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.
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:
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For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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