Camptodactyly-arthropathy-coxa vara-pericarditis syndrome and an unusual association with mitral stenosis.

BACKGROUND: Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the fifth finger (camptodactyly); noninflammatory arthropathy; decreased angle between the shaft and the head of the femur (coxa vara) and pericarditis. Its association with mitral stenosis has not yet been reported. Hereby we report this unique association with CACP syndrome. CASE: An eleven-year-old girl presented with non-productive cough, dyspnea, and orthopnea. She was diagnosed CACP syndrome at the age of seven and a biallelic frameshift mutation in the PRG4 gene was determined. The physical examination revealed pectus excavatum, camptodactyly, genu valgum, tachypnea and orthopnea. The functional capacity was NYHA III-IV. She had 2/6 soft pansystolic murmur at 4th left intercostal space and a rumbling diastolic murmur at apex. Echocardiography revealed an enlarged left atrium, severe stenotic mitral valve with a mean diastolic transmitral gradient of 22.5 mmHg, mild mitral regurgitation and mild apical pericardial effusion. The patient had mitral comissurotomy and partial pericardiectomy operation. Her post-operative transmitral gradient decreased to 6.9 mmHg and the pulmonary pressure was 30 mmHg. Her functional capacity increased to NYHA I-II. CONCLUSIONS: The main defect is the proteoglycan 4 protein which acts like a lubricant in articular and visceral surfaces. Therefore, the leading clinical feature is arthropathy. Cardiac involvement other than clinically mild pericarditis is not usually expected. Three types of proteoglycans (decorin, biglycan, and versican) are present in the mitral valve. This could be the reason of mitral valve involvement in rare cases as like ours. It is important that these patients undergo echocardiographic examination regularly.

Open reduction versus closed reduction in internal fixation of displaced femoral neck fracture in children: a systematic review and meta-analysis.

BACKGROUND: The quality of reduction is an important factor affecting clinical outcomes for displaced femoral neck fractures (FNFs). However, concerns remain about the invasiveness of open reduction and internal fixation (ORIF) as compared to that of closed reduction and internal fixation (CRIF), and the choice between ORIF and CRIF as an optimal treatment strategy for displaced pediatric FNF remains controversial. MATERIALS AND METHODS: MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published up to December 22, 2022, that compared ORIF and CRIF techniques for treating FNF in children. Pooled analysis identified differences in surgical outcomes between ORIF and CRIF, especially regarding postoperative complications, such as osteonecrosis of the femoral head (ONFH), nonunion, coxa vara deformity, leg-length discrepancy LLD, and premature physeal closure (PPC). RESULTS: We included 15 studies with 635 pediatric FNF cases in our review. Of these, 324 and 311 were treated with ORIF and CRIF, respectively. The pooled analysis revealed that no significant differences existed between each reduction technique for ONFH (odds ratio [OR] = 0.89; 95% confidence interval [CI] 0.51-1.56; P = 0.69), nonunion (OR = 0.51; 95% CI 0.18-1.47; P = 0.21), coxa vara deformity (OR = 0.58; 95% CI 0.20-1.72; P = 0.33), LLD (OR = 0.57; 95% CI 0.18-1.82; P = 0.35), and PPC (OR = 0.72; 95% CI 0.11-4.92; P = 0.74). CONCLUSIONS: Despite concerns about the invasiveness of ORIF, no differences in complications exist between ORIF and CRIF after FNF in children. Therefore, we believe that ORIF should be performed in FNF when the fracture is irreducible by closed manner.

Adult Idiopathic Bilateral Coxa Vara with Hip Osteoarthritis Treated with Bilateral Proximal Femur Osteotomy: A Case Report.

CASE: We reported a case of a 25-year-old woman with idiopathic bilateral coxa vara who had initial presentation of hip osteoarthritis. She was later treated with bilateral subtrochanteric valgus osteotomy. A good functional outcome was recorded without nonunion or deformity recurrence. The arthritis of the hips also decelerated. CONCLUSIONS: Coxa vara first diagnosed in adulthood was relatively uncommon, and the cause in this present case was uncertain. Subtrochanteric valgus osteotomy seemed to be a suitable treatment for this case.

Acute and mid-term (six-week) effects of an ankle-foot-orthosis on biomechanical parameters, clinical outcomes and physical activity in knee osteoarthritis patients with varus malalignment.

BACKGROUND: Knee osteoarthritis (KOA) is a painful disease commonly caused by high loads on the articular cartilage. Orthotic interventions aim to reduce mechanical loading, thereby alleviating pain. Traditional orthotics appear effective, but high drop-out rates have been reported over prolonged periods. RESEARCH QUESTION: The aim of this study was to examine the effect of a novel ankle-foot orthosis (AFO) on gait parameters, physical function and activity of KOA patients. METHODS: 29 clinically diagnosed KOA patients with varus malalignment wore an AFO for 6 weeks. Prior to and after the intervention period, 3D gait analysis, physical function tests and the KOOS questionnaire were administered. Physical activity was objectively assessed with accelerometers. RESULTS: The AFO immediately reduced the first peak of the knee adduction moment (KAM) and the KAM impulse by 41% and 19%. The knee flexion moment (KFM) was increased by 48%. After six weeks, the first KAM peak and KAM impulse were decreased by 27% and 19% while using the AFO. The KFM was increased by 71%. Furthermore, patients completed the functional tests faster (1.4-2.6%). The KOOS scores decreased significantly. No significant differences were found in physical activity parameters. SIGNIFICANCE: The six-week AFO application significantly reduced the KAM. The patients' physical function appeared improved; yet these improvements were only minor and therefore arguably clinically irrelevant. The KFM appeared to be negatively affected after six weeks, as were the scores on the KOOS subscales. In summary, even though the AFO reduced the KAM and improved physical function, the clinical benefit for KOA patients with varus malalignment after the 6-week AFO application is debatable.

Using a Tibial Short Extension Stem Reduces Tibial Component Loosening After Primary Total Knee Arthroplasty in Severely Varus Knees: Long-term Survival Analysis With Propensity Score Matching.

BACKGROUND: Patients with severe preoperative varus deformity have been reported to have high rates of loosening after total knee arthroplasty (TKA), primarily on the tibial side. This study investigated whether a short extension stem for the tibial component in severely varus knees would reduce the failure rate due to loosening on the tibial side. METHODS: Patients who underwent TKA, performed by a single surgeon using a single implant between November 1998 and January 2009, were retrospectively evaluated. Patients diagnosed with primary osteoarthritis, having a hip-knee-ankle axis greater than varus 8° on preoperative long-film radiographs, and postoperatively followed up for more than 2 years were included. Patients were divided into "stem" and "nonstem" groups, followed by 1:1 propensity score matching according to age, gender, body mass index, preoperative mechanical axis, and postoperative alignment. Tibial loosening rates in the 2 groups were compared. RESULTS: The study cohort included 602 patients, divided into "stem" and "nonstem" groups. Propensity score matching yielded 88 pairs of patients. Mean follow-up duration was similar in the stem and nonstem groups (109.22 vs 103.81 months, P = .451). None of the patients in the stem group, compared with 5 in the nonstem group, experienced aseptic loosening. The overall implant survival rate was significantly higher in the stem group than in the nonstem group (P = .0201). CONCLUSION: Using a short extension stem for the tibial component in primary TKA in patients with severe varus deformity greater than 8° may reduce the rate of loosening of the tibial side and increase the longevity of the implant. LEVEL OF EVIDENCE: Level III.

Protein-losing enteropathy in camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.

BACKGROUND: Camptodactyly-arthropathy-coxa vara-pericarditis (CACP, OMIM: #208250) syndrome is a rare autosomal recessive disease that can be difficult to recognise not only because of its wide clinical variability but also because of its clinical resemblance to juvenile idiopathic arthritis (JIA). PRG4 is the only gene so far known to be associated with CACP syndrome. Children with CACP syndrome lack the glycoprotein lubricin due to recessive mutations in PRG4. Lubricin serves as a lubricant in joints, tendons and visceral cavities (pleural cavity, pericardium) and inhibits synovial proliferation. Children with CACP syndrome suffer from congenital camptodactyly, arthropathy, coxa vara and sometimes pericarditis. This report concerns a child with CACP syndrome complicated by protein-losing enteropathy (PLE), caused by constrictive pericarditis and so contributes to knowledge of the presentation of CACP syndrome. CASE PRESENTATION: A 10- year-old girl with consanguineous parents suffered from congenital camptodactyly and progressive swollen and painful joints. Her father and his sister had similar childhood-onset joint complaints. Laboratory tests showed no signs of inflammation but showed persistent low protein- and IgG- levels, indicating a secondary immunodeficiency. Increased alpha antitrypsin clearance confirmed PLE. Abdominal ultrasound with Doppler showed hepatomegaly and portal hypertension. Echocardiography suggested constrictive pericarditis. However, heart catheterization could not confirm this. Ultrasound and X-ray examination of the joints combined with a puncture of the synovial fluid were performed. These results, combined with the clinical presentation and the consanguinity, suggested CACP syndrome. Due to excessive enteral protein losses, the patient was treated with Cotrimoxazol prophylaxis and immunoglobulin supplements. These supplements were inadequate to achieve normal IgG values. As constrictive pericarditis with subsequent PLE was the best explanation for the excessive IgG losses, pericardiectomy was performed with good results. Genetic testing in our patient was complicated but revealed a pathogenic mutation within the repeat sequence in exon 7 of the PRG4 gene. CONCLUSION: PLE resulting from constrictive pericarditis can be a complication of CACP syndrome. As serious complications can arise from the resulting secondary immunodeficiency, we recommend regular evaluation of clinical symptoms of constrictive pericarditis and PLE in children with CACP syndrome.

Spinal Cord Injury After Extremity Surgery in Children With Thoracic Kyphosis.

BACKGROUND: Spinal cord injury is a rare complication after lower extremity surgery in children with skeletal dysplasia and thoracic kyphosis. We encountered two patients who had this complication, from among 51 (39 from Nemours/Alfred I. duPont Hospital for Children and 12 from Seattle Children's Hospital) who underwent lower extremity surgery during an 8.5-year period (June 2004 to December 2012). Because spinal cord injury is a devastating complication likely not known to most physicians treating patients with skeletal dysplasias, we sought to examine factors that may contribute to this rare complication. CASE DESCRIPTION: We performed a retrospective review of two patients with skeletal dysplasia who had paraplegia develop after extremity surgery. Outcome measures included operative time, vital signs, and postsurgery recovery of neurologic deficit. MR images were reviewed. Two patients were found-an 8.5-year-old boy with spondyloepiphyseal dysplasia congenita with a 76°-thoracic kyphosis apex at T4 and a 6.5-year-old boy with mucopolysaccharidosis type 1-H with an 80°-thoracic kyphosis apex at T2. Bilateral proximal femoral osteotomies or bilateral innominate and proximal femoral osteotomies had been performed. The spinal cord injuries occurred at the apex of the kyphosis as determined by clinical examination and MRI assessment. In both patients, the mean arterial blood pressure decreased below 50 mm Hg and might be a factor in the etiology of the paralysis. The first patient recovered motor function in 5 months; the second had no recovery. LITERATURE REVIEW: Paraplegia is extremely rare after nonspine operations. Many factors contribute to the risk for a spinal cord event: low mean arterial pressure, duration of the surgery, position on the operating table, the kyphotic spine deformity, or unappreciated vascular disease. Motor-evoked potentials and somatosensory-evoked potentials together potentially provide high sensitivity and specificity for predicting a postoperative neurologic deficit. CLINICAL RELEVANCE: Based on our two patients with skeletal dysplasia and a literature review of patients with hyperkyphosis undergoing extremity surgery, the surgeon must be aware of the risk of spinal cord injury. Careful preoperative assessment possibly including MRI of the spine is recommended. Mean arterial pressure should be maintained at a safe level; neuromonitoring should be considered.

Acute, unstable slipped capital femoral epiphysis with associated congenital coxa vara.

Slipped capital femoral epiphysis in patients younger than 10 years is rare and is often associated with some identifiable metabolic or endocrinologic abnormality. We present a case of a 5-year-old girl with an acute, unstable, severe slipped capital femoral epiphysis associated with congenital coxa vara and its surgical management. This association has not been described in previous literature. Surgical treatment is proposed and described.

[How safe are orthoroentgenograms in determining the amount of correction for varus deformities?]. / Ortoröntgenogramlar varus diziliminin düzeltme miktari tespitinde ne kadar güvenilirdir?

OBJECTIVES: In this study, we evaluated the effects of the distance of the legs from the midline on alignment and angles of the lower extremities in orthoroentgenograms. PATIENTS AND METHODS: Between March 2012 and April 2013, 95 limbs of 56 patients with varus deformity who underwent orthoroentgenogram to identify the amount of joint laxity in two positions were included in this study. The initial X-ray was performed with the feet in contact, while the other was performed as the legs were abducted to be in line with the shoulders. For each orthoroentgenogram, the mean mechanical axis angle, anatomical axis, and joint line orientation angles were measured retrospectively. These measurements were repeated for 43 limbs with varus deformity >10°. RESULTS: In the orthoroentgenograms with the feet in contact, the mean mechanical axis angle was 9.58°±5.7°, (0.20°; 26.0°), the mean anatomical axis angle 3.65°±6.14°, (-9.0°; 21.0°), and the mean joint line orientation angle -3.41°±2.52°, (-12.0°; 1.60°). In the orthoroentgenograms with the legs abducted, the mean mechanical axis angle was 7.73°±5.58°, (-3.0°; 23.0°), the mean anatomical axis angle 2.62°±5.87°, (-11.0°; 18.30°), and mean joint line orientation angle was -2.44°±2.41°, (-13.0°; 3.0°). The differences in the angles between the two positions were statistically significant (p<0.005). CONCLUSION: Our study results showed that the mean values of mechanical axis angle, anatomical axis and the joint line orientation angle were higher in orthoroentgenograms with the feet in contact than the orthoroentgenograms with the legs abducted in patients with varus gonarthrosis. We suggest that this may lead to mistakes in the preoperative planning. Ideal positions should be standardized to minimize possible problems.

[Crooked legs- just an aesthetic problem]. / Krumme Beine - mehr als ein ästhetisches Problem?

Because the lower extremities are weight bearing, malalignment plays a key role in the development of degenerative disease of the joints. This is particularly true as degenerative arthropathy is of mechanical and not inflammatory cause. Deviation of the axis has been shown to alter the load and force distribution in the joint and thereby causing excessive wear. Whether or not a deformity is clinically relevant or not depends on the symptoms, the amount of the deformity and the location of the deformity. Relevant deformities can be treated with orthotics or corrective osteotomies in early stages. In late stages fusions or joint replacement is the mainstay of treatment.

Parce que les extrémités inférieures portent un poids, un mauvais alignement de ces dernières joue un rôle clé dans le développement des atteintes dégénératives des articulations. Cela est particulièrement vrai puisque l'arthropathie dégénérative est d'origine mécanique et non pas inflammatoire. Une déviation axiale a été montrée modifier la répartition des charges et des forces dans l'articulation et provoquer ainsi un poids excessif. Qu'une déformation soit significative ou non sur le plan clinique dépend des symptômes, de l'importance et de la localisation de la déformation. Les déformations significatives peuvent être traitées dans des stades précoces par des ostéotomies orthotiques ou correctrices. Dans les stades tardifs des fusions ou des remplacements articulaires représentent les options thérapeutiques principales.

Axial involvement with facet joint arthropathy and bony ankylosis in a case of camptodactyly, arthropathy, coxa vara, pericarditis (CACP) syndrome.

Familial arthropathy associated with congenital camptodactyly has been previously recognized as a definite clinical entity in the literature. The clinical spectrum of this disease seems to be variable. The typical features of congenital camptodactyly, arthropathy, coxa vara and pericarditis (CACP syndrome) appear to be a more frequent presentation in children from the Middle East and North Africa. Musculoskeletal presentation of this rare familial form of arthropathy is unique and heterogeneous. In all previous reports, non-inflammatory pattern of arthropathy involving the peripheral joints with typical coxa vara deformity were described, and in a few cases spine abnormalities, including kyphosis, lordosis, or scoliosis. We describe the first case of axial involvement in a typical case of CACP syndrome with facet joint arthropathy and ankylosis at L5/S1 levels.

[The UniSpacer™: correcting varus malalignment in medial gonarthrosis. Preliminary results]. / UniSpacer™: corrección de la desalineación en varo en la gonartrosis medial. Resultados preliminares.

While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA), or high tibial osteotomy (HTO), so far there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a modern, self-centering, metallic interpositional device for the knee. This study evaluates whether alignment correction can be achieved by UniSpacer™ arthroplasty as well as alignment change in the first 5 postoperative years is evaluated. Antero-posterior long leg stance radiographs of 15 legs were digitally analyzed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analyzed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analyzing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7±1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation.

Knee malalignment is associated with an increased risk for incident and enlarging bone marrow lesions in the more loaded compartments: the MOST study.

OBJECTIVE: To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs. METHODS: Subjects from the Multicenter Osteoarthritis Study aged 50-79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees (n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form 'more loaded' compartment, while lateral compartment in valgus and medial compartment in varus were combined to form 'less loaded' compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline. RESULTS: Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment [adjusted RRs (95%CI): 1.5 (1.2-1.9)] and valgus alignment in the lateral compartment [1.4 (1.0-2.1)]. Increase in BML score was more likely in the more loaded compartments [1.7 (1.4-2.0)] in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees [0.8 (0.7-1.0)]. CONCLUSION: Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.

Better outcomes in severe and morbid obese patients (BMI > 35 kg/m2) in primary Endo-Model rotating-hinge total knee arthroplasty.

The Endo-Model rotating-hinge prosthesis is preferably indicated as a primary implant in patients with advanced axial deviation of the lower limbs or unstable knees with severe bone defects. Outcomes were studied in 111 knees, operated in a three-year period; the mean followup was 28 months. Joint balance enhancement and limbs mechanical axis correction were achieved after surgery. There were 6 deep infections and 16 patients referred postoperative anterior knee pain. WOMAC index scores disaggregated by gender and BMI showed better outcomes in obese patients (specifically, those with a BMI of 35-40 kg/m(2)) and in men. Although the lack of a control group did not allow definite conclusions and despite a nonnegligible complication rate, our results reveal that the Endo-Model total knee arthroplasty can be a useful tool to deal with severe and morbid obese patients affected of severe gonarthrosis associated with marked axial deviations, ligament instability, or bone defects.

Simultaneous proximal femoral rotational and distal femoral varus osteotomies for femoral retroversion and genu valgum.

Whereas excess femoral anteversion and its related symptoms have been described many times, excess femoral retroversion is less well documented. We report the case of a 30-year-old woman who had a history of chronic bilateral hip and knee pain and evidence of excess femoral retroversion, genu valgum, early-onset lateral and patellofemoral compartment osteoarthritis of both knees, and hip arthritis. She experienced symptomatic relief after undergoing staged bilateral simultaneous proximal femoral rotational and distal femoral lateral opening wedge osteotomies. Although this combination of alignment problems is not an infrequent clinical occurrence, we have found no literature on this condition or treatment. The patient provided written informed consent for print and electronic publication of this case report.

Total hip arthroplasty in adolescents with severe hip arthropathy and dysplasia associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare disorder. Patients with this syndrome experience early symptomatic arthropathy of the hips. We report a case of adolescent siblings with bilateral arthropathy associated with CACP syndrome in which total hip arthroplasty was performed as treatment of severe associated disability. Postoperative Harris Hip Scores for patient 1 were 86 for the right at 18 months and 96 for the left at 12 months. Postoperative Harris Hip Score at 6 months for patient 2 was 53; however, he had good range of motion and lacked deformity. Based on our limited experience and the limited available clinical data, we feel that total hip arthroplasty is a reasonable treatment option for adolescents with debilitating hip arthropathy associated with CACP syndrome.

Clinical outcomes after arthroscopic psoas lengthening: the effect of femoral version.

PURPOSE: The purpose of this study was to examine the association between femoral anteversion and clinical outcomes after arthroscopic lengthening of a symptomatic, snapping psoas tendon in young patients. METHODS: Sixty-seven consecutive patients with symptomatic coxa saltans underwent arthroscopic psoas tendon lengthening through a transcapsular approach during a 3-year period by a single arthroscopic hip surgeon. Demographic and clinical variables were collected. Patients were divided into low/normal femoral version and high femoral version groups and analyzed for association of femoral version with clinical outcomes as measured by the modified Harris Hip Score (mHHS) and Hip Outcome Score (HOS) preoperatively and postoperatively with a minimum of 6 months' follow-up (range, 6 to 24 months). Two-sample t tests were used for data analysis, with P < .05 defined as significant. RESULTS: Preoperative evaluation showed excessive anteversion (>25°) associated with worse HOS sports subscale scores (26.6 v 50.0 for excessive v low/normal anteversion, P = .013) and no difference in mHHS and HOS activities-of-daily living subscale scores. Postoperative mHHS scores were significantly different (76.9 v 86.1 for excessive v low/normal anteversion, P = .031). No association was noted between clinical outcome measures and any other clinical or demographic variable (P > .05). CONCLUSIONS: Patients with increased femoral anteversion may be at greater risk for inferior clinical outcomes after arthroscopic lengthening of a symptomatic, snapping psoas tendon. The psoas tendon may be an important passive and dynamic stabilizer of the hip in these patients, and release may result in a greater alteration of kinematics with high-demand activities, particularly terminal extension and external rotation when the tendon is typically at its highest tension. These results may help surgeons identify which patients may be at risk for inferior clinical outcome after psoas lengthening.

Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol.

BACKGROUND: Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people, giving rise to pain and loss of function. Many people experience progressive worsening of the disease over time, particularly those with varus malalignment and increased medial knee joint load. Therefore, interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression. Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load. A neuromuscular exercise program, emphasising optimal alignment of the trunk and lower limb joints relative to one another, as well as quality of movement performance, while dynamically and functionally strengthening the lower limb muscles, may be able to reduce medial knee load. Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature. This randomised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading, pain and function in individuals with medial knee joint osteoarthritis. We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program. METHODS/DESIGN: 100 people with medial knee pain, radiographic medial compartment osteoarthritis and varus malalignment will be recruited and randomly allocated to one of two 12-week exercise programs: quadriceps strengthening or neuromuscular exercise. Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home. The primary outcomes are medial knee load during walking (the peak external knee adduction moment from 3D gait analysis), pain, and self-reported physical function measured at baseline and immediately following the program. Secondary outcomes include the external knee adduction moment angular impulse, electromyographic muscle activation patterns, knee and hip muscle strength, balance, functional ability, and quality-of-life. DISCUSSION: The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load, pain and physical function in people with medial knee osteoarthritis and varus malalignment. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN12610000660088.