Legg-Calvé-Perthes disease happens when blood supply to the ball-shaped top of the thighbone (the femoral head) is disrupted in a growing child, causing the bone to weaken, break down, and eventually rebuild. The exact reason this blood supply gets cut off remains unknown in most cases, but researchers have identified several factors that raise a child’s risk. The condition affects roughly 12 per 100,000 children, with about 82% of cases occurring in boys, and it typically appears between ages 2 and 12.
Interrupted Blood Supply to the Hip
The femoral head in children depends on a few small arteries for its blood supply, primarily the lateral epiphyseal artery and the ligamentum teres artery. Unlike most bones in the body, which have multiple overlapping blood routes, the top of a child’s thighbone has limited backup circulation. If one of these arteries is blocked or compressed, the bone tissue loses oxygen and nutrients and begins to die, a process called avascular necrosis.
Animal studies have confirmed this mechanism directly. When researchers interrupted blood flow to the femoral head in piglets and rats, the bone developed damage that looked nearly identical to what doctors see on imaging in children with Perthes disease. The bone goes through predictable stages: it first weakens and collapses, then fragments as the dead tissue breaks apart, then slowly rebuilds with new bone over months to years. What triggers that initial loss of blood flow in a specific child, though, is where the picture gets complicated.
Blood Clotting Abnormalities
One of the more concrete theories involves inherited problems with blood clotting. Some children with Perthes disease have deficiencies in proteins that prevent excessive clotting, specifically protein C and protein S. These proteins normally keep your blood from forming clots where they shouldn’t. When levels are low, tiny clots can form in the veins draining the femoral head, raising pressure inside the bone and choking off blood flow.
In one study of eight Perthes patients, three had protein C deficiency and one had protein S deficiency. A fifth patient had trouble breaking down clots once they formed. That means five of eight children in the study had a measurable clotting problem that could explain how blood flow to the hip bone was disrupted. These clotting disorders often run in families without ever being diagnosed, sometimes only coming to light when a child develops Perthes or a relative has an unrelated clotting event later in life.
Secondhand Smoke Exposure
Exposure to cigarette smoke is one of the strongest environmental risk factors identified so far. A case-control study comparing 90 children with Perthes disease to 183 healthy children found that nearly 79% of the Perthes group were passive smokers, compared to 43% of controls. After adjusting for age and sex, children exposed to secondhand smoke were more than five times as likely to develop the disease.
Cigarette smoke damages blood vessels and promotes clotting, which fits neatly with the blood supply theory. Notably, while smoke exposure was strongly linked to whether a child developed Perthes in the first place, it did not seem to affect how severe the disease became or how well the hip healed afterward. The risk factor appears to act as a trigger rather than influencing the course of the disease once it starts.
Genetic Factors
Perthes disease sometimes clusters in families, and when it does, it typically follows an autosomal dominant inheritance pattern, meaning a child only needs to inherit the relevant gene variant from one parent to be at risk. Early research pointed to mutations in the COL2A1 gene, which helps build the collagen found in cartilage and connective tissue. However, most researchers today no longer believe COL2A1 mutations are a direct cause. The genetic contributors likely involve multiple genes that affect blood vessel development, clotting, or bone growth, but none have been definitively identified.
Low Birth Weight
Birth weight may also play a role. A review of 320 Perthes patients in Northern Ireland identified five sets of twins in the group, and in every case, the twin with the lower birth weight was the one who developed the disease. This suggests that conditions during pregnancy, such as restricted blood flow or nutrient delivery to the developing fetus, may set the stage for vulnerability in the hip’s blood supply years before symptoms appear.
ADHD and Mechanical Stress
Children with Perthes disease are about 1.5 times more likely to be diagnosed with ADHD than children without the condition, and the link is even stronger in girls (about twice the risk). This connection likely works in both directions. Hyperactive children put more mechanical stress on their hips through constant movement, jumping, and higher rates of injury, which could contribute to disrupting an already vulnerable blood supply. At the same time, Perthes and ADHD share overlapping risk factors, including socioeconomic deprivation and maternal smoking during pregnancy, so the two conditions may partly stem from common exposures rather than one directly causing the other.
How the Disease Progresses
Once blood supply is lost, Perthes disease moves through four stages. The initial stage, when the bone first begins to die, lasts roughly 4 to 6 months. During fragmentation, the weakened bone breaks into pieces as the body starts clearing dead tissue; this phase averages about 6 to 12 months. Reossification, when new bone gradually replaces the damaged tissue, is the longest stage, averaging around 51 months but sometimes lasting up to 10 years in some cases. The final residual stage is the permanent shape the femoral head takes once healing is complete.
That final shape determines a child’s long-term outlook. Doctors classify the healed hip on a five-point scale. A hip that returns to a normal round shape carries essentially no increased arthritis risk. A hip that heals with mild flattening or enlargement carries about a 16% lifetime risk of arthritis. More significant flattening pushes that risk to 58% to 78%, depending on how well the hip socket conforms to the reshaped bone. Children diagnosed before age 6 generally have better outcomes because they have more years of growth remaining for the bone to remodel.
Why No Single Cause Explains Every Case
The honest answer to “what causes Perthes disease” is that most cases have no single identifiable cause. Instead, the condition likely results from a combination of factors: a child may have a genetic tendency toward sluggish blood flow or easy clotting, be exposed to environmental triggers like secondhand smoke, and experience the kind of repetitive hip stress that comes with normal childhood activity or hyperactive behavior. Each factor narrows the margin of safety for an already precarious blood supply to the femoral head. When enough of these factors converge, the blood flow tips below what the bone needs to survive, and the disease process begins.