Summary

This study shows a significant reduction in knee adduction moment in patients with medial compartment osteoarthritis, in both the symptomatic and asymptomatic knees. Long-term follow-up studies are required to confirm the effect of treating the asymptomatic side on disease progression.

Introduction

Greater trochanteric pain syndrome (GTPS) is a common and disabling condition characterised by pain and tenderness at or around the trochanteric area. Extracorporeal shockwave therapy (ESWT) has been described as a method of treatment. The National Institute for Clinical Excellence (NICE, UK) guidance suggests a possible benefit but with limited evidence.

Background

The knee is the commonest joint to be affected by osteoarthritis, with the medial compartment commonly affected. Knee osteoarthritis is commonly bilateral, yet symptoms may initially present unilaterally. Higher knee adduction moment has been associated with the development and progression of medial compartment knee osteoarthritis.

BACKGROUND

High tibial Osteotomy (HTO) realigns the forces in the knee to slow the progression of osteoarthritis. This study relates the changes in knee joint biomechanics during level gait to glutamate signalling in the subchondral bone of patients pre and post HTO. Glutamate transmits mechanical signals in bone and activates glutamate receptors to influence inflammation, degeneration and nociception in arthritic joints. Thus glutamate signalling is a mechanism whereby mechanical load can directly modulate joint pathology and pain.

Glutamate is a neurotransmitter that transmits mechanical signals in bone (1) and activates glutamate receptors and transporters, in bone, cartilage, meniscus and synovium (2). Glutamate receptor activation influences inflammatory, degenerative and nociceptive pathways in arthritic joints (2). Thus glutamate signalling is a mechanism whereby mechanical load can directly influence joint pathology and pain. We have investigated components of glutamate signalling in the subchondral bone of patients with osteoarthritis to determine which are expressed and whether this varies in anatomical regions subject to different loads. Subchondral bone was sampled from tibial cuts derived from total knee arthroplasty (n=2, TKR, Kellgren Lawrence grade 3) and from tibial drill hole sites from high tibial osteotomy (n=5, HTO, KL grades 2 and 3) for osteoarthritis. RNA was extracted, reverse transcribed and RT-PCR performed for a housekeeping gene GAPDH, a glutamate transporters (EAAT-1, EAAT1ex9skip), glutamate receptors (NR2A and KA1), a bone matrix protein, osteocalcin, and signaling molecules (osteoprotegerin [OPG], RANKL). We found differential mRNA expression in different regions of subchondral bone. In one TKR patient, EAAT-1 expression was significantly reduced in the anterior zone versus the middle or posterior zones of the tibial plateau (ANOVA, p<0.001). HTO bone cores were subdivided medial/lateral and anterior/posterior. Good quality RNA was obtained from bone cores removed from drill holes during HTO surgery, with GAPDH, osteocalcin, EAAT-1, EAAT1ex9skip, NR2A, KA1, OPG and RANKL mRNA expression detected. In one patient, comparison of gene expression in bone cores obtained pre and post HTO revealed that EAAT1ex9skip was rarely detected in post-op bone whereas KA1 was rare in pre-op bone. This differential mRNA expression may be due to the altered loading through the joint caused by the osteotomy, although these on/off differences need to be quantified to confirm this.

We have shown that glutamate transporters and receptors are expressed in human subchondral bone. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate released in arthritis will influence pathological changes and nociception. In some patients, glutamate transporter mRNA expression appears to vary with anatomical location in bone, or after HTO surgery, consistent with our original discovery of this transporter as mechanically-regulated in bone (1). If glutamatergic signaling is mechanically regulated in the human knee, this will vary during arthritic disease progression and after joint realignment, providing a direct mechanism linking mechanical loading through the joint to pathology and pain in arthritis.

Background: Distinguishing septic arthritis from transient synovitis of the hip in children can be both crucial and challenging. In 1999, Kocher et al suggested four clinical predictors, fever > 38.5°C, inability to weight bear, WBC count > 12.0x109/L, and ESR> 40mm/hr; that, when combined were highly predictive of septic arthritis in children (99.6%). This figure was challenged by Luhmann et al, stating that the clinical prediction did not exceed 59%. In 2006, Caird et al recommended adding CRP of > 20mg/L as a fifth predictor.

Aims: To assess the value and accuracy of clinical prediction algorithms in distinguishing septic arthritis from transient synovitis of the hip in children in our hospital.

Methods: A retrospective review of all children admitted to our institution with painful hips was carried out over a period of four years (Feb 2003 to Mar 2007). One-hundred and twenty-two admissions (115 patients, 7 re-admissions) were reviewed.

Results: 79 patients (64.8%) were males. The mean age was 6 years (9 months to 15 years).

86 patients (70.5%) were diagnosed with transient synovitis. All the 7 re-admissions were from this group. Only one of the re-admissions was diagnosed with confirmed septic arthritis.

4 patients (3.3%) were diagnosed with definite septic arthritis with positive cultures from the hip, and 1 (0.8%) with probable septic arthritis (negative culture).

The presence of the clinical predictors was compared between the transient synovitis and septic arthritis groups, using Fisher’s exact test. Only the raised temperature and CRP were found to be significantly different (p< 0.05).

Only two children (40%) with confirmed septic arthritis had four or more predictors (one had all five, and the other was able to partially weight bear). The third child had a raised temperature and CRP, and the fourth had a raised temperature only. The fifth patient (20%) was diagnosed with probable septic arthritis. His cultures were negative, but he was already on intravenous antibiotics. This patient did not have any of the predictors on admission (temperature was 38.3°C, CRP 10.7). However, he spiked a temperature of 40°C 24 hours post admission despite being on antibiotics, and his CRP increased to 34.5mg/L.

In the transient synovitis group, two patients (2.2%) had positive five predictors, but were proven to have transient synovitis secondary to a urinary tract infection and gastroenteritis. 47 patients (51.6%) did not have any of the predictors, and 6 patients (6.6%) had three or more positive predictors.

Conclusion: Although clinical predictors are helpful in distinguishing septic arthritis from transient synovitis, there were false negative and false positive findings in the study. The predictors cannot be considered alone, and ultimately clinical judgement must be exercised to ensure that cases of septic arthritis are not missed.

The crucial differentiation between septic arthritis and transient synovitis of the hip in children can be difficult. In 1999, Kocher et al introduced four clinical predictors which were highly predictive (99.6%) of septic arthritis. These included fever (temperature ≥ 38.5°C), inability to bear weight, white blood-cell count > 12.0 × 10⁹ cells/L and ESR ≥ 40 mm/hr; CRP ≥ 20 mg/L was later added as a fifth predictor. We retrospectively evaluated these predictors to differentiate septic arthritis from transient synovitis of the hip in children over a four-year period in a primary referral general hospital. When all five were positive, the predicted probability of septic arthritis in this study was only 59.9%, with fever being the best predictor. When applied to low-prevalence diseases, even highly specific tests yield a high number of false positives and the predictive value is thereby diminished.

Clinical predictors should be applied with caution when assessing a child with an irritable hip, and a high index of suspicion, and close observation of patients at risk should be maintained.