Ryuichiro Akagi

Hidden osteophyte formation on plain X-ray is the predictive factor for development of knee osteoarthritis after 48 months – data from the Osteoarthritis Initiative

OBJECTIVE To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.

Effective knock down of matrix metalloproteinase-13 by an intra-articular injection of small interfering RNA (siRNA) in a murine surgically-induced osteoarthritis model

This study investigated the effect of MMP‐13 gene knock down on cartilage degradation by injecting small interfering RNA (siRNA) into knee joints in a mouse model of osteoarthritis (OA). OA was induced in male C57BL/6 mice by destabilization of medial meniscus (DMM) surgery. Change of Mmp13 expression over time was determined by qPCR analysis from 3 days to 6 weeks after surgery. Mmp13 and control chemically modified siRNA were injected into the knee joint 1 week after surgery and expression levels were assessed in synovium by qPCR 48 h later. Cartilage degradation was histologically assessed 8 weeks after DMM surgery according to OARSI recommendations. Mmp13 expression levels were elevated 1 week after surgery and peaked at 77 fold at 2 weeks compared to expression at 3 days. A 55% decrease of Mmp13 levels in cartilage was observed 48 h after injection of Mmp13 siRNA (p = 0.05). Significant reduction in the histological score at 8 weeks after surgery was observed in the Mmp13 siRNA‐treated group compared to the control siRNA group (p < 0.001). Intra‐articular injection of Mmp13 siRNA at the early phase of OA development resulted in effective knock down of Mmp13 expression and delay in cartilage degradation in vivo.

Two cases of synovial haemangioma of the knee joint: Gd-enhanced image features on MRI and arthroscopic excision

Synovial haemangioma of the knee joint is a relatively rare benign condition with around 200 reported cases. We have recently encountered two cases of synovial haemangioma of the knee joint which preoperative MRI had assessed as highly suspect and which arthroscopic resection and subsequent histological examinations confirmed as synovial hemangiomas. Published studies have identified the following as characteristic MRI features of synovial haemangioma: homogenous low intensity to iso-intensity on T1 sequence; and heterogeneous high intensity with low-intensity septa or spots within the lesion on T2 sequence. However, several other intra-knee disorders mimic these characteristics. In our two cases, we found that gadolinium (Gd)-enhanced images, which have been relatively rarely discussed in the literature, were useful for making the diagnosis and for determining the extent of this condition. These images also were very helpful during arthroscopic excision of the lesion. Nonetheless, even after Gd enhancement, differentiating between malignant conditions such as synovial sarcoma and haemangioma solely from MRI findings is still difficult.

Comparison of early and late surgical intervention for lumbar disc herniation: is earlier better?

BackgroundThe optimal timing for surgical intervention in cases of lumbar disc herniation is debatable. This retrospective study sought to determine whether early surgical intervention resulted in greater improvement in clinical outcomes.MethodsA total of 46 patients with lumbar disc herniation treated by microendoscopic discectomy were reviewed. Surgery was performed when leg pain persisted despite adequate conservative treatment. The patients were divided into two groups according to the duration of symptoms before surgery, the early group being symptomatic for ≤3 months and the late group for >3 months. Surgical time, blood loss, severity of back pain, leg pain and numbness (visual analogue scale, or VAS), and a patient-oriented evaluation score (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, or JOABPEQ) before and after surgery were compared. The JOABPEQ is a new evaluation method for lumbar spinal disorders based on Roland-Morris disability questionnaires and Short Form 36.ResultsThere were 23 patients in each group. No significant differences were found between the groups in patients’ demographics (age, sex, type of herniation), surgical time, blood loss, or pre- and postoperative VAS (lower-back pain, leg pain, numbness). There were no significant differences between the groups in the scores for the five subscales — pain-related disorders, gait disturbance, lumbar spine dysfunction, social life disturbance, psychological disorders — of the preoperative JOABPEQ. Postoperative scores for psychological disorders improved significantly (P < 0.05) in the late group (mean score 39.9) compared to the early group (mean score 22.1). Interestingly, no significant difference of improvement in the scores other than psychological disorder was found between the two groups.ConclusionsEarly surgical intervention did not result in greater improvement of clinical outcomes for patients with lumbar disc herniation. Later surgical intervention resulted in significant improvement of psychological disorders.

Quantitative Assessment of Tendon Healing by Using MR T2 Mapping in a Rabbit Achilles Tendon Transection Model Treated with Platelet-rich Plasma.

PURPOSE To determine if magnetic resonance (MR) imaging T2 mapping can be used to quantify histologic tendon healing by using a rabbit Achilles tendon transection model treated with platelet-rich plasma (PRP). MATERIALS AND METHODS Experiments were approved by the Institutional Animal Care and Use Committee. The Achilles tendons of 24 New Zealand white rabbits (48 limbs) were surgically transected, and PRP (in the test group) or saline (in the control group) was injected into the transection site. The rabbits were sacrificed 2, 4, 8, and 12 weeks after surgery. Thereafter, T2 mapping and histologic evaluations were performed by using the Bonar scale. A mixed-model multivariate analysis of variance was used to test the effects of time and PRP treatment on the T2 value and Bonar grade, respectively. The correlation between the T2 value and Bonar grade was also assessed by using the Spearman correlation coefficient. RESULTS The Bonar scale values decreased in both groups during tendon healing. The T2 value also shortened over time (P < .001 for both groups). The T2 values were positively correlated with the Bonar grade (ρ = 0.78, P < .001). Both the T2 value and Bonar scale value were lower in the PRP group than in the control group at 4, 8, and 12 weeks; however, there was no significant effect of PRP treatment on the T2 value or Bonar grade. CONCLUSION The T2 value changes reflected histologic tendon healing. While T2 and Bonar grade were lower at all time points in tendons treated with PRP, there was no significant difference between the treatment and control tendons.

Accuracy of high-resolution ultrasound in the detection of meniscal tears and determination of the visible area of menisci.

BACKGROUND Imaging is of great importance in diagnosing meniscal tears. The aim of this study was to assess the accuracy of high-resolution ultrasound in the diagnosis of meniscal tears, with arthroscopic examination as the standard reference, after resolution was confirmed with a target-mounted reference phantom. An additional goal was to elucidate the area of the meniscus that could be visualized with the same ultrasound machine after placement of markers into the menisci of cadaveric knees. METHODS Seventy patients were included for the assessment of the accuracy of a high-resolution ultrasound machine with a 14.0 to 6.0-MHz linear transducer. The preoperative ultrasound diagnosis, in terms of the presence and type of tear, was compared with that in the surgical reports. In the cadaveric studies, nine needles were placed in the peripheral zone of the menisci at regular intervals and the number of needles that could be observed with the system was recorded. RESULTS The overall sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound examination for meniscal tears were 88%, 85%, 85%, and 88%, respectively. These statistical parameters did not differ significantly between the medial and lateral menisci. The sensitivity for diagnosing horizontal, vertical, radial, flap, bucket-handle, and complex tears and for detecting discoid lateral menisci was 83%, 64%, 0%, 64%, 54%, 90%, and 80%, respectively. Ten percent of the lateral menisci could not be evaluated because of poor images. The cadaveric studies revealed that the ultrasound visualized the entire meniscus except for the anterior horn. CONCLUSIONS The findings of this study suggest that ultrasound examination may be suitable for screening for meniscal tears. The fact that almost 10% of the lateral menisci could not be evaluated because of poor images appears to be a weakness of ultrasound.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model

OBJECTIVE Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. DESIGN OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. RESULTS Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. CONCLUSION IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

OBJECTIVE To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. DESIGN Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. RESULTS Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). CONCLUSION T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.

Distribution of hip pain in patients with idiopathic osteonecrosis of the femoral head

Abstract Objective: To determine the distribution of referred hip pain in patients with idiopathic osteonecrosis of the femoral head (ION). Methods: We prospectively documented 119 hips in 90 patients with ION (mean age 51 years). Patients identified the location of pain originating in their hip on a drawing of the body. Osteoarthritis of the hip (OA) was used as a historical cohort. Results: Referral of pain originating from the hip in patients with ION was 93% (111 hips) to the groin, 68% (81 hips) to the knee, 36% (43 hips) to the anterior thigh, 34% (40 hips) to the buttock, 18% (22 hips) to the lower leg, 9% (11 hips) to the greater trochanter, and 8% (9 hips) to the low back. About 97% (115 hips) of pain was located in the hip region (groin, buttock, and greater trochanter) and 77% (92 hips) showed referred pain (anterior thigh, knee, lower leg, and low back). Pain from ION was significantly more frequent in the knee and lower leg, but significantly less frequent in the lower back than pain from OA. Conclusion: We should be aware of ION masquerading as pain in the knee or anterior thigh.

Natural history of popliteal cysts in the pediatric population.

Background: Cystic mass lesions in the popliteal area, called popliteal cysts or Baker’s cysts, are usually minimally symptomatic and not related to intra-articular morbidity in the pediatric population. Although multiple studies have described cases of spontaneous resolution over a period of several months to a few years, others still consider surgical treatment necessary. Furthermore, no previous studies have used magnetic resonance imaging (MRI) to confirm the disappearance of popliteal cysts. In this retrospective study, we reviewed records of patients with popliteal cysts to investigate the natural history of this disease. Methods: The medical records of patients with popliteal cysts followed for at least 12 months were retrospectively reviewed. The patient set comprised of 17 knees in 15 males and 3 knees in 2 females. Mean age was 5.6±2.0 years (range, 1.8 to 11.4 y) at their initial visit to the clinic, and mean follow-up period was 53.1±31.6 months (range, 12.6 to 147.8 mo). MRI findings were reviewed for the 16 knees in 13 patients who had undergone MRI. Symptoms and clinical course were extracted from the medical records of all the study subjects and analyzed. Results: Although 6 knees (30%) had histories of pain in the popliteal area, no patient complained of pain at their initial visit. Seventeen cysts (85%) naturally decreased in size or disappeared on clinical examination and/or ultrasound. Cysts confined to either the gastrocnemio-semimembranosus bursa or the subgastrocnemius bursa according to the MRI findings were classified as type I, and cysts which occupied both bursae were classified as type II. Eight knees received MRI examination more than once, and complete disappearance was confirmed in 5 of these knees. All type II cysts converted to type I, and all cysts which completely disappeared were type I before disappearance. Conclusions: The MRI findings in our study population confirmed that popliteal cysts in pediatric populations can be expected to completely resolve in due course without treatment. Level of Evidence: Therapeutic study Level IV (Case series).