NORD gratefully acknowledges Young-Jo Kim, MD, PhD, Director, Child and Young Adult Hip Preservation Program, Director, Pediatric Orthopedic Fellowship, Professor of Orthopedic Surgery, Harvard Medical School, for his assistance in updating this report.
Legg-Calvé-Perthes disease (LCPD) is one of a group of disorders known as the osteochondroses. The osteochondroses typically are characterized by degeneration and subsequent regeneration of the growing end of a bone (epiphyses). In LCPD, the growing end of the upper portion of the thigh bone (femur) is affected. The upper section of the thigh bone is known as the head or “the ball” and connects to the hip in a depression or “socket”. This is the hip joint, which is a ball and socket joint. The disorder results from an unexplained interruption of the blood supply (ischemia) to the head of the femur, which causes degeneration (avascular necrosis) and deformity of the femoral head. Symptoms may include a limp with or without pain in the hip, knee, thigh, and/or groin; muscle spasms; and/or limited or restricted movement of the affected hip. The disease process seems to be self-limiting as new blood supplies are established (revascularization) and new healthy bone forms (re-ossifies) in the affected area. The exact cause for the temporary interruption of blood flow to the femoral epiphysis is not fully understood. Most cases appear to occur randomly for no apparent reason (sporadically).
The age of onset, severity, duration, and associated complications of Legg-Calvé-Perthes disease vary greatly from one person to another. Generally, the onset is slow and the progression is gradual. The disorder usually affects children between the ages of eight and ten years, with some instances occurring as early as age two or as late as age 12. The disease typically affects one leg (unilateral); however, in approximately 10% of cases, the condition may subsequently develop in the other leg (bilateral).
In most children, the first symptom is a limp with or without pain. Affected children may experience pain in the hip, knee, thigh, and/or groin. In some cases, the pain may be limited (localized) to the knee or inner part of the thigh. In addition, affected children may also experience muscle spasms of the legs; loss of muscle mass (atrophy) of the front thigh muscles; limited or restricted movements of the hips; and/or inflammation of the membrane lining the hip joint (synovitis). As affected children age, they may also exhibit slightly differing lengths of their two legs (leg length discrepancy).
In all cases, blood supply to the capital femoral epiphysis is re-established and degenerative (necrotic) bone is resorbed and rehardens (re-ossifies). This occurs without therapeutic intervention (spontaneously). The regenerated bone may be only slightly abnormal, misshapen, or significantly misshapen (e.g., abnormally flattened or unusually enlarged). In almost all cases, some shortening of the leg occurs, and in more severe cases, the femoral head may be deformed. The length of time between onset of LCPD and new bone formation may be as short as 18 months or as long as four years.
When onset occurs during the ages of four to nine years, it is, depending on treatment, less likely that osteoarthritis will develop later in life than it is in children with onset after the age of 10. Affected individuals who present significant deformity during re-ossification of the capital femoral epiphysis have an increased risk of developing osteoarthritis later in life.
The symptoms of Legg-Calvé-Perthes disease develop due to damage to the growing portion (epiphysis) of the upper end of the thigh bone. This damage results from interruption of the blood supply (ischemia) to this region. This damages the bone-forming cells (osteoblasts) and resident bone cells (osteocytes) and results in degeneration (necrosis) and softening of the bone in this area. The upper end of thigh bone becomes fragile as bone mass is lost. It is possible that this fragile area may “fracture” internally, causing deformity. A thin line of decreased density (Caffey sign) may be apparent on the epiphysis, which may represent such a “fracture” within the bone (subchondral). Damaged bone may fragment and cause irregularities when blood flow to the affected area eventually resumes (revascularization). As the bone regrows and rehardens (re-ossifies), it may deform, resulting in permanent malformation of the upper thigh bone (e.g., abnormally flattened or unusually enlarged epiphysis).
The exact, underlying cause of the interrupted blood flow is not fully understood. Multiple factors including environmental and genetic ones may play a role in the development of the disorder. Some risk factors or conditions that may play a role in the development of LCPD include low birth weight, delayed skeletal maturity, trauma, adverse social and economic conditions, exposure to tobacco smoke, or a positive family history of the disorder. Some researchers have theorized that disorders that disrupt or affect how the blood clots (coagulation disorders) such as thrombophilia play a role in some individuals. These disorders could lead to abnormal blood clot formation would cause the interrupted blood flow that characterizes LCPD.
No one theory has been proven as the underlying or contributing cause(s) of LCPD and it is possible that different individuals may have a different underlying causes. More research is necessary to determine the complex interactions that ultimately bring about the disorder.
In a handful of extremely rare familial instances, mutations in the COL2A1 gene have been linked to avascular necrosis of the head of the thigh bone in children.
Legg-Calvé-Perthes disease affects males approximately four to five times as often as females (4-5:1). According to reports in the medical literature, when the disorder occurs sporadically, males are predominantly affected. However, in families with more than one affected member (kindreds), the disorder appears to occur relatively equally among males and females. Reported cases of LCPD include several individuals within multiple, multigenerational families.
The disorder usually affects children between the ages of six and 10 years; however, associated symptoms and findings may become apparent as early as age two or as late as age 12. The incidence and prevalence of LCPD is unknown and estimates vary greatly from one country to another. The disorder is more common in Caucasians.
In most children with Legg-Calvé-Perthes disease, the first sign is a limp with or without pain in the hip, knee, thigh, or groin. Ordinary x-rays (radiograms) are almost always diagnostic. The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests, such as magnetic resonance imaging (MRI), arthrography, scintigraphy, and/or sonography.
During MRI, a magnetic field and radio waves are used to create cross-sectional images of the upper end of the thigh bone (capital femoral epiphysis) and may demonstrate abnormal development of the epiphyses. Arthrography, in which an opaque substance is injected into a joint before X-rays are taken, is especially helpful in showing the cartilage surface of the bone and its shape. The X-rays may help to determine the shape of the end of the bone where it joins (articulates) with the hip. Viability of the bone may be evaluated using a specialized technique known as bone scan. During a bone scan, the individual ingests a radioactive substance that will accumulate in the target area (e.g., bones). A specialized camera is then used to detect the levels of radioactivity present in these structures, producing an image of the targeted structure. In sonography, reflected sound waves create an image of certain tissues and body structures and may detect characteristic changes in the hip and femur, such as Caffey sign.
The treatment of Legg-Calvé-Perthes disease is directed toward the specific symptoms presented by each individual. Treatment varies with the severity of symptoms and may require the coordinated efforts of a team of specialists. Pediatricians usually refer patients to specialists who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); orthopedic surgeons, especially those that specialized in pediatrics; physical therapists; and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
Degenerative bone changes associated with LCPD usually heal on their own without intervention (spontaneously). Affected children should be closely monitored so the progression of the disease may be evaluated to ensure the bone reforms properly. Physical therapy may be recommended to maintain a good range of motion of the joint. Radiologic studies (e.g., MRI, arthrography, and bone scan) may be used to assist in monitoring the progression of the disease.
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can be used for mild to moderate pain.
In other cases, decreased physical activity, bedrest (if pain is present and prolonged) with or without traction, and/or stretching exercises (if stiffness occurs), particularly exercises in which the legs are rotated away from the body (abduction exercises), may be recommended to decrease pain in the hip and maintain proper mobility of the joint. In addition, as an affected child ages and regrowth of the epiphysis occurs, physicians must ensure that epiphyseal growth is contained within the cavity of the hip bone (acetabulum) where the thigh bone (femur) and hip normally meet (articulate).
Nonsurgical treatment may include crutches or a special brace or cast to keep the ball of the joint completely within the socket (acetabulum) so that it will not deform while healing.
Surgical treatments may include various procedures designed to place and keep the ball within the socket. Surgery is done mainly to improve and preserve the shape of the hip joint in order to prevent or reduce the chances of arthritis later during life. A femoral or pelvic osteotomy is often performed. Osteotomy is a surgical procedure in which bone is cut to shorten, lengthen, or change the alignment (i.e. reposition or reorient the bone). Some adults may ultimately require a total hip replacement surgery (total hip arthroplasty) later in life due to osteoarthritis.
Physicians may rely upon specific classification systems to make certain decisions concerning treatment and predict an affected individual’s long-term progress. For example, the Stulberg Classification System, created in 1981, defines five outcome categories based upon the shape of the femoral head and its relationship with the hip socket (as seen upon x-ray imaging studies). However, the variability of the disease and long term follow up needed to understand the outcome of treatment have contributed to the lack of establishing a universal treatment strategy for children with this disorder.
There has been some investigation into use a class of drugs known as bisphosphonates to treat individuals with Legg-Calvé-Perthes disease. These drugs slow or stop the natural process of bone loss, preventing the loss of bone mass and preserving increased bone density and strength. Initial reports have shown promise in the use of these drugs. However, more research, such as appropriate clinical trials, are needed to determine the long-term safety and effectiveness of such medications for the treatment of children with LCPD.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Legg-Calve-Perthes Disease (LCPD). In: Pediatric Orthopedics in Practice, 2nd ed. Hefti F, Brunner R, Freuler F, Hasler C, Jundt G, Krieg A, editors. 2015 Springer, Berlin, Germany. pp. 236-249.
Nochimson GF. Legg-Calve-Perthes Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:16.
Hyman JE, Trupia EP, Wright ML, et al. Interobserver and intraobserver reliability of the modified Waldenstrom classification system for staging of Legg-Calvé-Perthes disease. J Bone Joint Surg Am. 2015;97:643-650. http://www.ncbi.nlm.nih.gov/pubmed/25878308
Heesakkers N, van Kempen R, Feith R, Hendriks J, Schreurs W. The long-term prognosis of Legg-Calvé-Perthes disease: a historical prospective study with a median follow-up of forty one years. Int Orthop. 2015;39:859-863. http://www.ncbi.nlm.nih.gov/pubmed/25408489
Georgiadis AG, Seeley MA, Yelling JL, Sankar WN. The presentation of Legg-Calvé-Perthes disease in females. J Child Orthop. 2015;9:243-247. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549350/
Seufert CR, McGrory BJ. Treatment of arthritis associated with Legg-Calvé-Perthes disease with modular total hip arthroplasty. J Arthroplasty. 2015;30:1743-1746. http://www.ncbi.nlm.nih.gov/pubmed/25979188
Kannu P, Howard A. Perthes’ disease. BMJ. 2014;349:g5584. http://www.ncbi.nlm.nih.gov/pubmed/25248443
Li N, Yu J, Cao X, et al. A novel p. Gly630Ser mutation of COL2A1 in a Chinese family with presentations of Legg-Calve-Perthes disease or avascular necrosis of the femoral head. PLoS. 2014;9:e100505. http://www.ncbi.nlm.nih.gov/pubmed/24949742
Young ML, Little DG, Kim HKW. Evidence for using bisphosphonate to treat Legg-Calve-Perthes disease. Clin Orthop Relat Res. 2012;470:2462-2475. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830104/
Daniel AB, Shah H, Kamath A, Guddettu V, Joseph B. Environmental tobacco and wood smoke increase the risk of Legg-Calve-Perthes disease. Clin Orthop Relat Res. 2012;470:2369-2375. http://www.ncbi.nlm.nih.gov/pubmed/22090357
Loder RT, Skopelia EN. The epidemiology and demographics of Legg-Calve-Perthes disease. ISRN Orthop. 2011;2011:504393. http://www.ncbi.nlm.nih.gov/pubmed/24977062
Vosmaer A, Pereira RR, Koenderman JS, Rosendaal FR, Cannegieter SC. Coagulation abnormalities in Legg-Calve-Perthes disease. J Bone Joint Surg Am. 2010;92:121-128. http://www.ncbi.nlm.nih.gov/pubmed/20048104/
Miyamoto Y, Matsuda T, Kitoh H, et al. A recurrent mutation in type II collagen gene causes Legg-Calve-Perthes disease in a Japanese family. Hum Genet. 2007;121:625-629. http://www.ncbi.nlm.nih.gov/pubmed/17394019
Carney BT, Minter CL. Nonsurgical treatment to regain hip abduction motion in Perthes disease: a retrospective review. South Med J. 2004;97:485-488. http://www.ncbi.nlm.nih.gov/pubmed/15180025
Lappin K, Kealey D, Cosgrove A, Graham K. Does low birthweight predispose to Perthes’ disease? Perthes’ disease in twins. J Pediatr Orthop B. 2003;12:307-310. http://www.ncbi.nlm.nih.gov/pubmed/12973037
Neyt JG, Weinstein SL, Spratt KF, et al. Stulberg classification system for evaluation of Legg-Calvé-Perthes disease: intra-rater and inter-rater reliability. J Bone Joint Surg Am. 1999;81:1209-116. http://www.ncbi.nlm.nih.gov/pubmed/10505517
Kaniklides C, Sahlstedt B, Lonnerholm T, Moberg A. Conventional radiography and bone scintigraphy in the prognostic evaluation of Legg-Calvé-Perthes disease. Acta Radiol. 1996; 37:561-66. http://www.ncbi.nlm.nih.gov/pubmed/8688243
Kaniklides C. Diagnostic radiology in Legg-Calvé-Perthes disease. Acta Radiol Suppl. 1996;406:1-28. http://www.ncbi.nlm.nih.gov/pubmed/8792752
Reinker KA. Early diagnosis and treatment of hinge abduction in Legg-Perthes disease. J Pediatr Orthop. 1996;16:3-9. http://www.ncbi.nlm.nih.gov/pubmed/8747346
Lahdes-Vasama TT, Lamminen AE, Marttinen EJ, Merikanto JE. MRI imaging in late sequelae of Perthes’ disease: imaging findings and symptomatology in ten hips. Pediatr Radiol. 1996;26:640-45. http://www.ncbi.nlm.nih.gov/pubmed/8781103
Loder RT, Farley FA, Herring JA, Schork MA, Shyr Y. Bone age determination in children with Legg-Calvé-Perthes disease: a comparison of two methods. J Pediatr Orthop. 1995;15:90-94. http://www.ncbi.nlm.nih.gov/pubmed/7883936
Uno A, Hattori T, Noritake K, Suda H. Legg-Calvé-Perthes disease in the evolutionary period: comparison of magnetic resonance imaging with bone scintigraphy. J Pediatr Orthop. 1995;15:362-67. http://www.ncbi.nlm.nih.gov/pubmed/7790496
Kaniklides C, Lonnerholm T, Moberg A, Sahlstedt B. Legg-Calvé-Perthes disease. Comparison of conventional radiography, MR imaging, bone scintigraphy and arthrography. Acta Radiol. 1995;36:434-39. http://www.ncbi.nlm.nih.gov/pubmed/7619626
Suzuki S, Kasahara Y, Seto Y, et al. Arthroscopy in 19 children with Perthes’ disease. Pathological changes of the synovium and the joint surface. Acta Orthop Scand. 1994;65:581-84. http://www.ncbi.nlm.nih.gov/pubmed/7839839
Hochbergs P, Eckerwall G, Egund N, Jonsson K, Wingstrand H. Femoral head shape in Legg-Calvé-Perthes disease. Correlation between conventional radiography, arthrography and MR imaging. Acta Radiol. 1994;35:545-48. http://www.ncbi.nlm.nih.gov/pubmed/7946675
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:150600; Last Update:06/13/2007. Available at: http://omim.org/entry/150600 Accessed on: November 8, 2015.
Mayo Clinic for Medical Education and Research. Legg-Calve-Perthes Disease. May 30, 2014. Available at: http://www.mayoclinic.org/diseases-conditions/legg-calve-perthes-disease/basics/definition/CON-20035572 Accessed On: November 18, 2015.
Wiig O. Legg-Calve-Perthes Disease. Orphanet Encyclopedia, March 2009. Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2380 Accessed on: November 18, 2015.
Harris GD. Legg-Calve-Perthes Disease. Emedicine Journal, March 4, 2015. Available at: http://emedicine.medscape.com/article/1248267-overview Accessed on: November 18, 2015.
Varshney MK, Khan SA, Kumar A, Inna P. Osteochondroses. Emedicine Journal, November 2, 2015. Available at: http://emedicine.medscape.com/article/1254668-overview#a1 Accessed on: November 18, 2015.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100