A bone cyst is an abnormal, non-cancerous cavity that forms within the bone structure, typically filled with fluid or semi-solid material. These lesions often arise during skeletal growth, commonly affecting children and adolescents. While generally benign, a cyst can weaken the bone, sometimes leading to a pathologic fracture from an otherwise minor injury. Determining the precise cause requires specific classification, as the underlying mechanisms of formation differ widely between types.
Basic Classification of Bone Cysts
Bone cysts are categorized into two groups based on their origin. Primary cysts, such as Simple and Aneurysmal Bone Cysts, are lesions where the cystic formation is the main event and occurs without a clear preceding condition. These are sometimes referred to as idiopathic, meaning the exact cause is not always known.
Secondary bone cysts, in contrast, form as a complication or manifestation of a separate, pre-existing disease process. This category includes lesions that arise within other benign tumors or are a direct result of systemic metabolic disorders. The location of the cyst is often a clue to its classification, with many primary types favoring the metaphysis—the area of growth near the ends of long bones.
Causes of Simple and Aneurysmal Bone Cysts
Simple bone cysts (SBCs), also known as unicameral bone cysts, are characterized by a single fluid-filled cavity and primarily affect children and teenagers. The exact cause remains unknown, though several theories attempt to explain their formation. One hypothesis suggests a localized disturbance in bone circulation, specifically a failure of normal venous drainage within the cancellous bone.
This circulatory obstruction could lead to increased fluid pressure and accumulation, forming the characteristic serosanguineous (thin, watery, blood-tinged) cavity. Another theory posits that SBCs result from a localized defect or failure in the maturation of bone tissue near the growth plate. The cyst lining itself may secrete an enzyme that contributes to localized bone breakdown, sustaining the cystic process.
Aneurysmal bone cysts (ABCs) are expansile, blood-filled lesions that have a distinct and more complex etiology. While historically considered a purely reactive process, current evidence suggests that most primary ABCs are neoplastic, meaning they arise from a new, abnormal growth of tissue. This is supported by the finding of specific genetic alterations in approximately 70% of primary ABC cases.
These genetic changes involve a rearrangement of the USP6 gene, typically through a chromosomal translocation. The most common translocation is between chromosomes 16 and 17, placing the USP6 gene under the control of a highly active promoter gene, such as CDH11. This overexpression of USP6 leads to the proliferation of specific spindle cells within the cyst, which then dysregulate bone remodeling and inhibit the maturation of bone-forming cells.
The resulting abnormal tissue forms the characteristic cavernous, blood-filled spaces separated by fibrous septa. These genetic rearrangements are found exclusively in the spindle cells of primary ABCs, underscoring the distinction between the two types. Although ABCs are aggressive locally, the presence of the USP6 gene rearrangement firmly establishes the lesion as a benign tumor rather than a simple vascular anomaly.
Bone Cysts Arising from Pre-existing Conditions
A significant number of cystic bone lesions are not primary formations but are secondary to another underlying disease or tumor. In these instances, the “cause” of the cyst is the original condition that weakened or altered the bone structure. The term Brown Tumor, for example, describes a cyst-like lesion that is a skeletal manifestation of uncontrolled hyperparathyroidism.
Excessive secretion of parathyroid hormone (PTH) causes overactive bone resorption by stimulating osteoclasts, leading to localized bone loss. This rapid bone destruction results in bleeding and the subsequent ingrowth of fibrous tissue and macrophages, forming a mass. The brown coloration of the lesion comes from the large amounts of hemosiderin, an iron-storage complex, that these macrophages accumulate from broken-down blood.
Fibrous Dysplasia (FD) is another condition that can lead to secondary cystic changes. FD is a genetic disorder where normal bone is replaced by abnormal, fibrous, and poorly formed bone tissue. The disorganized nature of the fibrous tissue within the bone can sometimes undergo nonspecific cystic degeneration, forming fluid-filled cavities.
Furthermore, some primary bone tumors can develop secondary aneurysmal bone cyst (ABC) components. Giant Cell Tumors (GCTs) are the most common primary lesion to have this complication, with secondary ABC formation reported in about 14% of GCT cases. This secondary formation is thought to be a reactive process, possibly due to hemorrhage, necrosis, or localized changes in blood flow within the original tumor.