No degeneration found in focal cartilage defects evaluated with dGEMRIC at 12-year follow-up

Background and purpose — The natural history of focal cartilage defects (FCDs) is still unresolved, as is the long-term cartilage quality after cartilage surgery. It has been suggested that delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a biomarker of early OA. We aimed to quantitatively evaluate the articular cartilage in knees with FCDs, 12 years after arthroscopic diagnosis.

Patients and methods — We included 21 patients from a cohort of patients with knee pain who underwent arthroscopy in 1999. Patients with a full-thickness cartilage defect, stable knees, and at least 50% of both their menisci intact at baseline were eligible. 10 patients had cartilage repair performed at baseline (microfracture or autologous chondrocyte implantation), whereas 11 patients had either no additional surgery or simple debridement performed. Mean follow-up time was 12 (10–13) years. The morphology and biochemical features were evaluated with dGEMRIC and T2 mapping. Standing radiographs for Kellgren and Lawrence (K&L) classification of osteoarthritis (OA) were obtained. Knee function was assessed with VAS, Tegner, Lysholm, and KOOS.

Results — The dGEMRIC showed varying results but, overall, no increased degeneration of the injured knees. Degenerative changes (K&L above 0) were, however, evident in 13 of the 21 knees.

Interpretation — The natural history of untreated FCDs shows large dGEMRIC variations, as does the knee articular cartilage of surgically treated patients. In this study, radiographic OA changes did not correlate with cartilage quality, as assessed with dGEMRIC.     

How Does the dGEMRIC Index Change After Surgical Treatment for FAI? A Prospective Controlled Study: Preliminary Results

Background

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) allows an objective, noninvasive, and longitudinal quantification of biochemical cartilage properties. Although dGEMRIC has been used to monitor the course of cartilage degeneration after periacetabular osteotomy (PAO) for correction of hip dysplasia, such longitudinal data are currently lacking for femoroacetabular impingement (FAI).

Questions/purposes

(1) How does the mean acetabular and femoral dGEMRIC index change after surgery for FAI at 1-year followup compared with a similar group of patients with FAI treated without surgery? (2) Does the regional distribution of the acetabular and femoral dGEMRIC index change for the two groups over time? (3) Is there a correlation between the baseline dGEMRIC index and the change of patient-reported outcome measures (PROMs) at 1-year followup? (4) Among those treated surgically, can dGEMRIC indices distinguish between intact and degenerated cartilage?

Methods

We performed a prospective, comparative, nonrandomized, longitudinal study. At the time of enrollment, the patients’ decision whether to undergo surgery or choose nonoperative treatment was not made yet. Thirty-nine patients (40 hips) who underwent either joint-preserving surgery for FAI (20 hips) or nonoperative treatment (20 hips) were included. The two groups did not differ regarding Tönnis osteoarthritis score, preoperative PROMs, or baseline dGEMRIC indices. There were more women (60% versus 30%, p = 0.003) in the nonoperative group and patients were older (36 ± 8 years versus 30 ± 8 years, p = 0.026) and had lower alpha angles (65° ± 10° versus 73° ± 12°, p = 0.022) compared with the operative group. We used a 3.0-T scanner and a three-dimensional dual flip-angle gradient-echo technique for the dGEMRIC technique for the baseline and the 1-year followup measurements. dGEMRIC indices of femoral and acetabular cartilage were measured separately on the initial and followup radial dGEMRIC reformats in direct comparison with morphologic radial images. Regions of interest were placed manually peripherally and centrally within the cartilage based on anatomic landmarks at the clockface positions. The WOMAC, the Hip disability and Osteoarthritis Outcome Score, and the modified Harris hip score were used as PROMs. Among those treated surgically, the intraoperative damage according to the Beck grading was recorded and compared with the baseline dGEMRIC indices.

Results

Although both the operative and the nonoperative groups experienced decreased dGEMRIC indices, the declines were more pronounced in the operative group (−96 ± 112 ms versus −16 ± 101 ms on the acetabular side and −96 ± 123 ms versus −21 ± 83 ms on the femoral side in the operative and nonoperative groups, respectively; p < 0.001 for both). Patients undergoing hip arthroscopy and surgical hip dislocation experienced decreased dGEMRIC indices; the decline in femoral dGEMRIC indices was more pronounced in hips after surgical hip dislocation (−120 ± 137 ms versus −61 ± 89 ms, p = 0.002). In the operative group a decline in dGEMRIC indices was observed in 43 of 44 regions over time. In the nonoperative group a decline in dGEMRIC indices was observed in four of 44 regions over time. The strongest correlation among patients treated surgically was found between the change in WOMAC and baseline dGEMRIC indices for the entire joint (R = 0.788, p < 0.001). Among those treated nonoperatively, no correlation between baseline dGEMRIC indices and change in PROMs was found. In the posterosuperior quadrant, the dGEMRIC index was higher for patients with intact cartilage compared with hips with chondral lesions (592 ± 203 ms versus 444 ± 205 ms, p < 0.001).

Conclusions

We found a decline in acetabular, femoral, and regional dGEMRIC indices for the surgically treated group at 1-year followup despite an improvement in all PROMs. We observed a similar but less pronounced decrease in the dGEMRIC index in symptomatic patients without surgical treatment indicating continuous cartilage degeneration. Although treatment of FAI is intended to alter the forces acting across the hip by eliminating impingement, its effects on cartilage biology are not clear. dGEMRIC provides a noninvasive method of assessing these effects. Longer term studies will be needed to determine whether the matrix changes of the bradytrophic cartilage seen here are permanent or clinically important.

Level of Evidence

Level II, therapeutic study.

     

Early osteoarthritis after slipped capital femoral epiphysis

Background and purpose — Slipped capital femoral epiphysis (SCFE) results in a more or less pronounced deformity of the proximal femur, sometimes causing impingement and early osteoarthritis. We studied early osteoarthritis after SCFE and the association with deformity and self-reported hip function, pain, and quality of life.

Patients and methods — 9 women and 16 men, mean age 32 (21–50) years, 19 with unilateral and 6 with bilateral SCFE, participated. All patients had primarily been operated by pin or screw with no attempt at reposition of the slip. Hips were examined by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), which quantifies and locates cartilage degeneration. Plain radiographs were used to measure deformity as determined by the alpha angle. Outcome was assessed by Oxford hip score, Hip Groin Outcome score and EQ-5D-Visual scale.

Results — In the 19 unilateral SCFE, on the slip side dGEMRIC mean value was 533?ms (SD 112, range 357–649) versus mean 589?ms (SD 125, range 320–788) on the non-slip side, (p = 0.01). The dGEMRIC correlated negatively to the alpha angle, correlation coefficient (CC) = –0.60, (p = 0.002). Oxford hip score, pain, and EQ-5D-Visual scale correlated to dGEMRIC CC =0.43 (p = 0.03), CC =0.40 (p = 0.05), and CC =0.49 (p = 0.01) respectively.

Interpretation — After SCFE, even relatively mild residual hip deformity can be associated with cartilage degeneration. A high alpha angle was associated with worse cartilage status. The Oxford hip score identified symptoms even though our patients had not previously sought medical care after the index operation. Quality of life showed strong inverse correlation with cartilage degeneration. Objective assessment of early cartilage degeneration may be useful for treatment decisions and follow-up.     

dGEMRIC as a function of BMI

OBJECTIVE: Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) reflects cartilage glycosaminoglycan (GAG) distribution. The technique assumes that the plasma levels of the contrast agent Gd-DTPA(2-) are the same across individuals after intravenous (IV) injection, when dosing by weight. However, adipose tissue has lower extracellular water (ECW) than lean tissue. The aims of this study were to measure (1) plasma Gd-DTPA(2-) levels vs body mass index (BMI), and (2) dGEMRIC vs BMI after correcting for the dose-BMI effect. METHOD: (1) Plasma Gd-DTPA(2-) levels were analyzed at 3-90 min after IV injection per body weight in 24 individuals with BMI between 21.5 and 46.5. (2) dGEMRIC was compared with BMI in 19 asymptomatic volunteers and 23 with osteoarthritis (OA). RESULTS: (1) Plasma Gd-DTPA(2-) kinetics were similar in obese and non-obese groups, however, overall concentration was higher in the obese group. A very obese subject (BMI 45) would have 1.4 times higher Gd-DTPA(2-) concentration than a lean subject (BMI 20), which translates into a bias in dGEMRIC of up to 20%. (2) With dose bias taken into account, dGEMRIC showed no correlation with BMI in asymptomatic knees. In OA knees, unnarrowed femoral compartments demonstrated a negative correlation between dGEMRIC and BMI (R=0.57, P=0.004). No correlation was seen in radiographically narrowed compartments. CONCLUSION: BMI can be a source of dosing bias in dGEMRIC and a correction factor should be considered in cross-sectional studies with a large range of BMI. There is no correlation between dGEMRIC and BMI in asymptomatic knees, but a negative correlation in OA knees.     

Both 3-T dGEMRIC and Acetabular-Femoral T2 Difference May Detect Cartilage Damage at the Chondrolabral Junction

Background

In addition to case reports of gadolinium-related toxicities, there are increasing theoretical concerns about the use of gadolinium for MR imaging. As a result, there is increasing interest in noncontrast imaging techniques for biochemical cartilage assessment. Among them, T2 mapping holds promise because of its simplicity, but its biophysical interpretation has been controversial.

Questions/purposes

We sought to determine whether (1) 3-T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping are both capable of detecting cartilage damage at the chondrolabral junction in patients with femoroacetabular impingement (FAI); and (2) whether there is a correlation between these two techniques for acetabular and femoral head cartilage assessment.

Methods

Thirty-one patients with hip-related symptoms resulting from FAI underwent a preoperative 3-T MRI of their hip that included dGEMRIC and T2 mapping (symptomatic group, 16 women, 15 men; mean age, 27 ± 8 years). Ten volunteers with no symptoms according to the WOMAC served as a control (asymptomatic group, seven women, three men; mean age, 28 ± 3 years). After morphologic cartilage assessment, acetabular and femoral head cartilages were graded according to the modified Outerbridge grading criteria. In the midsagittal plane, single-observer analyses of precontrast T1 values (volunteers), the dGEMRIC index (T1_Gd, patients), and T2 mapping values (everyone) were compared in acetabular and corresponding femoral head cartilage at the chondrolabral junction of each hip by region-of-interest analysis.

Results

In the symptomatic group, T1_Gd and T2 values were lower in the acetabular cartilage compared with corresponding femoral head cartilage (T1_Gd: 515 ± 165 ms versus 650 ± 191 ms, p < 0.001; T2: 39 ± 8 ms versus 46 ± 10 ms, p < 0.001). In contrast, the asymptomatic group demonstrated no differences in T1 and T2 values for the acetabular and femoral cartilages with the numbers available (T1: 861 ± 130 ms versus 860 ± 182 ms, p = 0.98; T2: 43 ± 7 ms versus 42 ± 6 ms, p = 0.73). No correlation with the numbers available was noted between the modified Outerbridge grade and T1, T1_Gd, or T2 as well as between T2 and either T1 or T1_Gd.

Conclusions

Without the need for contrast media application, T2 mapping may be a viable alternative to dGEMRIC when assessing hip cartilage at the chondrolabral junction. However, acquisition-related phenomena as well as regional variations in the microstructure of hip cartilage necessitate an internal femoral head cartilage control when interpreting these results.

Level of Evidence

Level IV, diagnostic study.

     

Structural abnormalities detected by knee magnetic resonance imaging are common in middle-aged subjects with and without risk factors for osteoarthritis

Background and purpose — Few data are available regarding structural changes present in knees without radiographically evident osteoarthritis (OA). We evaluated the prevalence of findings suggestive of knee OA by magnetic resonance imaging (MRI) in middle-aged subjects without radiographic OA with or without OA risk factors.

Patients and methods — 340 subjects from the Osteoarthritis Initiative, aged 45–55 years (51% women) with Kellgren–Lawrence grade 0 in both knees, who had 3T knee MR images were eligible. 294 subjects had risk factors and 46 were without risk factors. MR images were assessed using the MOAKS scoring system.

Results — At least 1 MR-detected feature was found in 96% (283/294) of subjects with risk factors and in 87% (40/46) of those without. Cartilage damage (82%), bone marrow lesions (60%), osteophytes (45%), meniscal body extrusion (32%), and synovitis–effusion (29%) were the most common findings in subjects with risk factors, while cartilage damage (67%), osteophytes (46%), meniscal body extrusion (37%), and bone marrow lesions (35%) were most common in subjects without. The prevalence of any abnormality was higher in subjects with OA risk factors than in subjects without (prevalence ratio adjusted for age and sex 1.3 [95% CI 1.1–1.6]), so was prevalence of subchondral cysts and bone marrow lesions. MR-detected structural changes were more frequent in patellofemoral joints.

Interpretation — Our findings highlight the great challenge in distinguishing pathological features of early knee OA from what could be considered part of “normal ageing.” Bone marrow lesions were more frequently found in subjects with multiple OA risk factors.     

Articular cartilage of the knee 3 years after ACL reconstruction: A quantitative T2 relaxometry analysis of 10 knees

Background and purpose

T1ρ or T2 relaxation imaging has been increasingly used to evaluate the cartilage of the knee. We investigated the cartilage of ACL-reconstructed knees 3 years after surgery using T2 relaxation times.

Patients and methods

10 patients with a clinically successful unilateral ACL reconstruction were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images of both knees were acquired using a 3T MRI scanner for T2 mapping of the tibiofemoral cartilage. T2 values of the superficial and deep zones of the tibiofemoral cartilage were analyzed in sub-compartmental areas and compared between the ACL-reconstructed and uninjured contralateral knees.

Results

Higher T2 values were observed in 1 or more sub-compartmental areas of each ACL-reconstructed knee compared to the uninjured contralateral side. Most of the T2 increases were observed at the superficial zones of the cartilage, especially at the medial compartment. At the medial compartment of the ACL-reconstructed knee, the T2 values of the femoral and tibial cartilage were increased by 3–81% compared to the uninjured contralateral side, at the superficial zones of the weight-bearing areas. T2 values in the superficial zone of the central medial femoral condyle differed between the 2 groups (p = 0.002).

Interpretation

The articular cartilage of ACL-reconstructed knees, although clinically satisfactory, had higher T2 values in the superficial zone of the central medial femoral condyle than in the uninjured contralateral side 3 years after surgery. Further studies are warranted to determine whether these patients would undergo cartilage degeneration over time.ACL reconstruction is widely used to restore stability of the knee after ACL injury. However, after 10–15 years of follow-up, osteoarthritis (OA) has been reported in 15–85% of patients (Ajuied et al. 2013, Chalmers et al. 2014). Radiographic features of OA appear only after substantial deterioration has occurred, and several years—or even decades—probably separate the first molecular changes from overt radiographic changes. Considerable progress has been made in explaining these early molecular changes by detecting alterations in the biochemical composition of the cartilage using MRI biomarkers such as T1ρ, T2, dGEMRIC, and sodium MRI (Choi and Gold 2011). These studies indicated that MR measurements of biomarkers might be an efficient tool for detection of changes in the biochemical composition of articular cartilage.Recently, some studies have used biochemical MRI methods to investigate the matrix changes in articular cartilage following ACL reconstruction, and early changes in the biochemical composition of articular cartilage in ACL-reconstructed knees have been investigated in relation to healthy populations or uninjured contralateral knees (Li et al. 2011, Haughom et al. 2012, Hirose et al. 2013, Su et al. 2013, Van Ginckel et al. 2013, Theologis et al. 2014). As progression of cartilage degeneration can be a long-term process, data on changes in the biochemical properties of cartilage at different postoperative times and in different patient populations are necessary for quantitative evaluation of cartilage degeneration after the surgery. We therefore conducted this study to evaluate the biochemical status of articular cartilage in ACL-reconstructed knees using T2 relaxation times (T2 values) at 3-year follow-up. The uninjured, healthy contralateral knees were used as a control, to eliminate inter-subject variation. The working hypothesis was that the cartilage in ACL-reconstructed knees would have higher T2 values than cartilage in uninjured contralateral knees 3 years after surgery.     

Value of delayed gadolinium‐enhanced magnetic resonance imaging of cartilage for the pre‐operative assessment of cervical intervertebral discs

The study was performed to preoperatively assess the cartilage integrity of cervical intervertebral discs (IVDs) using Delayed Gadolinium‐Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC). Therefore, 53 cervical intervertebral discs of nine preoperative patients with neck and shoulder/arm pain scheduled for discectomy (five females, four males; mean age: 47.1 ± 8.4 years; range: 36–58 years) were included for biochemical analysis in this retrospective study. The patients underwent 3T magnetic resonance imaging (MRI) including biochemical imaging with dGEMRIC and morphological, sagittal T2 weighted (T2w) imaging. Cervical IVDs were rated using an MRI based grading system for cervical IVDs on T2w images. Region‐of‐interest measurements were performed in the nucleus pulposus (NP) and annulus fibrosus (AF) and a dGEMRIC index was calculated. Our results demonstrated that IVDs scheduled for discectomy showed significantly lower dGEMRIC index compared to IVDs that did not require surgical intervention in NP and AF (NP: 898.4 ± 191.9 ms vs. 1,150.3 ± 320.7 ms, p = 0.008; AF: 738.7 ± 183.8 ms vs. 984.6 ± 178.9 ms, p = 0.008). For Miyazaki score 3, the dGEMRIC indices were significantly lower in IVDs scheduled for surgery compared to non‐operated discs for NP (p = 0.043) and AF (p = 0.018). In conclusion we could demonstrate that biochemical imaging with dGEMRIC is feasible in cervical IVDs. Significantly lower dGEMRIC index suggested GAG depletion in degenerated cervical IVD, scheduled for discectomy. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1824–1830, 2017.

     

Longitudinal evaluation of cartilage after osteochondral autogenous transfer with delayed gadolinium‐enhanced MRI of the cartilage (dGEMRIC)

The aim was to use repeat delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC) to estimate glycosaminoglycan (GAG) content in reparative cartilage after osteochondral autogenous transfer (OAT). The study group comprised 7 knees of 7 patients that were examined three times by dGEMRIC, at 3, 6, and 12 months using a 1.5 Tesla MRI system in both OAT operated and nonoperated condyles at 90 min after the injection. The gadolinium diethylene triamine pentaacetic acid (Gd‐DTPA)^2? containing contrast medium (0.2 mmols/kg) was injected intravenously. The mean T1 values of the plug cartilage at 3, 6, and 12 months after OAT was 230 ± 40, 213 ± 31, and 230 ± 23 ms (mean ± SD), respectively. There were differences between the plug and control cartilage at 3 (p < 0.01) and 12 (p < 0.05) months after OAT, but not at 6 months (p = 0.089). No T1 changes were detected between the plug cartilage at the different time points after OAT. The fact that the GAG content of the OAT plugs were maintained for 12‐month study period suggest that no major deterioration of load‐bearing properties occurs in the cartilage after the OAT. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:221–225, 2012     

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration.MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%).ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration.ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.     

Evaluation of cartilage repair in the distal femur after autologous chondrocyte transplantation using T2 relaxation time and dGEMRIC

OBJECTIVES: To investigate the potential of combining T2 relaxation time and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) measurements after autologous chondrocyte transplantation (ACT). MATERIALS AND METHODS: T2 and dGEMRIC maps were measured in the sagittal and coronal directions in 12 patients 10-15 months after ACT surgery. Grafts were assessed for bulk full thickness, superficial and deep tissue T2 and dGEMRIC values, and were compared to control cartilage. RESULTS: All ACT grafts showed filling of the repair area to the level of or above the articular surface. Matrix of the grafts lacked the classical laminar structure and appeared more heterogenous on T2 maps than control cartilage. As compared to control cartilage, ACT grafts showed significantly longer T2 values for bulk tissue as well as for the superficial 50% and deep 50% of tissue except for superficial cartilage in the coronal direction. dGEMRIC assessment in the sagittal and coronal directions did not show a significant difference between bulk, superficial or deep tissue as compared to the control cartilage. Superficial and deep ACT tissue did not differ statistically in terms of their T2 or dGEMRIC values. CONCLUSIONS: These preliminary results suggest that, according to T2 measurements, ACT repair tissue at 10-15 months differs from normal cartilage and probably lacks the preferential collagen arrangement of normal cartilage, while according to dGEMRIC a varying degree of proteoglycan replenishment takes place. Combining these two quantitative magnetic resonance imaging techniques enables a more comprehensive characterization of cartilage repair than before.     

Signs of knee osteoarthritis common in 620 patients undergoing arthroscopic surgery for meniscal tear

Background and purpose — Recent evidence has questioned the effect of arthroscopic knee surgery for middle-aged and older patients with degenerative meniscal tears with or without concomitant radiographic knee osteoarthritis (OA). We investigated the prevalence of early or more established knee OA and patients’ characteristics in a cohort of patients undergoing arthroscopic surgery for a meniscal tear.

Patients and methods — 641 patients assigned for arthroscopy on suspicion of meniscus tear were consecutively recruited from February 2013 through January 2015. Of these, 620 patients (mean age 49 (18–77) years, 57% men) with full datasets available were included in the present study. Prior to surgery, patients completed questionnaires regarding onset of symptoms, duration of symptoms, and mechanical symptoms along with the knee injury and osteoarthritis outcome score (KOOS). At arthroscopy, the operating surgeon recorded information about meniscal pathology and cartilage damage. Early or more established knee OA was defined as the combination of self-reported frequent knee pain, cartilage damage, and the presence of degenerative meniscal tissue.

Results — 43% of patients (269 of 620) had early or more established knee OA. Of these, a large proportion had severe cartilage lesions with almost half having a severe cartilage lesion in at least 1 knee compartment.

Interpretation — Based on a definition including frequent knee pain, cartilage damage, and degenerative meniscal tissue, early or more established knee OA was present in 43% of patients undergoing knee arthroscopy for meniscal tear.     

Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis

OBJECTIVE: To evaluate the effect of calcitonin (CT) on the histology and biochemistry of articular cartilage from unstable operated and nonoperated knee in a canine model of experimental osteoarthritis (OA). METHODS: Eighteen dogs underwent anterior cruciate ligament transection (ACLT) of the right knee and were randomly distributed into three groups of six dogs each. From day-1 after surgery until sacrifice 84 days post-ACLT, each dog received a daily nasal spray that delivered the placebo, 100 units of CT or 400 units of CT. Histologic lesions were scored. Hyaluronan (HA) and antigenic keratan sulfate (AgKS) were quantified by enzyme-linked immunosorbent assays (ELISAs), whereas aggrecan molecules extracted under nondissociative conditions were characterized by velocity gradient centrifugation. RESULTS: All canine cruciate-deficient knees developed OA. At a daily dose of 400 units, CT had no effect on the size of osteophytes but significantly reduced the severity of cartilage histologic lesions in unstable knees. CT also enhanced the HA content as well as the size distribution and relative abundance of fast-sedimenting aggrecan aggregates in cartilage from both operated and nonoperated knees. On the other hand, in the CT-treated group, the cartilage content of AgKS increased in operated joints, but not in nonoperated joints. CONCLUSIONS: Because CT delivered as a nasal spray markedly reduced the severity of most OA changes, both at the histological and biochemical level, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury, and as well as for dogs who spontaneously rupture their ACL.     

Femoral lengthening might impair physical function and lead to structural changes in adjacent joints: 10 patients with 27 to 34 years’ follow-up

Background and purpose — Literature describing long-term functional outcome and osteoarthritis (OA) in adjacent joints after femoral lengthening is rare. We evaluated physical function and the presence of radiographic OA in adjacent joints in 10 patients ≥ 27 years after femoral lengthening.Patients and methods — We conducted a cross-sectional study of 10 patients treated by unilateral femoral lengthening. Follow-up was between 27 and 34 years. Physical function was evaluated by the 30-second sit-to-stand (30sSTS) and a stair test and was compared with reference values. 4 single-legged hop tests were used to assess difference in physical function between the lengthened and contralateral limb. Radiographic OA was evaluated by joint space width (JSW) and Kellgren and Lawrence (KL) classification.Results — The patients scored worse compared with reference values on the 30sSTS and stair test, and worse on the lengthened limb on the single- and triple-hop test. Radiographic OA was found in the hip or knee in the lengthened limb in 3 of 10 patients based on JSW and 4 of 10 based on KL. No radiographic OA was found in unlengthened limbs.Interpretation — Our results showed impaired physical function both in general and of the lengthened limb. Additionally, we found a possible association between femoral lengthening and radiographic OA in adjacent joints in the long term. However, the sample size of the current study is small.

Limb lengthening by the callotasis technique is a well-established method for treatment of leg length discrepancy (LLD). However, literature describing the long-term functional outcome and eventual late side effects such as osteoarthritis (OA) in adjacent joints is rare. Previous studies have investigated whether femoral lengthening impacts muscle strength in the lengthened limb, but results are inconsistent (Bhave et al. 2017, Krieg et al. 2018). Concerns have been raised regarding whether limb lengthening might lead to OA in adjacent joints (Herring 2008, Sneppen et al. 2014). However, to our knowledge there is only 1 published article describing articular damage after femoral lengthening by the callotasis technique. In this animal study, Stanitski (1994) found cartilage injury in the knees of all included canines after completing 30% distraction of initial femoral length. Even though this animal research showed knee OA after limb lengthening this is yet to be studied in humans. We evaluated physical function and the presence of radiographic signs of OA in the adjacent hip and knee joints ≥ 27 years after unilateral femoral lengthening by the callotasis technique. We hypothesized that femoral lengthening was associated with reduced physical function and OA in adjacent joints.     

Can meniscus refixation prevent early development of arthrosis in the knee joint? Long-term results

This retrospective study presents the long-term results after meniscal repair with emphasis on early-development of osteoarthritis in the knee. From 1984 to 1996 meniscal repair using the inside-out technique was performed on 54 patients. 25 patients had an isolated tear of the meniscus and 29 additionally a tear of the anterior cruciate ligament (ACL, combined injury). 18 patients of those with a combined injury showed a stable knee during clinical follow-up. A separate evaluation of this group was carried out. The mean follow-up was 6.4 years. 22 patients were examined over a period of 2-5 years (mean 3.5) after surgery, 32 patients after 5 years (mean 8.9). The clinical evaluation was carried out using IKDC, Tegner activity scale, Lysholm, and Tapper and Hoover-Score as well as the Fairbank radiographic evaluation. According to the Fairbank's evaluation the results show that up to 5 years after meniscal repair only minimal radiographic changes were detectable. In only 21% of patients with an isolated meniscal lesion and in 13% of those with a stable knee after a combined injury beginning of osteorathritic changes were noted more than 5 years postoperatively. Early osteoarthritic changes were present within 5 years after surgery in non-stable knees (untreated rupture, suturing). Patients with meniscal repair mostly regain their original Tegner activity level and good to very good results in the clinical scores. However, the results clearly indicate that the success of meniscal repair depends on the stability of the knee. Thus, meniscal repair in stable knees is recommended to prevent early development of osteoarthritis.     

Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study

Traumatic knee injuries often result in damage to articular cartilage and other joint structures. Such trauma is a strong risk factor for the future development and progression of osteoarthritis (OA). The molecular mechanisms and signaling pathways modulating response to knee joint trauma remain unclear. Moreover, investigations of biomarkers influencing responses have been targeted rather than broad, unbiased discovery studies. Herein, we characterize the complete complement of extracellular RNA (exRNA) in the synovial fluid of 14 subjects following knee injury. Fluid was collected during surgery from the injured knees, and from the contralateral knee in a subset, undergoing surgical repair of the ACL and/or meniscal repair/debridement. Arthroscopic grading of chondral damage in four knee compartments was performed using the Outerbridge classification. exRNA was extracted and subjected to massively parallel total RNA sequencing. Differential abundance of RNA was calculated between the subject cohorts of injured and non‐injured knee, average Outerbridge score ≥0.5 and less, and chronic and acute injury duration defined as ≤4 months till surgery or longer. Overall, expression of several thousand genes was identified in the synovial fluid. Furthermore, differential expression analysis suggests a role of exRNA fragments of matrix metalloproteinases and skeletal muscle fiber genes in the response to traumatic injury. Together, these data suggest that high‐throughput approaches can indicate exRNA molecular signatures following knee trauma. Future studies are required to more fully characterize the biological roles of these exRNA and the cadence of their respective release that may lead to translational treatment options for post‐traumatic OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1659–1665, 2018.

     

The Nonoperative Treatment of Acute, Isolated (Partial or Complete) Posterior Cruciate Ligament-Deficient Knees: An Intermediate-term Follow-up Study

Fifty-seven consecutive patients (58 knees) with an acute, isolated, posterior cruciate ligament (PCL) injury were treated nonoperatively. Clinical, radiographic, and functional assessment was performed at a mean follow-up of 6.9 years (range 2 to 19.3 years) after the initial diagnosis. At the time of initial documentation of the injury, the posterior drawer test was grade A in 17 knees and grade B in 41 knees. The mean preinjury Tegner activity level was 7 (range 4 to 10). At latest follow-up, 38 knees had no pain, 14 had mild pain, and 6 had moderate pain on exertion. Fifty-four knees had no swelling, 3 had mild, intermittent swelling, and 1 had a moderate swelling on exertion. The posterior drawer test was grade A in 14 knees and grade B in 44 knees. The mean Lysholm-II knee score was 85.2 points (range 51 to 100 points) and the mean Tegner activity level was 6.6 (range 3 to 10). Based on Lysholm-II knee scoring system, the results were excellent in 23 knees (40%), good in 30 knees (52%), fair in 2 knees (3%), and poor in 3 knees (5%). No statistically significant correlation (p = 0.097) was seen between the grade of PCL laxity and Lysholm-II knee score. Plain radiographs showed mild (grade I) medial compartment osteoarthritis (OA) in 7 knees, and moderate (grade II) medial compartment OA in 3 knees. Mild patellofemoral OA was seen in 4 knees. We believe that most patients with acute, isolated PCL injuries do well with nonoperative treatment at a mean follow-up of 6.9 years. The level of evidence for this retrospective cohort study is level III.     

Effects of articular cartilage and meniscus injuries at the time of surgery on osteoarthritic changes after anterior cruciate ligament reconstruction in patients under 40?years old

Introduction  The development of osteoarthritis (OA) after anterior cruciate ligament (ACL) reconstruction is an unsolved problem. Articular cartilage and meniscus injuries are particularly important factors that contribute to OA progression. Aim  The purpose of this study was to investigate how articular cartilage and meniscus injuries at the time of surgery affected the development of OA under limited conditions retrospectively. Exclusion criteria of this study were (1) age 40 years or over, (2) previous surgery, (3) another combined knee ligament injury, and (4) unstable reconstructed knees. Material  This study included 49 knees in 46 patients (average 26 years; range, 13–39 years) who had undergone isolated ACL reconstruction. Mean follow-up period was 3.9 years (range, 2–8 years). We classified patients into two groups, cartilage-damaged and non-damaged. Patients were also classified into two groups on the basis of treatment for meniscus: meniscectomy group and meniscus intact group. OA changes were investigated using weigh-bearing anteroposterior radiographs taken before surgery and at evaluation. OA changes were evaluated in terms of joint space narrowing, atrophy, sclerosis, cysts, spurs, flattening of the femoral condyle, concavity of the tibial condyle, and sharpening of the eminence. Each parameter was scored, and the total number of points was recorded as the OA score. Results  Differences between the preoperative OA score and that at evaluation were defined as the increase of the OA score. OA progressed in 28 knees (57%). OA score was higher at evaluation than before surgery (P < 0.001). In the cartilage-damaged group, the Lysholm score at evaluation was lower (P < 0.05) and the increase in the OA score was higher than in the non-damaged group (P < 0.05). The increase in the OA score was higher in the meniscectomy group (P < 0.05). Conclusion  We concluded that patients with cartilage damage and who had undergone meniscectomy show more progression of OA. These patients require long-term follow-up. Level of evidence  Level 4, case series, therapeutic studies, investigating the results of treatment. Presented at 6th Biennial Congress of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine.     

Relationship between synovial fluid biomarkers of articular cartilage metabolism and the patient's perspective of outcome depends on the severity of articular cartilage damage following ACL trauma

Anterior cruciate ligament (ACL) trauma often occurs in combination with injury to the articular cartilage of the knee, this can result in earlier radiographic evidence of post traumatic osteoarthritis (OA) of the knee compared to the contralateral, ACL intact knee; however, the biomechanical and biological mechanisms associated with the onset and progression of this disease are not understood. We sought to gain insight into the mechanisms by determining the relationship between articular cartilage injury associated with ACL trauma and the expression of synovial fluid biomarkers of articular cartilage metabolism, and to evaluate the relationship between these biomarkers and the patient's perspective of the outcomes. Synovial fluid samples were acquired from 39 ACL injured subjects at an average of 10 weeks after injury, and 32 control subjects with normal knees (documented with clinical exam and MRI assessment). Subjects in the ACL‐injured group were classified as low‐risk for future OA if they displayed an International Cartilage Repair Society (ICRS) Grade 2 articular cartilage lesion or less and high‐risk for future OA if they had an ICRS Grade 3A articular cartilage lesion. The patient's perspective of the injury was evaluated with the Knee Injury and Osteoarthritis Outcomes Score (KOOS). There were no significant differences in mean concentrations of the markers of type II collagen metabolism (CPII, C2C, and C1,2C) or the aggrecan breakdown Alanine–Arginine–Glycine–Serine (ARGS) ‐fragment between control subjects and the subjects in the low‐ and high‐risk groups (p‐value range: 0.80–0.43). Associations between ARGS‐aggrecan concentration and KOOS subscales of symptoms and pain were significantly different between the low‐ and high‐risk groups (p = 0.03 and p = 0.01, respectively). Likewise, there was strong evidence in support of an association between the markers of type II collagen metabolism (C1,2C and CPII concentrations) and the KOOS subscale of pain between the low‐ and high‐risk groups (p = 0.051 and 0.077, correspondingly). In ACL injured subjects with concomitant Grade 3A articular cartilage injuries, concentrations of synovial fluid ARGS‐aggrecan were directly associated with improvements in KOOS symptoms and pain. These findings suggest the possible involvement of ARGS‐aggrecan in a localized tissue repair response involving an increase in aggrecan turnover following severe knee trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:820–827, 2016.