Osteochondromas are caused by abnormal behavior at the growth plates, the strips of cartilage near the ends of bones where new bone forms during childhood and adolescence. About 85% of cases are solitary (a single tumor) and arise without a clear inherited cause, while the remaining 15% occur as part of a genetic condition called hereditary multiple osteochondromas. In both forms, the underlying problem is the same: cartilage cells that should stay organized within the growth plate instead escape outward and form a bony lump capped with cartilage.
How Growth Plate Cells Go Wrong
During normal bone growth, cartilage cells at the growth plate multiply in orderly columns, gradually harden into bone, and extend the skeleton lengthwise. An osteochondroma forms when fragments of that growth plate cartilage break through the outer shell of the bone and begin growing on the surface instead. This escape route opens through a defect in a structure called the ring of Ranvier, a band of tissue that normally acts as a fence around the edge of the growth plate, keeping cartilage cells contained.
Once outside that boundary, the displaced cartilage cells continue to grow and ossify just as they would inside the bone, producing a stalk or broad base of normal-looking bone topped by a cap of cartilage. The cartilage cap is the active growing portion of the tumor. Because growth depends on the same process that drives normal skeletal development, osteochondromas typically slow or stop growing once a person reaches skeletal maturity and the growth plates close.
The Role of EXT1 and EXT2 Genes
The clearest genetic link involves two genes, EXT1 and EXT2, which provide instructions for building an enzyme that assembles a sugar-based molecule called heparan sulfate. This molecule sits on the surface of cartilage cells and in the surrounding tissue, where it helps relay signals from growth factors that tell cells when to divide, mature, and stop growing.
When EXT1 or EXT2 is mutated, heparan sulfate is either drastically reduced or absent from the cartilage matrix. Immunohistochemical studies have shown that in affected cartilage, heparan sulfate no longer reaches the cell surface at all. Instead, it gets trapped inside the cell, accumulating in an internal compartment called the Golgi apparatus. Without heparan sulfate in the right place, multiple signaling pathways go haywire simultaneously. Two of the most important, the pathways that coordinate how quickly cartilage cells mature and when they stop dividing, lose their normal checks and balances. The result is premature and disorganized bone formation that pushes outward as a tumor.
Hereditary Multiple Osteochondromas
When a person inherits a mutated copy of EXT1 or EXT2 from a parent, they develop multiple osteochondromas rather than a single one. This condition follows an autosomal dominant inheritance pattern, meaning only one copy of the faulty gene is needed. Penetrance is essentially complete in males (100%) and nearly so in females (96%), so almost everyone who carries the mutation will develop at least some tumors. The rare instances of someone carrying the gene without visible tumors have occurred almost exclusively in women.
Because each child of an affected parent has a 50% chance of inheriting the mutation, multiple family members across generations are typically affected. The hereditary form tends to produce tumors at many skeletal sites and can cause complications like limb-length differences and bowing of the forearms that solitary osteochondromas rarely produce.
Radiation Exposure in Childhood
Osteochondromas can also develop as a side effect of radiation therapy received during childhood. Both localized radiation (targeting a specific area) and total body irradiation have been linked to tumor formation, particularly when children are treated at a young age while their growth plates are still highly active. In the general population, osteochondromas are estimated to occur in 1% to 3% of people, but in children who underwent bone marrow transplants with total body irradiation, the reported incidence jumps to 6% to 24%.
One proposed explanation is that radiation keeps the growth plates open longer than they would otherwise remain, giving displaced cartilage cells a wider window to form tumors. Another is that radiation directly damages the EXT genes in growth plate cells, mimicking the genetic defect seen in the hereditary form. Supporting this idea, children who develop osteochondromas after total body irradiation often have multiple tumors distributed across the skeleton in a pattern that closely resembles hereditary multiple osteochondromas rather than the typical solitary lesion.
Why They Appear During Adolescence
The connection between osteochondromas and active bone growth explains why these tumors overwhelmingly appear in young people. In a review of 431 patients at a single institution in southern China, about 65% were first diagnosed between birth and age 20. The peak age range was 11 to 20 years, accounting for nearly 43% of all cases. The overall average age at diagnosis was about 21 years, though the full range extended from infancy to age 71.
The most common location was around the knee, which makes sense because the growth plates at the lower end of the thighbone and the upper end of the shinbone are among the most active in the body during the adolescent growth spurt. Most tumors were discovered during periods of rapid skeletal growth, when the growth plate is producing cartilage at its highest rate and the opportunity for cells to escape through defects is greatest.
Risk of Malignant Transformation
Solitary osteochondromas carry an extremely low risk of becoming cancerous. The more meaningful concern applies to hereditary multiple osteochondromas, where malignant transformation is estimated to occur in 1% to 5% of cases. When transformation does happen, it produces a secondary chondrosarcoma (a cartilage-based cancer) about 94% of the time. This progression involves additional genetic changes on top of the original EXT mutation.
The warning sign is a tumor that begins growing again after skeletal maturity, or a cartilage cap that measures thicker than expected on imaging. Because the cartilage cap normally shrinks and thins once the growth plates close, any renewed growth in adulthood is treated as suspicious and typically warrants closer monitoring or removal.