-Lawrence, Takakura et al., and van Dijk et al. grading systems. The reliability of each radiographic grading system was evaluated. We correlated the radiographic grades and severity of cartilage damage for each radiographic grading system. Sensitivity, specificity, and predictive values of spurs and joint space narrowing with or without talar tilting then were determined.
The interobserver weighted kappa ranged from 0.58 to 0.89 and the intraobserver weighted kappa from 0.51 to 0.85. The correlation coefficients for the Kellgren-Lawrence, Takakura et al., and van Dijk et al. grades were 0.53, 0.42, and 0.42, respectively. Ankles with medial joint space narrowing (Stage 2 of Takakura et al. and van Dijk et al. grades) showed varying severity of cartilage damage. The positive predictive value of cartilage damage increased from 77% for medial joint space narrowing regardless of the presence of talar tilting to 98% for medial joint space narrowing with talar tilting.
Our observations suggest the inclusion of talar tilting in grading schemes enhances the assessment of cartilage damage.
Level of Evidence
Level II, diagnostic study. See the Guidelines for Authors for a complete description of level of evidence.
PMCID: PMC2895860  PMID: 20393817
18.  Arthroscopic partial meniscectomy in middle-aged patients with mild or no knee osteoarthritis: a protocol for a double-blind, randomized sham-controlled multi-centre trial 
Arthroscopic partial meniscectomy has been shown to be of no benefit to patients with concomitant knee osteoarthritis, but the optimal treatment of a degenerative meniscus tear in patients with mild or no knee osteoarthritis is unknown. This article describes the rationale and methodology of a randomized sham-controlled trial to assess the benefit of arthroscopic partial meniscectomy of a medial meniscus tear in patients with mild or no knee osteoarthritis. The objective of the study is to test whether the benefit from arthroscopic partial meniscectomy in patients with knee pain, medial meniscus lesion and mild/no knee osteoarthritis, is greater after arthroscopic partial meniscectomy than following sham surgery.
We will conduct a randomized controlled trial of treatment for degenerative meniscus tears in middle-aged patients (aged 35–55 years) with an MRI-verified medial meniscus lesion and mild or no knee radiographic osteoarthritis (grade 0–2 on the Kellgren & Lawrence scale). Patients will be randomized to receive either conventional arthroscopic partial meniscectomy or a sham surgery procedure. The primary outcome will be the KOOS5 derived from the ‘Knee Injury and Osteoarthritis Outcome Score’ at 2 years follow-up. Secondary outcomes at 2 years will include all five individual subscales of the KOOS, a global perceived effect score, the Short-Form-36 health status score, EQ-5D for economic appraisal and objective tests of muscle strength and physical function. Radiographic knee osteoarthritis will be evaluated at 5 years.
Demonstration of no additional benefit from arthroscopic partial meniscectomy on pain and function should lead to a change in clinical care of patients with a degenerative meniscus tear. The results of this study will provide empirical evidence for the potential benefit/harm of arthroscopic partial meniscectomy compared to a masked sham-therapeutics intervention.
Trial registration
PMCID: PMC3599063  PMID: 23442554
19.  Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study 
For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.
Two sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5° angulation and 15° angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (κ). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.
Observer reproducibility (κ) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (κ 0.73) and foot (κ 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (ptrend <0.001).
The two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.
PMCID: PMC2896354  PMID: 20565825
20.  Associations of vertebral deformities and osteoarthritis with back pain among Japanese women: the Hizen-Oshima study 
Osteoporosis International  2012;24(3):907-915.
We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain.
Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan.
Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren–Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain.
Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5–6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0-–0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1–2.9), independent of other covariates including age and deformities.
Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.
PMCID: PMC3572384  PMID: 22836277
Back pain; Epidemiology; Osteoporosis; Vertebral deformity; Vertebral osteoarthritis
21.  New View on the Initial Development Site and Radiographic Classification System of Osteoarthritis of the Knee Based on Radiographic Analysis 
Radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteophyte at tibial spine (TS), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgren-Lawrence grading system, which is widely used to diagnose OAK, describes narrowing-marginal osteophyte in 4-grades but uses osteophyte at TS only as evidence of OAK without detailed-grading. However, kinematically the knee employs medial TS as an axis while medial and lateral compartments carry the load, suggesting that early OAK would occur sooner at TS than at compartment. Then, Kellgren-Lawrence system may be inadequate to diagnose early-stage OAK manifested as a subtle osteophyte at TS without narrowing-marginal osteophyte. This undiagnosed-OAK will deteriorate becoming a contributing factor in an increasing incidence of OAK.
This study developed a radiographic OAK-marker based on both osteophyte at TS and compartment narrowing-marginal osteophyte and graded as normal, mild, moderate, and severe. With this marker, both knee radiographs of 1,728 patients with knee pain were analyzed.
Among 611 early-stage mild OAK, 562 or 92% started at TS and 49 or 8% at compartment. It suggests the initial development site of OAK, helping develop new site-specific radiographic classification system of OAK accurately to diagnose all severity of OAK at early, intermediate, or late-stage. It showed that Kellgren-Lawrence system missed 92.0% of early-stage mild OAK from diagnosis.
A subtle osteophyte at TS is the earliest radiographic sign of OAK. A new radiographic classification system of OAK was suggested for accurate diagnosis of all OAK in severity and at stage.
PMCID: PMC3615296  PMID: 23675278
axis of the knee; initial development site of knee osteoarthritis; knee kinematics; narrowing of compartment and marginal osteophyte; osteoarthritis of the knee; osteophyte at tibial spine; radiographic classification system of knee osteoarthritis
22.  Radiological progression of osteoarthritis: an 11 year follow up study of the knee. 
Annals of the Rheumatic Diseases  1992;51(10):1107-1110.
A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group.
PMCID: PMC1012413  PMID: 1444622
23.  Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility 
Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals.
In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis.
In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features.
This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.
PMCID: PMC4060235  PMID: 24716474
24.  Osteoarthritis in the elderly: clinical and radiological findings in 79 and 85 year olds. 
Annals of the Rheumatic Diseases  1991;50(8):535-539.
The prevalence of joint complaints and clinical and radiological findings of osteoarthritis in wrist, hand, and knee joints was studied in representative population subsamples of 79 and 85 year olds. Joint complaints, clinical findings of osteoarthritis, and radiographic osteoarthritis were more common in women. Age related differences in the prevalence of osteoarthritis were not found. Although there was a correlation between clinical signs of osteoarthritis and radiographic osteoarthritis, clinical signs were often present without radiographic evidence and moderate and severe radiographic osteoarthritis was often present without clinical signs.
PMCID: PMC1004482  PMID: 1888194
25.  Development of a rapid knee cartilage damage quantification method using magnetic resonance images 
Cartilage morphometry based on magnetic resonance images (MRIs) is an emerging outcome measure for clinical trials among patients with knee osteoarthritis (KOA). However, current methods for cartilage morphometry take many hours per knee and require extensive training on the use of the associated software. In this study we tested the feasibility, reliability, and construct validity of a novel osteoarthritis cartilage damage quantification method (Cartilage Damage Index [CDI]) that utilizes informative locations on knee MRIs.
We selected 102 knee MRIs from the Osteoarthritis Initiative that represented a range of KOA structural severity (Kellgren Lawrence [KL] Grade 0 – 4). We tested the intra- and inter-tester reliability of the CDI and compared the CDI scores against different measures of severity (radiographic joint space narrowing [JSN] grade, KL score, joint space width [JSW]) and static knee alignment, both cross-sectionally and longitudinally.
Determination of the CDI took on average14.4 minutes (s.d. 2.1) per knee pair (baseline and follow-up of one knee). Repeatability was good (intra- and inter-tester reliability: intraclass correlation coefficient >0.86). The mean CDI scores related to all four measures of osteoarthritis severity (JSN grade, KL score, JSW, and knee alignment; all p values < 0.05). Baseline JSN grade and knee alignment also predicted subsequent 24-month longitudinal change in the CDI (p trends <0.05). During 24 months, knees with worsening in JSN or KL grade (i.e. progressors) had greater change in CDI score.
The CDI is a novel knee cartilage quantification method that is rapid, reliable, and has construct validity for assessment of medial tibiofemoral osteoarthritis structural severity and its progression. It has the potential to addresses the barriers inherent to studies requiring assessment of cartilage damage on large numbers of knees, and as a biomarker for knee osteoarthritis progression.
PMCID: PMC4126278  PMID: 25098589
Osteoarthritis; Cartilage; Quantitative measurements; Informative locations; Magnetic resonance imaging

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