Legg-Calvé-Perthes disease (LCPD) is a syndrome of idiopathic avascular necrosis of the proximal femoral head in children resulting from compromise of the blood supply to the developing capital femoral epiphysis .1 It is one of the most common causes of permanent femoral head deformity in children. 2
The cause of the disease is multifactorial involving both genetic and environmental factors. Genetic factors may contribute to the susceptibility of vascular compromise to the capital femoral epiphysis. 2 Polymorphisms in the endothelial nitric oxide synthase gene (eNOS) has been identified in patients with LCPD. 3 Environmental factors include mechanical overload causing repeated subclinical trauma and maternal smoking. Patients often have delayed bone age. 2
Epidemiology including risk factors and primary prevention
The disease affects children between ages 2 and 14 with a peak incidence between ages 4 and 8. LCPD is a rare, afflicting 1 in 1200 children.4 The male to female ratio is 4 to 5:1; most commonly unilateral with 10-15% of cases are bilateral. The disease is much more common in Caucasian children than in Asians or African Americans. There is a significant geographic variation among countries. Equatorial regions have a low incidence of the disease, whereas Northern Europe has the highest documented incidence.5 Risk factors include exposure to secondhand smoke, hyperactive behavior, and children small for their age.
Pathophysiology of LCPD remains unclear, but the following processes are generally accepted:
- Blood supply to the femoral head is interrupted due to vulnerability to mechanical compression. The lateral epiphyseal artery disruption at its origin is demonstrated in 68% of patients in all stage of the disease. 2
- Bone infarction and necrosis affect the subchondral bone, articular cartilage, and bone epiphysis.
- Revascularization occurs and new bone ossification starts. Some patients may have healthy bone growth and development.
- With progression of the disease, bone resorption, delayed bone formation, invasion of fibrovascular tissue and subchondral fractures occur. Ischemic necrosis is also associated with increased calcium content of the necrotic bone, which is thought to make bone more brittle and prone to microdamage from normalphysical activity.
- This may result in deformities in the femoral head and epiphyseal growth plate.2,4
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
LCPD can be divided into 4 stages (with subgroups) based on the modified Waldenstrom radiographic classification, which has high inter-and intra-rater reliability. 6 Determinates of the duration of each stage and total duration of the active phase is unknown, but older patients appear to have a longer duration than younger patients.
|I: Initial phase- 6 months|
|Intermittent synovitis with pain, limp, and irritability of the hip.7 Symptoms increase with activity and diminish with rest.||IA: All/part of epiphysis is sclerotic without loss of epiphyseal height|
IB: Epiphysis is sclerotic with loss of epiphyseal height
|II: Fragmentation phase- 8 months|
|More definite loss of hip internal rotation and abduction.||IIA: Beginning to fragment, 1-2 vertical fissures|
IIB: Advanced fragmentation
Without new bone formation lateral to epiphyseal fragments
|III: Re-ossification phase- 3-5 years|
|Patients gradually improves, and after 2 years are usually back to normal activity with little complaints.||IIIA: Early new bone formation lateral to fragmentation; Abnormal texture (porotic)|
New bone < 1/3 width of epiphysis
IIIB: New bone >1/3 width of epiphysis; Normal texture
|IV: Residual phase-many years|
|No change in bone density|
Final epiphyseal shape established
Acetabular remodeling seen
Specific secondary or associated conditions and complications
Permanent femoral head deformity in LCPD predisposes children to early onset and/or more severe course of osteoarthritis of the hip, as well as leg length discrepancy.8 By the 6th decade, 50% of untreated patients will develop disabling osteoarthritis requiring a hip replacement.9
2. ESSENTIALS OF ASSESSMENT
A detailed history should include the location, onset, duration, quality, radiation of pain, child activity level and any exacerbating or alleviating factors. Typically, the parents reports that the child limps and complains of occasional groin, thigh or knee pain.
Exam both lower extremities to identify bilateral LCPD.
- Atrophy of quadriceps and adjacent thigh soft tissues (can measure thigh girth to determine atrophy).
- Limited hip range of motion, especially internal rotation and abduction.
- Pain with passive hip range of motion.
- Leg length discrepancy.
- Antalgic or trendelenburg gait (pain in the gluteus medius muscle or hip).
There are no established scales for functional assessment in LCPD. Due to pain and/or range of motion limitations, the child may exhibit impairment in walking, running, jumping, climbing stairs, or stooping for long periods of time. 8
When the diagnosis is unclear, initial laboratory studies can aid in ruling out other diagnoses. Complete blood count, erythrocyte sedimentation rate, and C-reactive protein may be helpful to rule out infection. These studies will be normal in LCPD.
The mainstay imaging study for the diagnosis and surveillance of LCPD is an anterior-posterior and lateral pelvis radiograph. It is important to assess the integrity and shape of the femoral head using above mentioned four stages classification. 8 If early film is negative and the symptoms are very recent, the radiograph should be repeated in one month.7
Other studies include:
- Dynamic contrast enhanced subtraction MRI : more sensitive than radiography, correlate well with bone scintigraphy, better delineate blood flow to the femoral head for early ischemia detection; provide a prognostic value with physeal involvement. 2
- Ultrasound- low risk, cost effective, however non-specific. May help rule out synovitis of the hip. 10
Early predictions of outcomes
There are several classifications used to prognosticate outcome:
- Catterall: a 4 category system that emphasizes the extent of femoral head involvement and outcome. The Catterall groups I, II, III, and IV represent 25%, 50%, 75%, and total head involvement, respectively.9
- Salter-Thomson: simplifies to 2 groups. Group A (Catterall I and II) infers that less than 50% of the ball is involved, and group B (Catterall III and IV), that more than 50% of the ball is involved.9
In both of these classifications, if less than 50% of the ball is involved than the prognosis is good, whereas if more than 50% is involved, a potentially poor prognosis is indicated6 (i.e., early degenerative arthritis).
Other predictors of outcome:
- Shape of the femoral head at the time when disease heals is an important determinant of the risk of degenerative arthritis.9If the femoral head is spherical when the disease heals, it is likely that degenerative arthritis will not develop.11
- Age of onset9
- Before6 years of age: there is a better prognosis possibly due to longer time period for , revascularization and remodeling of the femoral head.
- After 8 years old: more likely to have poor prognosis with significant symptoms, restricted range of motion (ROM), and early degenerative arthritis.
- Clinical features such as girls, heavy patients, stiff hip with adduction contracture and a longer duration from onset to healing phase, have been associated with a poor prognosis. 2
Practitioners should obtain information about stairs and level of floors in the household because these can be architectural barriers to patients with impaired mobility or weight bearing restrictions.
If not treated , patients can have uncontrolled pain and impaired mobility that can limit quality of life or interfere with school functioning. A missed diagnosis can also lead to osteonecrosis of the femoral head; and a risk of legal action due to lost treatment opportunity.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Available or current treatment guidelines
There are evidence-based care guidelines concerning post-operative management and conservative treatment of LCPD in children for age 3 to 12. These guidelines are mostly based on ‘local consensus’ of the LCPD team from Cincinnati Children’s Hospital Medical Center. 12
At different disease stages
There is general consensus that the age of the child at the onset of symptoms, the extent of femoral head involvement, stage of the disease and the presence of the femoral head extrusion must be considered when deciding the best treatment options. 2Children with mild disease are able to heal and recover fully without treatment.
Treatment is aimed at minimizing damage, not curing the disease. Physical therapy (PT) can produce improvement in articular range of motion, muscular strength and articular dysfunction. 13 Active treatment is advised when there is at least 50% of epiphyseal involvement.14 Generally, patients with Catterall classifications I or II can be treated conservatively, whereas classifications III or IV often require surgical intervention. The short-term goal is reduction of pain and stiffness of the hip. The principal of treatment is containment of the femoral head within the spherical acetabulumto allow spherical re-ossification.Nonsurgical Treatment:
- Supervised physical therapy is supplemented with a customized home exercise program..13
- Abduction orthosis and casting may be helpful, however, the current evidence in the literature does not support the use of orthoses. 2
- Restriction of activity helps relieve pain. Crutches/nonweight bearing are used if symptoms are severe.15Swimming is recommended, and running-based sports should be avoided.
- Nonsteroidal anti-inflammatory drugs should be used for acute pain and inflammation.
- Additional studies are needed to establish the efficacy of treatment including extracorporeal shock wave therapy, pulsed electromagnetic fields and hyperbaric oxygen in LCPD children. 16,17,18
- Femoral varus osteotomy and pelvic osteotomy may achieve better containment of the femoral head with modest treatment effect.2
- In the late stage, a valgus femoral osteotomy overcomes the hinging and bring a more congruent surface of femoral head under the acetablulum. 2
- Arthrodiastasis (distraction of a joint) provides unloading of the hip joint.
- Total hip replacement may be needed later in life if severe osteoarthritis develops.
Coordination of care
A multidisciplinary team includes physiatry, PT, occupational therapy, and orthopedics. The physiatrist plays a role in monitoring symptoms, prescribing PT and pain medications, obtaining radiographs, determining weight-bearing status, and referral to a pediatric orthopedist. It is important that all patients establish care with team to determine treatment options. Follow-up visits focus on symptoms, hip mobility, and disease progression.
Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based.
The Iowa Hip Score and Nonarthritic Hip Score are used in addition to the Stulberg classification to evaluate functional outcomes in LCPD.19
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Surgery may eliminate longer-term bracing and allow earlier resumption of activities. The prognosis is better with early detection (under the age of 8 years).Patients older than 9 years of age at onset with Catterall classifications of III and IV have unpredictable success rates, regardless of treatment.15
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
Cutting edge concepts and practice
Antiresorptive agents may provide useful adjunctive therapy. Animal studies of ischemic osteonecrosis of hip indicated that combined treatment of bone morphogenetic protein (BMP)-2 with bisphosphonates can decrease bone resorption, increased new bone formation and preserve the femoral head shape. 2,20
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
Lack of basic science studies to understand the causative factors, the nature of the vascular events and the intricate events of bone and cartilage damage, particle removal and eventual repair.
There are needs for well designed, controlled studies to explore new treatment options for advanced LCPD, since neither conservative nor operative management showed desirable outcomes.
In addition, antiresorptive and anabolic agents need further investigation to assess their clinical efficacy in the treatment of LCP disease. 20
- Pinheiro, M., & Dobson, C. A. New insights into the biomechanics of Legg-Calvé-Perthes’ disease. Bone and Joint Research 2018;7:2, 148-156.
- Ibrahim T, Little DG. The Pathogenesis and Treatment of Legg-Calvé-Perthes Disease. JBJS Rev. 2016 Jul 19;4(7).
- Ding, X. Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease. Experimental and Therapeutic Medicine 2016;11:5, 1913–1917.
- Hernandez J. Legg-Calve-Perthes disease in emergency medicine [Medscape Web site]. Available at: http://emedicine.medscape.com/article/826935. Accessed April 27, 2013.
- Perry DC, Hall AJ. The epidemiology and etiology of Perthes disease. Orthop Clin N Am2011;32:279-283.
- Hyman, J. E., Trupia, E. P., & Wright, M. L. Interobserver and intraobserver reliability of the modified Waldenström classification system for staging of Legg-Calvé-Perthes disease. Journal of Bone and Joint Surgery American Volume 2015;97:8, 643-650.
- Herring, JA, Legg-Calve-Perth disease. In: Staheli LT, Song, KM, Pediatric Orthopaedic Secrets.Philadelphia, PA: Elsevier; 2007: 349-352.
- Rampal, V., Clement, J. L., & Solla, F. Legg Calve Perthes Disease: classification and prognostic factors. Clinical Cases in Mineral and Bone Metabolism 2017;14:1, 74-82.
- Kim H, Herring JA. Pathophsysiology, classifications, and natural history of Perthes disease. Orthop Clin N Am 2011;42:285-295.
- Dimeglio A, Canavese F. Imaging in Legg-Calvé-Perthes disease. Orthop Clin North Am2011;42:297-302.
- Wenger DR, Hosalkar HS. Principles of treating the sequelae of Perthes disease. Orthop Clin N Am. 2011;42:365-372.
- Brecht GC, Guarnieiro R. Evaluation of physiotherapy in the treatment of Legg-Calvé-Perthes disaese. Clinics 2006;61(6):521-528
- Wheeless CR III. Legg Calve Perth disease. Available at: http://www.wheelessonline.com/ortho/legg_calve_perthes_disease. Accessed April 27, 2013.
- Murphy KP, Wunderlich CA. Orthopedics and musculoskeletal conditions. In: Alexander MA, Matthews DJ, editors,Pediatric Rehabilitation: Principles and Practice. 5th edition. New York, NY: Demos Medical Publishing 2015:241-242.
- Wang CJ, et al. Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting. J Bone Joint Surg Am. 2005; 87:2380.]
- Massari L, et al. Biophysical stimulation with pulsed electromagnetic fields in osteonecrosis of femoral hed. J Bone Joint Surg Am. 2006; 88 suppl 3:56.
- Camporesi EM, et al. Hyperbaric oxygen therapy in femoral head necrosis. J Arthroplasty. 2010; 25: 118.
- Larson AN, Sucato DJ, Herring JA, et al. A prospective multicenter study of Legg-Calvé-Perthes disease: functional and radiographic outcomes of nonoperative treatment at a mean follow-up of twenty years. J Bone Joint Surg Am2012;94:584-592.
- Little DG, Kim HK. Potential for bisphosphonate treatment in Legg-Calve-Perthes disease [abstract]. J Pediatr Orthop2011;31(2 Suppl):S182-S188.
Joseph B. Prognostic factors and outcome measures in Perthes disease. Orthop Clin N Am 2011;42:303-315.
Novais ED, Clohisy J, Siebenrock K. Treatment of symptomatic healed Perthes hip. Orthop Clin N Am 2011;42;401-417.
Original Version of the Topic
Rajashree Srinivasan, MD, Anwar Zaman, MD.
Yuxi Chen, MD
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Ashley Kakkanatt, MD
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Jinpu Li, MD
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