Risk factors for symptomatic knee osteoarthritis fifteen to twenty‐two years after meniscectomy

Objective

To evaluate the influence of age, sex, body mass index (BMI), extent of meniscal resection, cartilage status, and knee load on the development of radiographically evident osteoarthritis (OA) of the knee and knee symptoms after meniscal resection.

Methods

We evaluated 317 patients with no cruciate ligament injury (mean ± SD age 54 ± 11 years) who had undergone meniscal resection 15–22 years earlier (followup rate 70%), with radiographic and clinical examination. The Knee injury and Osteoarthritis Outcome Score was used to quantify knee‐related symptoms. Sixty‐eight unoperated subjects identified from national population records were included as a reference group.

Results

Symptomatic radiographic OA (corresponding to Kellgren/Lawrence grade ≥2) was present in 83 of 305 operated knees (27%) and 7 of 68 control knees (10%) (relative risk 2.6, 95% confidence interval [95% CI] 1.3–6.1). Patients who had undergone total meniscectomy and subjects with obesity (BMI ≥30) had a greater likelihood of tibiofemoral radiographic OA than those who had undergone partial meniscal resection and those with a BMI <25, respectively. Furthermore, degenerative meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were associated with radiographic OA more frequently than were longitudinal tear, absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic tibiofemoral or patellofemoral radiographic OA was associated with obesity, female sex, and degenerative meniscal tear.

Conclusion

Contributing risk factors for OA development after meniscal resection are similar to risk factors for common knee OA. Systemic factors and local biomechanical factors interact. Obesity, female sex, and preexisting early‐stage OA are features associated with poor self‐reported and radiographic outcome. Partial meniscal resection is associated with less radiographic OA over time than is total meniscectomy.

     

The association of quadriceps strength with the knee adduction moment in medial knee osteoarthritis

Objective

To investigate the relationship between quadriceps strength and the peak knee adduction moment during walking in medial tibiofemoral osteoarthritis (OA), and whether varus malalignment influences this relationship.

Methods

Maximum isometric quadriceps strength at 60° flexion relative to body mass and the peak knee adduction moment during walking were assessed in 184 community volunteers with medial knee OA. Mechanical knee alignment was determined either directly from full‐leg radiograph or extrapolated from anatomic alignment on knee radiograph using regression equations. Pearson's correlation coefficient was used to assess the association between quadriceps strength and peak knee adduction moment. The independent relationship between quadriceps strength and peak knee adduction moment, and the impact of varus malalignment on this relationship, was assessed using multiple regression analyses with and without adjustment for covariates.

Results

Quadriceps strength was not significantly associated with peak knee adduction moment (r = 0.14, P = 0.059). Neither quadriceps strength (b = 0.25, P = 0.142) nor the interaction between quadriceps strength and varus malalignment (b = ?0.01, P = 0.693) significantly contributed to the variance in peak knee adduction moment. Results were unchanged with the inclusion of covariates.

Conclusion

No significant association was observed between quadriceps strength and the peak knee adduction moment, and the severity of varus malalignment did not influence the relationship. Results suggest that clinicians should not be concerned that patients with knee OA and stronger quadriceps are more likely to demonstrate a higher knee adduction moment.

     

Effect of baseline quadriceps activation on changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis

Objective

To examine whether pretreatment magnitude of quadriceps activation (QA) helps predict changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis (OA). We hypothesized that subjects with lower magnitudes of QA (greater failure of muscle activation) would have smaller gains in strength compared with those with higher magnitudes of QA following exercise therapy.

Methods

One hundred eleven subjects with knee OA (70 women) participated. Baseline measures included demographic information, quadriceps muscle strength, and QA using a burst‐superimposition isometric torque test. Following baseline testing, subjects underwent a 6‐week supervised exercise program designed to improve strength, range of motion, balance and agility, and physical function. On completion of the program, quadriceps strength and QA were reassessed. Multiple regression analysis was used to determine whether baseline QA predicted quadriceps strength scores at the 2‐month followup.

Results

Bivariate correlations demonstrated that baseline QA was significantly associated with quadriceps strength at baseline (ρ = 0.30, P < 0.01) and 2‐month followup (ρ = 0.23, P = 0.01). Greater magnitude of baseline QA correlated with higher strength. While controlling for baseline quadriceps strength and type of exercise therapy, the level of QA did not predict quadriceps strength at the 2‐month followup (β = ?0.04, P = 0.18).

Conclusion

Baseline QA did not predict changes in quadriceps strength following exercise therapy. Measurement of QA using the central activation ratio method does not appear to be helpful in identifying subjects with knee OA who will have difficulty improving quadriceps strength with exercise therapy.

     

Longitudinal performance evaluation and validation of fixed‐flexion radiography of the knee for detection of joint space loss

Objective

The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed‐flexion radiography protocol to detect knee joint space loss over 3 years.

Methods

We assessed the same‐day test–retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23–47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70–79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions.

Results

A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean ± SD joint space loss for all knees over 3 years was 0.24 ± 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean ± SD joint space loss over 3 years was 0.43 ± 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 ± 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup.

Conclusion

Radiography of the knee in the fixed‐flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.

     

Increase in vastus medialis cross‐sectional area is associated with reduced pain,cartilage loss,and joint replacement risk in knee osteoarthritis

Objective

Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross‐sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA).

Methods

One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs).

Results

After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = −0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient −10.9 [95% CI −19.5, −2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient −16.8 [95% CI −28.9, −4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]).

Conclusion

In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

     

Change in joint space width: Hyaline articular cartilage loss or alteration in meniscus?

Objective

To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space.

Methods

The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30‐month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight‐bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0–3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross‐sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables.

Results

We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m²). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space.

Conclusion

The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

     

Association of cartilage defects with loss of knee cartilage in healthy,middle‐age adults: A prospective study

Objective

The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross‐sectionally and longitudinally in healthy, middle‐age adults.

Methods

Eighty‐six healthy men and women (mean ± SD age 53.8 ± 8.8 years) underwent T1‐weighted fat‐suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2‐year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0–4) and as present (a defect score of ≥2) or absent in the medial and lateral tibiofemoral compartments.

Results

Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross‐sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA).

Conclusion

These data suggest that the presence of asymptomatic, non–full‐thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.

     

Knee laxity after staircase exercise predicts radiographic disease progression in medial compartment knee osteoarthritis

Objective

To evaluate whether increased laxity of the knee during daily physical activities such as stair climbing is associated with progression of knee joint osteoarthritis (OA).

Methods

During the years 2001–2003, 136 patients with bilateral primary medial compartment knee joint OA were enrolled in this prospective study. Baseline data collected were body mass index (BMI), muscle power, radiographic joint space width, mechanical axis on standing radiography, and anteroposterior (AP) knee laxity before and after physical exercise. After 8 years of followup, 84 patients were reexamined to assess radiographic changes. Radiographic disease progression was defined as progression of >1 grade on the Kellgren/Lawrence scale.

Results

AP knee laxity increased significantly after stair climbing. Patients with OA progression and those without progression did not differ significantly in age, sex, baseline quadriceps muscle strength, mechanical axis, joint space width, and AP knee laxity before exercise. The 2 groups of patients did, however, differ significantly in baseline BMI and change in AP knee laxity due to exercise. The risk of progression of knee OA increased 4.15‐fold with each millimeter of increase in the change in AP knee laxity due to exercise and 1.24‐fold with each point increase in the BMI.

Conclusion

Our results indicate that patients with OA progression have significantly greater changes in knee joint laxity during physical activities and a higher BMI than patients without OA progression. These findings suggest that larger changes in knee laxity during repetitive physical activities and a higher BMI play significant roles in the progression of knee OA.

     

Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury

Objective

Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known. The purpose of this study was to determine whether genetic loss or pharmacologic inhibition of sclerostin has an impact on knee joint articular cartilage.

Methods

Expression of sclerostin was determined in articular cartilage and bone tissue obtained from mice, rats, and human subjects, including patients with knee osteoarthritis (OA). Mice with genetic knockout (KO) of sclerostin and pharmacologic inhibition of sclerostin with a sclerostin‐neutralizing monoclonal antibody (Scl‐Ab) in aged male rats and ovariectomized (OVX) female rats were used to study the effects of sclerostin on pathologic processes in the knee joint. The rat medial meniscus tear (MMT) model of OA was used to investigate the pharmacologic efficacy of systemic Scl‐Ab or intraarticular (IA) delivery of a sclerostin antibody–Fab (Scl‐Fab) fragment.

Results

Sclerostin expression was detected in rodent and human articular chondrocytes. No difference was observed in the magnitude or distribution of sclerostin expression between normal and OA cartilage or bone. Sclerostin‐KO mice showed no difference in histopathologic features of the knee joint compared to age‐matched wild‐type mice. Pharmacologic treatment of intact aged male rats or OVX female rats with Scl‐Ab had no effect on morphologic characteristics of the articular cartilage. In the rat MMT model, pharmacologic treatment of animals with either systemic Scl‐Ab or IA injection of Scl‐Fab had no effect on lesion development or severity.

Conclusion

Genetic absence of sclerostin does not alter the normal development of age‐dependent OA in mice, and pharmacologic inhibition of sclerostin with Scl‐Ab has no impact on articular cartilage remodeling in rats with posttraumatic OA.

     

Prevalence of magnetic resonance imaging–defined atrophic and hypertrophic phenotypes of knee osteoarthritis in a population‐based cohort

Objective

To describe the association of osteophytes with concomitant cartilage damage, assessed using semiquantitative magnetic resonance imaging (MRI), and to describe the prevalence of atrophic and hypertrophic phenotypes of tibiofemoral knee osteoarthritis (OA) in a population‐based cohort.

Methods

Participants of the Framingham Knee Osteoarthritis Study were examined with a 1.5T MRI system using triplanar intermediate‐weighted fat‐suppressed sequences. Cartilage and osteophytes were assessed using the Whole‐Organ Magnetic Resonance Imaging Score (WORMS). Overall prevalence of knees with severe cartilage damage and concomitant osteophyte status were described. Odds ratios for the likelihood of having severe cartilage damage according to osteophyte size were estimated using a logistic regression model. An additional analysis assessed knees according to phenotype in relation to radiographic OA status, with the atrophic phenotype being defined as knees with absent or only tiny osteophytes (WORMS grade ≤2 on a 0–7 scale) in all 10 tibiofemoral subregions but exhibiting severe cartilage damage, and the hypertrophic phenotype being defined as knees with large osteophytes (WORMS grade ≥5 on a 0–7 scale) but lacking substantial cartilage damage.

Results

In this study, 1,597 knees of 1,248 subjects were included. Of the 67 knees with large osteophytes, 54 (80.6%) exhibited severe cartilage damage. The risk of severe cartilage damage increased markedly with increasing osteophyte size. Twenty‐one knees (1.3%) showed an atrophic phenotype. Only 3 knees (0.2%) exhibited a hypertrophic phenotype.

Conclusion

The majority of knees with severe tibiofemoral cartilage damage exhibited moderate to large osteophytes. The larger the osteophyte, the more likely was the presence of severe cartilage damage. A minority of knees exhibited the atrophic phenotype, which also included knees without radiographic OA. The hypertrophic phenotype was extremely rare.

     

Serum levels of vitamin D,sunlight exposure,and knee cartilage loss in older adults: The Tasmanian older adult cohort study

Objective

To determine the associations between serum levels of vitamin D, sunlight exposure, and knee cartilage loss cross‐sectionally and longitudinally in older adults.

Methods

A total of 880 randomly selected subjects (mean age 61 years [range 51–79 years], 50% women) were studied at baseline, and 353 of these subjects were studied 2.9 years later. Serum levels of 25‐hydroxyvitamin D (25[OH]D) were assessed by radioimmunoassay, and sunlight exposure was assessed by questionnaire. T1‐weighted fat‐suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine knee cartilage volume and defects. Knee radiographic osteoarthritis (OA) and knee pain were also assessed.

Results

The mean 25(OH)D serum level was 52.8 nmoles/liter at baseline (range 13–119 nmoles/liter). Winter sunlight exposure and serum 25(OH)D level were both positively associated with medial and lateral tibial cartilage volume, and a serum 25(OH)D level <50 nmoles/liter was associated with increased medial tibiofemoral joint space narrowing (all P < 0.05). Longitudinally, baseline serum 25(OH)D level predicted change in both medial and lateral tibial cartilage volume (β = +0.04% per annum per nmole/liter for both; P < 0.05), and change in serum 25(OH)D level was positively associated with change in medial tibial cartilage volume. These associations were consistent in subjects with radiographic OA and knee pain and/or in women, but not in men or in subjects without radiographic OA or knee pain.

Conclusion

Sunlight exposure and serum 25(OH)D levels are both associated with decreased knee cartilage loss (assessed by radiograph or MRI). This is best observed using the whole range of 25(OH)D levels rather than predefined cut points and implies that achieving vitamin D sufficiency may prevent and/or retard cartilage loss in knee OA.

     

Longitudinal effect of vigorous physical activity on patella cartilage morphology in people without clinical knee disease

Objective

There are few data concerning possible long‐term effects of physical activity on cartilage change in the patellofemoral compartment. We examined the effect of participation in vigorous physical activity on changes to patella cartilage over 2 years.

Methods

A total of 297 healthy adults ages 50–79 years with no history of knee injury or symptoms were recruited from an existing study. Physical activity data were obtained by questionnaire at baseline (2003–2004). Patella cartilage volume and defects were determined by magnetic resonance imaging at baseline (2003–2004) and followup (2006–2007).

Results

Participation in vigorous physical activity at baseline was associated with a reduced rate of patella cartilage volume loss (?21.2 mm³ per annum [95% confidence interval (95% CI) ?41.5, ?1.0; P = 0.04]) and a trend toward less risk of worsening patella cartilage defects (odds ratio 0.4; 95% CI 0.2, 1.1 [P = 0.07]) over the subsequent 2 years. In the subgroup with no significant patella cartilage defects at baseline (n = 192), participation in vigorous physical activity was associated with a reduced annual rate of patella cartilage volume loss (95% CI ?53.8, ?7.8; P = 0.03) and a trend for fewer new patella cartilage defects (95% CI 0.1, 1.1; P = 0.08). No significant relationships were found between vigorous physical activity and cartilage volume change or defect progression in the subgroup with prevalent patella cartilage defects at baseline.

Conclusion

These observations suggest that vigorous physical activity is beneficial to patellofemoral joints for people without preexisting cartilage damage. Weight‐bearing vigorous physical activity might, therefore, be useful in the prevention of patellofemoral osteoarthritis.

     

Magnetic resonance imaging–based assessment of cartilage loss in severe osteoarthritis: Accuracy,precision, and diagnostic value

Objective

To examine the in vivo accuracy and precision of magnetic resonance imaging (MRI)–based assessment of cartilage loss in patients with severe osteoarthritis (OA) of the knee.

Methods

High‐resolution MRI images of the tibial cartilage were obtained in 8 patients prior to total knee arthroplasty, using a water‐excitation gradient‐echo MRI sequence (acquisition time 6 minutes 19 seconds; spatial resolution 1.2 × 0.31 × 0.31 mm³). The MRI measurements were repeated after joint repositioning. The precision of the cartilage volume and thickness computations was determined after 3dimensional reconstruction. During surgery, the tibial plateaus were resected, and the MRI data were compared with water displacement of surgically retrieved cartilage.

Results

The standard deviation (coefficient of variation) of repeated tibial cartilage volume measurements was 56 mm³ (5.5%) medially and 59 mm³ (3.8%) laterally. The deviation from surgically removed tissue was −13%, on average, with a high linear correlation between both methods (r = 0.98). In patients with varus OA, the tissue loss was estimated to be 1,290 mm³ in the medial tibia and 1,150 mm³ in the lateral tibia, compared with the data in healthy volunteers.

Conclusion

Noninvasive quantitative MRI‐based analysis of cartilage morphometry in severe OA is accurate, precise, and displays high potential diagnostic value.

     

Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle‐aged and elderly persons: The multicenter osteoarthritis study

Objective

Although partial meniscectomy is a risk factor for the development of knee osteoarthritis (OA), there is a lack of evidence that meniscal damage that is not treated with surgery would also lead to OA, suggesting that surgery itself may cause joint damage. Furthermore, meniscal damage is common. The aim of this study was to evaluate the association between meniscal damage in knees without surgery and the development of radiographic tibiofemoral OA.

Methods

We conducted a prospective case–control study nested within the observational Multicenter Osteoarthritis Study, which included a sample of men and women ages 50–79 years at high risk of knee OA who were recruited from the community. Patients who had no baseline radiographic knee OA but in whom tibiofemoral OA developed during the 30‐month followup period were cases (n = 121). Control subjects (n = 294) were drawn randomly from the same source population as cases but had no knee OA after 30 months of followup. Individuals whose knees had previously undergone surgery were excluded. Meniscal damage was defined as the presence of any medial or lateral meniscal tearing, maceration, or destruction.

Results

Meniscal damage at baseline was more common in case knees than in control knees (54% versus 18%; P < 0.001). The model comparing any meniscal damage with no meniscal damage (adjusted for baseline age, sex, body mass index, physical activity, and mechanical knee alignment) yielded an odds ratio of 5.7 (95% confidence interval 3.4–9.4).

Conclusion

In knees without surgery, meniscal damage is a potent risk factor for the development of radiographic OA. These results highlight the need for better understanding, prevention, and treatment of meniscal damage.

     

Varus–valgus alignment: Reduced risk of subsequent cartilage loss in the less loaded compartment

Objective

Varus–valgus alignment has been linked to subsequent progression of osteoarthritis (OA) within the mechanically stressed (medial for varus, lateral for valgus) tibiofemoral compartment. Cartilage data from the off‐loaded compartment are sparse. The purpose of this study was to examine our hypotheses that neutral and valgus (versus varus) knees each have reduced odds of cartilage loss in the medial subregions and that neutral and varus (versus valgus) knees each have reduced odds of cartilage loss in the lateral subregions.

Methods

Patients with knee OA underwent knee magnetic resonance imaging at baseline and 2 years. The mean cartilage thickness was quantified within 5 tibial and 3 femoral subregions. We used logistic regression with generalized estimating equations to analyze the relationship between baseline alignment and subregional cartilage loss at 2 years, adjusting for age, sex, body mass index, and disease severity.

Results

A reduced risk of cartilage loss in the medial subregions was associated with neutral (versus varus) alignment (external tibial, central femoral, external femoral) and with valgus (versus varus) alignment (central tibial, external tibial, central femoral, external femoral). A reduced risk of cartilage loss in the lateral subregions was associated with neutral (versus valgus) alignment (central tibial, internal tibial, posterior tibial) and with varus (versus valgus) alignment (central tibial, external tibial, posterior tibial, external femoral).

Conclusion

Neutral and valgus alignment were each associated with a reduction in the risk of subsequent cartilage loss in certain medial subregions and neutral and varus alignment with a reduction in the risk of cartilage loss in certain lateral subregions. These results support load redistribution as an in vivo mechanism of the long‐term alignment effects on cartilage loss in knee OA.

     

Antiinflammatory and chondroprotective effects of intraarticular injection of adipose‐derived stem cells in experimental osteoarthritis

Objective

In experimental collagenase‐induced osteoarthritis (OA) in the mouse, synovial lining macrophages are crucial in mediating joint destruction. It was recently shown that adipose‐derived stem cells (ASCs) express immunosuppressive characteristics. This study was undertaken to explore the effect of intraarticular injection of ASCs on synovial lining thickness and its relation to joint pathology in experimental mouse OA.

Methods

ASCs were isolated from fat surrounding the inguinal lymph nodes and cultured for 2 weeks. Experimental OA was induced by injection of collagenase into the knee joints of C57BL/6 mice. OA phenotypes were measured within 8 weeks after induction. Histologic analysis was performed, and synovial thickening, enthesophyte formation, and cartilage destruction were measured in the knee joint.

Results

ASCs were injected into the knee joints of mice 7 days after the induction of collagenase‐induced OA. On day 1, green fluorescent protein–labeled ASCs were attached to the lining layer in close contact with macrophages. Thickening of the synovial lining, formation of enthesophytes associated with medial collateral ligaments, and formation of enthesophytes associated with cruciate ligaments were significantly inhibited on day 42 after ASC treatment, by 31%, 89%, and 44%, respectively. Destruction of cartilage was inhibited on day 14 (65%) and day 42 (35%). In contrast to early treatment, injection of ASCs on day 14 after OA induction showed no significant effect on synovial activation or joint pathology on day 42.

Conclusion

These findings indicate that a single injection of ASCs into the knee joints of mice with early‐stage collagenase‐induced OA inhibits synovial thickening, formation of enthesophytes associated with ligaments, and cartilage destruction.

     

Impact of type of meniscal tear on radiographic and symptomatic knee osteoarthritis: A sixteen‐year followup of meniscectomy with matched controls

Objective

To investigate long‐term radiographic and patient‐relevant outcome of isolated limited meniscectomy with regard to type of meniscal tear and extent of surgical resection.

Methods

We studied 155 patients with intact cruciate ligaments (mean ± SD age 54 ± 12 years) who had undergone meniscectomy an average of 16 ± 1 years earlier. The patients were examined using standardized radiography and validated self‐administered questionnaires. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to quantify knee‐related symptoms, and the definition of a symptomatic knee was determined. We used 68 control subjects matched for age, sex, and body mass index to calculate the relative risks (RRs).

Results

Radiographic tibiofemoral osteoarthritis (OA) (Kellgren/Lawrence grade ≥2) was present in 66 index knees (43%), of which 39 (59%) were considered to be symptomatic according to the KOOS. In total, 77 patients (50%) had a symptomatic index knee. In a multivariate model, degenerative meniscal tears were associated with both radiographic OA (P = 0.030) and combined radiographic and symptomatic OA (P ≤ 0.015). The RRs for combined radiographic and symptomatic OA after degenerative and traumatic types of meniscal tear were 7.0 (95% confidence interval [95% CI] 2.1–23.5) and 2.7 (95% CI 0.9–7.7), respectively, compared with matched controls.

Conclusion

An isolated meniscal tear treated by limited meniscectomy is associated with a high risk of radiographic and symptomatic tibiofemoral OA at 16‐year followup. Factors associated with worse outcome were degenerative meniscal lesions and extensive resections. We suggest that degenerative meniscal tears may be associated with incipient OA, and that the meniscal tear signals the first symptom of the disease.

     

Effects of doxycycline on progression of osteoarthritis: Results of a randomized,placebo‐controlled,double‐blind trial

Objective

To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.

Methods

In this placebo‐controlled trial, obese women (n = 431) ages 45–64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6‐month intervals.

Results

Seventy‐one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ± SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ± 0.42 mm versus 0.24 ± 0.54 mm); after 30 months, it was 33% less (0.30 ± 0.60 mm versus 0.45 ± 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a ≥20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a ≥20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.

Conclusion

Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

     

Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the Osteoarthritis Initiative

Objective

To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end‐stage radiographic OA.

Methods

One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight‐bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status.

Results

Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (<1%; minimal SRM ?0.22) and not significantly different from healthy knees. Knees with calculated K/L grade 3 showed substantial loss of cartilage thickness (up to ?2.5%; minimal SRM ?0.35), with OV1 changes being significantly (P < 0.05) greater than those in healthy knees. Calculated K/L grade 4 knees displayed the largest rate of loss across radiographic OA grades (up to ?3.9%; minimal SRM ?0.51), with OV1 changes also significantly (P < 0.05) greater than in healthy knees.

Conclusion

MRI‐based cartilage thickness showed high rates of loss in knees with moderate and end‐stage radiographic OA, and small rates (indistinguishable from healthy knees) in mild radiographic OA. From the perspective of sensitivity to change, end‐stage radiographic OA knees need not be excluded from longitudinal studies using MRI cartilage morphology as an end point.