Legg-Calve-Perthes Disease

Disease/ Disorder

Definition

Legg-Calvé-Perthes disease (LCPD) is a syndrome of unilateral or bilateral idiopathic avascular necrosis of the proximal femoral head (FH) 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

Etiology

The cause of the disease is multifactorial involving both genetic, environmental, and nutritional 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 LCPD has a higher incidence in groups of lower socioeconomic status, indicating nutritional support may play a role.⁴

Epidemiology including risk factors and primary prevention

The disease affects children between ages 3 and 12 with a peak incidence between ages 5 and 7. LCPD is a rare, afflicting 1 in 1200 children.⁴ The male to female ratio is 4 to 5:1; most commonly unilateral with 10-24% of cases are bilateral. The disease is much more common in Caucasian children with declining incidence in Asian and African American populations.⁴ 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.

Patho-anatomy/physiology

Pathophysiology of LCPD remains unclear, but the following processes are generally accepted:

• Blood supply to the FH 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 normal physical activity.
• This may result in deformities in the FH 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 four 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.

Stage	Features	Radiographic findings
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 Without fragmentation
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

Essentials of Assessment

History

A detailed history should include the onset, duration, quality, location, radiation of pain, exacerbating or alleviating factors, and child’s activity level. The child often participates in high impact sports, has smoke exposure, or deprivation.⁴ Typically, the parents report that the child complains of occasional groin, thigh or knee pain, and limps.

Physical examination

Examine both lower extremities to identify bilateral LCPD.

Observe for:

• Atrophy of quadriceps and adjacent thigh soft tissues (can measure thigh girth to determine atrophy).
• Limited hip range of motion, especially internal rotation, extension and abduction.
• Pain with passive hip range of motion.
• Leg length discrepancy.
• Antalgic or trendelenburg gait (pain in the gluteus medius muscle or hip).

Functional assessment

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

Laboratory studies

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.

Imaging

The 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 FH using the above-mentioned four stages.⁸ If early film is negative and the symptoms are recent, the radiograph should be repeated in one month.⁷ The gold standard is dynamic contrast enhanced subtraction MRI as it better delineates blood flow to the FH for early ischemia detection, correlates well with bone scintigraphy, provides prognostic value with physeal involvement and is more sensitive than radiography.^2,4

Other studies include:

• Computed tomography scanning can reveal zones of osteosclerosis but is non-specific.⁴
• Ultrasound is low risk and 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 FH involvement and outcome. The Catterall groups I, II, III, and IV represent 25%, 50%, 75%, and complete head involvement, respectively.⁹
• Salter-Thomson: simplifies to 2 groups. Group A (Catterall I and II) infers that less than 50% of the FH is involved, and group B (Catterall III and IV), that more than 50% of the ball is involved.⁹

In both classifications, if less than 50% of the FHis involved then the prognosis is good, whereas if more than 50% is involved, a potentially poor prognosis is indicated ⁶ (i.e., early degenerative arthritis).

• Herring: is based on the height of the lateral pillar of the FH epiphysis in the fragmentation period of the disease and is divided into three groups. Group A: no involvement of the lateral pillar; Group B: lateral pillar height loss < 50%; and group C: height loss > 50%. The predictive value of the Herring classification is higher in the early stages of the disease.⁹

Other predictors of outcome:

• The shape of the FH at the time of healing is a determinant for the risk of degenerative arthritis.⁹ If the FH is spherical when the disease heals, it is likely that degenerative arthritis will not develop.¹¹
• Age of onset⁹
  • Before 6 years old:  There is a better prognosis possibly due to longer time periods for revascularization and remodeling of the FH.
  • After 8 years old: higher chance of poor prognosis with significant symptoms, including 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

Environmental

Practitioners should obtain information about the household number of stairs and levels, because these can be architectural barriers to patients with impaired mobility or weight bearing restrictions.

Professional Issues

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 FH; and a risk of legal action due to lost treatment opportunity.

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 FH involvement, stage of the disease and the presence of the FH 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. The goal is to prevent FH deformity, early onset cox-arthrosis, and to delay disparity between affected and unaffected hip.⁴ Physical therapy (PT) can produce improvement in articular range of motion, dysfunction and muscular strength.¹³ Generally, patients with Catterall classifications I or II can be treated conservatively, whereas Catterall 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 acetabulum to allow spherical re-ossification.

Nonsurgical Treatment:

• Restriction of activity with rest for 5-7 days is recommended for 5 to 7 days to relieve hip pain or stiffness.⁴ Crutches/non-weight bearing are used if symptoms are severe.¹⁴Swimming is recommended and running-based sports should be avoided.
• Nonsteroidal anti-inflammatory drugs should be used for acute pain and inflammation.
• Orthosis with progressive hip abduction for 7 to 10 days and casting to immerse the femoral head into the coxal cavity may be helpful, which is followed by arthrography if the joint fails to mobilize.^4,15
• Supervised physical therapy is supplemented with a customized home exercise program.¹³ Partial weight-bearing with crutches can begin with improvement in pain and full ROM through the hip.¹⁴
• Additional studies are needed to establish the efficacy of modalities to increase femoral head strength or improve blood supply such as balneotherapy, glycosaminoglicans, bisphosphonates, plasma therapy,²³ extracorporeal shock wave therapy, pulsed electromagnetic fields, and hyperbaric oxygen in LCPD children.^15,1,17,18
• No robust evidence was found from non-randomized studies regarding the most effective non-surgical interventions for LCPD children.¹⁵

Surgical Treatment:

• If FH deformity prevents hip abduction due to a contracture, percutaneous hip adductor release may be performed followed by containment therapy once the joint has been maximally abducted.¹⁹ Femoral varus osteotomy and pelvic osteotomy may achieve be6tter containment of the femoral head with modest treatment effect.
• In the late stage in children of 8 years older, the recommended shelf arthroplasty is considered a salvage procedure as it can cause hip incongruency in order to preserve acetabular coverage.^19,20A valgus femoral osteotomy overcomes the hinging and bring a more congruent surface of femoral head under the acetabulum.² It is indicated for those with active disease with non-containable hips or recovered disease with painful hinge abduction .¹⁹
• Arthrodiastasis (distraction of a joint) provides unloading of the hip joint.
• Skeletally mature individuals are candidates for cheilectomy, which only corrects FH deformities.¹⁹
• 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 a 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.²¹

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. Operative and nonoperative treatments had comparable rates of good outcome of about 77%. The prognosis is better with early detection (under the age of 8 years).^14,19 Patients younger than 6 years had better outcome with nonoperative than with operative, whereas the opposite was true for children over 6 years of age.²⁰ When choosing operation, this younger population tends to have a slightly better outcome with pelvic rather than femoral osteotomy. Varying reports give conflicting results on prognosis between genders with some showing females with worse prognosis and some with no gender differences. Bilateral cases tend to have poorer prognosis.¹⁹

Cutting Edge/ Emerging and Unique 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, increase new bone formation and preserve the femoral head shape.^2,22 In addition, treatment with Strontium ranelate in rat models has shown prevention in collapse of the ischemic FH and enhanced trabecular thickness.²³

Gaps in the Evidence-Based Knowledge

Lack of basic science studies to understand the causative factors, nature of vascular changes, intricate events of bone and cartilage damage, and particle removal and eventual repair.

There is a need 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.²²

References

1. Pinheiro, M., & Dobson, C. A. New insights into the biomechanics of Legg-Calvé-Perthes’ disease. Bone and Joint Research 2018;7:2, 148-156.
2. Ibrahim T, Little DG. The Pathogenesis and Treatment of Legg-Calvé-Perthes Disease. JBJS Rev. 2016 Jul 19;4(7).
3. Ding, X. Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease. Experimental and Therapeutic Medicine 2016;11:5, 1913–1917.
4. Rodriguez-Olivas A, et al. Legg-Calve-Perthes disease overview. Orphanet Journal of Rare Diseases 2022; 17:125.
5. Perry DC, Hall AJ. The epidemiology and etiology of Perthes disease. Orthop Clin N Am2011;32:279-283.
6. 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.
7. Herring, JA, Legg-Calve-Perth disease. In: Staheli LT, Song, KM, Pediatric Orthopaedic Secrets.Philadelphia, PA: Elsevier; 2007: 349-352.
8. 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.
9. Kim H, Herring JA. Pathophsysiology, classifications, and natural history of Perthes disease. Orthop Clin N Am 2011;42:285-295.
10. Dimeglio A, Canavese F. Imaging in Legg-Calvé-Perthes disease. Orthop Clin North Am2011;42:297-302.
11. Wenger DR, Hosalkar HS. Principles of treating the sequelae of Perthes disease. Orthop Clin N Am. 2011;42:365-372.
12. https://www.physio-pedia.com/Legg-Calve-Perthes Disease
13. Brecht GC, Guarnieiro R. Evaluation of physiotherapy in the treatment of Legg-Calvé-Perthes disaese. Clinics 2006;61(6):521-528
14. Murphy KP, et al, . Musculoskeletal conditions. In: Alexander MA, Matthews DJ, editors,Pediatric Rehabilitation: Principles and Practice. 6th edition. New York, NY: Demos Medical Publishing 2021:380-382.
15. Galloway AM, van-Hille T, Perry DC, Holton C, Mason L, Richards S, Siddle HJ, Comer C. A systematic review of the non-surgical treatment of Perthes’ disease. Bone Jt Open. 2020 Dec 2;1(12):720-730.
16. 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.]
17. 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.
18. Camporesi EM, et al. Hyperbaric oxygen therapy in femoral head necrosis. J Arthroplasty. 2010; 25: 118.
19. Bralto M et al. Global differences in the treatment of Legg-Calve-Perthes disease: a comprehensive review. Archives of Orthopaedic and Trauma Surgery 2021; 141: 1-16
20. Tukitiyeva N et al. Methods of treatment of Legg-Calve-Perthes Disease (Review). Georgian Med News 2021; (313):127-134.
21. 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 Am 2012;94:584-592.
22. Little DG, Kim HK. Potential for bisphosphonate treatment in Legg-Calve-Perthes disease [abstract]. J Pediatr Orthop2011;31(2 Suppl):S182-S188
23. Chen, YP., Tan, A., Ho, WP. et al. Effectiveness of Strontium Ranelate in the Treatment of Rat Model of Legg–Calve–Perthes Disease. IJOO 52, 380–386 (2018).

Bibliography

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. Legg Calve Perthe Disease. 1/30/2014

Previous Revision(s) of the Topic

Yuxi Chen, MD, Ashley Kakkanatt, MD, and Jinpu Li, MD. Legg Calve Perthe Disease. 6/26/2018

Author Disclosure

Yuxi Chen, MD
Nothing to Disclose

Marjorie Morales, MD
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Emilee Bell, DO
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Mihir Jani, MD
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