Diagnosis and Management of Legg-Calvé-Perthes Disease in the Obese Pediatric Population

Abstract

Legg-Calvé-Perthes Disease (LCPD) is a condition marked by temporary blood flow disruption to the proximal femur, commonly afflicting children aged 15 and younger. The etiology of the disease is often idiopathic and involves the development of avascular necrosis of the femoral head, subsequently leading to bone weakening and deformity. Obesity exacerbates LCPD, correlating with delayed diagnosis, increased disease severity, and bilateral involvement. Leptin, growth hormone, and other inflammatory mediator alterations in obese individuals contribute to the pathogenesis. Treatment ranges from conservative measures to surgery, with particular challenges in obese patients. An improved understanding of the impact of obesity on LCPD progression is crucial for tailored management and optimal outcomes.

Introduction

Legg-Calvé-Perthes Disease (LCPD) is a temporary disruption of blood flow to the capital femoral epiphysis in preadolescent children¹. The femoral neck and head receive nutrients and oxygen from the epiphyseal branch of the median circumflex artery, which originates from the femoral artery¹. Disruption of the blood supply from the medial circumflex or epiphyseal branches causes avascular necrosis of the subchondral cortical bone in the capital femoral epiphysis (Figure 1)¹. The affected bone then becomes weak, fractures easily, and begins to die. The body resorbs the infarcted bone, which leads to the re-establishment of the femoral epiphysis when osteoblastic activity takes control¹. The new femoral head may be enlarged or flattened¹.

Figure 1:

Vascular supply to the femoral head (a). Medial circumflex artery blockage (b) or lateral epiphyseal vessel blockage (c) causing avascular necrosis. Adapted from Joseph et al.¹

Potential etiologies of LCPD include trauma, steroid use, and coagulopathy; however, the disease largely remains idiopathic². Children typically present with a limping gait and restricted hip mobility, often experiencing internal rotation and abduction limitations. Depending on the stage of the disease, differences in leg length may occur due to a collapsed epiphysis³. Some children can present with isolated knee pain, delaying the diagnosis due to the absence of pain in the groin or thigh³. Hip pathology presenting as knee pain is well-documented in the pediatric literature^{4, 5}. Therefore, in cases where examination of the knee is normal, the child should be evaluated for hip pain upon rotation and abduction⁶. Typically, internal rotation is more affected than external rotation⁶.

Plain film X-ray imaging using the anteroposterior pelvis and frog-leg lateral views is recommended if LCPD is suspected⁷. Early findings of LCPD include joint space widening due to hypertrophy of the epiphyseal cartilage, a smaller and denser epiphysis, and a subchondral fracture of the anterolateral epiphysis in the setting of osteonecrosis (Crescent sign)⁷. Femoral head flattening, decreased perfusion on bone scans, and marrow changes indicated on an MRI may be observed as the disease progresses⁷.

Classification

Legg-Calve Perthes disease is divided into four stages based on the Waldenstrom criteria: initial/necrosis (stage I), fragmentation (stage II), reossification (stage III) and healed/residual (stage IV)^{7, 8}. The Waldenstrom criteria are based on radiographic changes that occur as the disease progresses (Figure 2)^{7, 8}. In stage I, the osteonecrosis process begins. Radiographs may show a dense and flattened femoral head, and the medial joint space widens⁷. This phase generally lasts from several months to a year and is characterized clinically by mild pain and potentially an altered gait or limp. The Crescent sign marks the beginning of stage II which involves the reabsorption of necrotic bone⁷. The femoral head has a fragmented appearance noticeable on radiograph. Hip symptoms are most pronounced in this stage, which may present for a year or longer⁷. In stage III, continued resorption of necrotic bone occurs with new bone formation, and early remodeling of the femoral head⁷. This is the longest phase of the disease which can last 2–3 years. In stage IV, the bone becomes homogenous, but the femoral head can become enlarged, flattened, and have a short, wide neck⁷. The final shape of the head and its congruence in the acetabulum will greatly determine long term outcomes. Remodeling will continue until full skeletal maturity⁷.

Figure 2:

Waldenstrom classification of LCPD. Stage I is the initial stage followed by Stage II, also known as fragmentation. In Stage I, the blood supply to the femoral head is disrupted, leading to patchy areas of osteonecrosis. The head becomes sclerotic and flattened, and the medial joint space widens. Stage II begins with the presence of a subchondral lucent line (Cresent sign). Osteoclastic activity resorbs the dead bone and osteoblasts produce new, immature bone, giving a patchy, or fragmented appearance to the femoral head. Stage III and Stage IV are reossification and residual stages, respectively. In stage III, there is progressive maturation of bone, continued resorption of necrotic bone, and early remodeling of the femoral head which continues into Stage IV. The bone becomes homogenous, but the head can become enlarged (coxa magna), flattened (coxa plana) and have a short, wide neck (coxa breva). Remodeling will continue until full skeletal maturity. Images obtained from The Shriners Hospital, Greenville, SC.

Treatment and Management

Treatment modalities for LCPD range from self-management of the disease to surgical interventions. Conservative treatment options for LCPD utilize anti-inflammatory medications, rest, decreased physical activity, and physical therapy⁹. Additionally, bracing the hip joint can benefit patients with a deformed femoral head before re-ossification. A wide abduction brace (A-frame brace) can hold the joint inside the acetabulum until the bones have ossified⁹. However, while conservative, this option is not universally recommended due to the physical restrictions of the brace. Before considering surgical options for LCPD, it is essential to regain the hip range of motion with physical therapy⁹.

Surgical interventions for LCPD include femoral osteotomy, salter osteotomy, and arthrodiastasis⁹. Femoral osteotomy realigns the hip joint, restores joint congruency, and reduces femoroacetabular impingement. Salter pelvic osteotomy is typically indicated in younger patients without femoral head deformity or subluxation, allowing for femoral head remodeling during growth. Arthrodiastasis is a joint distraction procedure to reduce pain and increase the range of motion in the hip⁹. Age and lateral pillar classification are two factors that should be considered to determine whether conservative or surgical treatment would result in the best patient outcome⁹.

Presentation Variations in Obese LCPD Patients

Since 2010, there has been a steady increase in the number of overweight and obese children in the United States, with an incidence reaching 19.7% in the year 2020^{10, 11}. The chronic inflammatory state associated with obesity causes metabolic and vascular alterations that can affect blood flow to the hip joint, contributing to the development of LCPD¹². In fact, one study showed LCPD is twice as common in the obese population compared to healthy weight children¹³. With obesity being an identified risk factor for LCPD and current rates of pediatric obesity on the rise, it is important to understand the effects obesity has on the developing individual with LCPD. Children affected by LCPD are still in a prime orthopedic developmental stage, as nearly half of bone mineral accrual occurs within two years of the individual’s adolescent growth spurt¹⁴. Increasing amounts of body fat can negatively impact the ability of the body to develop peak bone mass¹⁴. Obesity causes the common mesenchymal stem cells to develop into fat cells rather than osteoblasts. The proliferation of fat cells occurs due to the reduced expression of genetic factors needed to shift differentiation towards osteoblasts¹⁵. This results in bone marrow filled with fat rather than trabecular bone, leading to a weaker bone¹⁵.

Additionally, with increased body mass in the form of adipose tissue comes an increase in inflammatory factors that can play a role in bone development. Studies show that macrophages are abundant in adipose tissue, producing high levels of Interleukin-6 (IL-6) and C-reactive protein (CRP). Elevated levels of pro-inflammatory cytokines create a chronic state of low-grade inflammation in obese individuals¹⁵. These same pro-inflammatory cytokines support osteoclast formation, leading to generalized bone loss¹⁵.

In addition to negative changes in bone development, obesity greatly amplifies the classic presentation and prevalence of LCPD¹³. As hip contact pressure is based on the weight of the child, obese children with LCPD are more likely to present with bilateral necrosis rather than classic unilateral deformity due to increased hip pressure¹³. Additionally, compared to their healthy weight counterparts, obese and overweight children are diagnosed at Waldenstrom stage 3, whereas healthy weight children are most commonly diagnosed at stage 1 or 2¹³. This may be due to a delay in obese LCPD patients seeking medical intervention as there is a strong association between obesity and healthcare avoidance¹⁶. Alternatively, LCPD may progress more rapidly in obese children as they are at an increased risk of lower extremity injuries and experience delayed bone healing^{13, 17}.

Factors that Impact LCPD Pathogenesis

Obesity has been shown to affect the progression and presentation of LCPD; however, the mechanisms by which obesity influences disease development are not well understood. Three factors impacted by obesity and likely contributing to LCPD pathogenesis are leptin levels, inflammation, and growth hormone production.

Leptin

Leptin is a hormone released from adipose tissue responsible for regulating the balance between food intake and energy expenditure¹⁸. The amount of leptin produced is directly proportional to the amount of adipose tissue present. Therefore, high leptin levels are associated with obesity, impacting the integrity and architecture of the bones. Increased leptin can inhibit bone formation, causing ischemic necrosis and degeneration of the femoral head^{19, 20}. Additionally, high leptin levels correlate with upregulation of vascular endothelial growth factor (VEGF), which should stimulate blood vessel formation to revascularize the necrotic bone²⁰. However, over time, the leptin receptor becomes desensitized, inhibiting bone revascularization¹⁹.

Although LCPD is more prevalent in males, females often exhibit a more severe form of the disease²¹. This disparity in prevalence and presentation of LCPD between the two sexes may be due to anatomical or hormonal differences²¹. For example, the intra-articular ring of the proximal femur is often more discontinuous in males than females, which may account for their increased susceptibility to LCPD²¹. Additionally, females between 5–15 years of age naturally have elevated leptin levels²². Leptin is believed to play a role in LCPD pathogenesis as the amount of circulating leptin correlates with disease severity and treatment outcome in LCPD patients¹⁹. Therefore, the late presentation of LCPD in females and the associated poor outcomes may be due to increased leptin production²¹.

Inflammation

Obesity and overeating are linked with increased oxidative stress and elevated levels of inflammatory markers²³. These signals, such as TNF-α, IL-6, and CRP, play a role in bone remodeling and are associated with bone mineral density and osteonecrosis pathophysiology²⁴. IL-6 also directly upregulates osteoclasts and downregulates osteoblasts, likely contributing to the ischemic osteonecrosis seen in LCPD patients²⁵. In support of this, higher levels of IL-6 were detected in the synovium, synovial fluid, and articular cartilage of piglets with surgically induced ischemic osteonecrosis of the right femoral head²⁵. Elevated levels of CRP are found in obese individuals as well as individuals with lower bone mineral density at the femoral neck, placing them at a higher risk for fractures. The increased levels of CRP in obese patients could augment the increased fracture risk seen in LCPD patients²⁴.

Growth Hormone

Another possible etiology of LCPD is glucocorticoid use because it suppresses growth hormone (GH) production²⁶. GH induces the generation of IGF-1, or somatomedin 1, in the liver and regulates the paracrine production of IGF-1 in many other tissues. IGF-1 is a major mediator of pre- and postnatal growth. In obese children, GH secretion is profoundly suppressed²⁷. The decrease in GH during childhood due to obesity leads to the depletion of bone mineral density, as IGF-1 is essential for longitudinal growth, skeletal maturation, and bone mass. Animal studies have shown that low IGF-1 stimulates osteonecrosis, which is the clinical hallmark of LCPD²⁸.

Pediatric patients with acute presentation of LCPD have significantly lower levels of IGF-1 compared to healthy age- and sex-matched controls²⁹. These low levels of IGF-1 are associated with persistently low rates of soft tissue collagen synthesis and enhanced rates of collagen breakdown. Obesity also causes a low IGF-1 state resulting in a lack of skeletal maturity and bone density, likely explaining why obese LCPD children are diagnosed at a later Waldenstrom stage. Due to the link between IGF-1 and LCPD, growth hormone has been researched as a possible treatment option³⁰.

Treatment Considerations for Obese LCPD Patients

While not an outright contraindication for surgery, obesity presents a challenge to the orthopaedic surgeon. Obese pediatric patients are at a higher risk of experiencing longer operative times and developing surgical site infections and wound dehiscence compared to their healthy weight counterparts³¹. In obese patients undergoing hip surgery, anesthesia time and incision size are typically increased, with the latter directly correlating with the patient’s BMI, where the incision length is one-third the BMI. The elongated incision size also corresponds to an increased wound healing time³². Furthermore, obese children face an elevated risk of developing deep vein thrombosis due to chronic inflammation, platelet activation, and disorders of the reticuloendothelial system associated with obesity³². Because of the increased risk of adverse outcomes, conservative methods have become the primary treatment option in this patient population. While lower, risks associated with non-operative management still exist. For instance, the body habitus of obese patients can create difficulties with maintaining optimal healing angles with casting, leading to malalignment and further growth plate disturbances³². There are also concerns about limited activity potentially exacerbating obesity; however, recent research has shown that weight-bearing restrictions did not lead to increased BMI in children with LCPD³³. Additional research is needed to identify the best treatment options for obese children who are affected by LCPD.

Conclusion

LCPD is a self-limiting condition without a definitive cure, making it an important disease to recognize and diagnose early so appropriate management measures can be taken. This is especially true for children affected by obesity, as this is an established risk factor for LCPD. This disease affects children during prime developmental stages and can alter bone structure, leaving the child’s bones more fragile and susceptible to fractures. Similarly, patients with both LCPD and obesity experience a greater endocrine influence, as well as an increased risk for bilateral necrosis. The increased endocrine influence and higher likelihood of developing bilateral necrosis further exacerbate the severity of the disease. LCPD has a tendency to be diagnosed at a later stage in obese individuals, leaving the patient with permanent gait abnormalities and limited treatment options.

Providers should be aware of the atypical clinical presentation of LCPD in an obese child. Delayed diagnosis is directly correlated to increased morbidity and disability later in life. Prompt referral to an orthopedic surgeon, implementation of physical therapy, initiation of pain management, and coordination of care between orthopedic specialists and physical therapists are shown to increase patient outcomes³⁴. Understanding the impact obesity can have on LCPD presentation and progression will aid in early diagnosis to decrease long-term complications.