About vanishing bone disease
What is vanishing bone disease?
Gorham's disease (GD) is an extremely rare bone disorder; fewer than 200 cases are reported in the medical literature. It is characterized by bone loss (osteolysis) often associated with swelling or abnormal blood vessel growth (angiomatous proliferation). Bone loss can occur in just one bone or spread to soft tissue and adjacent bones.
Although the disease may strike any of the bones of the body, it is more often recognized earlier when the bones at the top of the head (calvarium) and/or the mandibles are involved.
Because of its rarity, the disorder often goes unrecognized. As a result of that, coupled with a lack of agreement on how best to treat Gorham's disease once it is recognized, treatment may often be delayed. The cause of Gorham's disease is unknown.
What are the symptoms for vanishing bone disease?
The symptoms of GSD depend upon the specific bones involved. The ribs, spine, pelvis, skull, collarbone (clavicle), and jaw are the most commonly affect bones in GSD. In some cases, affected individuals may rapidly develop Pain and Swelling in the affected area. In other cases, affected individuals may experience a dull Pain or ache or generalized Weakness that builds over time. Trauma is often a trigger of the initial presentation of the disease. Bones affected by GSD are prone to pathological fractures.
When GSD affects the maxillofacial area, pain, loose teeth, fractures and facial deformity may develop.
Involvement of the spine or skull base can be associated with neurological complications. Involvement of the spine can also potentially result in chronic or acute Pain or Paralysis (paraplegia). Some medical references have reported an association with meningitis in such cases. Meningitis is Inflammation of the membranes (meninges) covering the brain and spinal cord, usually due to infection.
Involvement of the thoracic cage can lead to chylothorax, which is the accumulation of chyle in the space between the membranes (pleura) that line the lungs and chest cavity. Chyle is a milky fluid that consists of lymph and fat. Chylothorax can cause difficulty breathing (dyspnea), rapid breathing (tachypnea), chest Pain or respiratory compromise. Chylothorax can eventually progress to cause life-threatening respiratory complications. Chylous ascites (accumulation of chyle in the abdominal cavity) can also occur in patients with GSD.
Some individuals with GSD may develop abnormal fluid accumulation around the heart (pericardial effusion). Specifically, the fluid accumulates in the pericardium, the sac-like structure that surrounds the heart.
Clinical Course – Outcomes The prognosis for GSD patients is uncertain and variable and depends on the extent of the disease, the part of the body involved, and underlying proliferative progressiveness of the disease. Pulmonary involvement with chylothorax or spinal involvement may confer a poor prognosis, sometimes leading to death. In other cases, lesions may remain stable for long periods of time.
What are the causes for vanishing bone disease?
The exact cause of GSD is unknown. No environmental, immunological or genetic risk factors have been identified. Most cases occur randomly for no known reason (sporadically).
Bone loss in GSD is accompanied by the uncontrolled growth (proliferation) of lymphatic tissue. The signal that stimulates this abnormal proliferation of vascular and lymphatic tissue is unknown. However, laboratory research has implicated specific growth factors (e.g. vascular endothelial growth factor [VEGF]) in modulating lymphatic vessel growth and bone development and destruction. Future investigations will reveal the role these growth factors serve in promoting GSD.
Some investigators have speculated that circulation issues lead to a deficiency of oxygen being delivered to affected areas, which, in turn, causes changes in pH and promotes the activity of specific enzymes that ultimately cause the destruction of bone.
Osteoclasts are large cells that degrade bone. Several reports suggest that osteoclasts play a role in the resorption of bone in GSD. Active osteoclasts have been observed in histological samples from some patients with GSD. Additionally, CTX-1 (a circulating marker of osteoclast activity) has been reported to be elevated in several GSD patients. It has been suggested that osteoclast precursors in GSD patients are more sensitive to osteoclast-inducing factors than osteoclasts precursors in unaffected individuals. Also, interleukin-6 (a factor that induces osteoclast formation) has been reported to be elevated in some patients with GSD. More recently, a basic science study revealed that lymphatic endothelial cells (LECs) express a high level of macrophage colony stimulating factor (M-CSF), a factor that induces the development of osteoclasts. Interestingly, LECs were found to induce osteoclast formation and activity in an M-CSF dependent manner. More work is required to elucidate the role of osteoclasts in GSD.
Taken together, the specific reason that GSD develops is simply not well understood. More research is necessary to determine the exact cause and underlying mechanisms that ultimately result in GSD.
What are the treatments for vanishing bone disease?
GSD (and GLA) can present at any age. Diagnosis, treatment, and care generally require a multidisciplinary team. Access to care is available through the worldwide Vascular Anomalies Clinical Network. For more information on expertise and consult, contact the Lymphangiomatosis & Gorham’s Disease Alliance.
There is no consensus in the medical literature as to what is the most effective treatment for GSD. Treatment is usually directed toward the specific symptoms that are apparent in each individual.
Surgery to remove the affect areas of bone has been performed to treat individuals with GSD. In some cases, a bone graft, which stimulates or augments the formation of new bone, may be used in conjunction with the surgical removal of affected bone. However, bone grafts can only be used after stabilization of the osteolytic process. Consequently, some physicians prefer the use of artificial (prosthetic) bone to replace bone removed by surgery.
Radiation therapy, sometimes in conjunction with surgery, has also been used to treat individuals with GSD. Radiation therapy has proven effective in treating some affected individuals, achieving pain relief and arresting the spread of osteolysis. Radiation therapy has also been effective in treating chylothorax, which is sometimes associated with GSD.
According to cases reported in the medical literature, positive results have been achieved with a total dose of 30 to 45 Gy. In one reported case, positive results were achieved using a total dose of 15 Gy in an individual with GSD affecting the upper extremity.
What are the risk factors for vanishing bone disease?
GSD usually affects children and young adults under the age of 40. However, the disorder has been reported in an infant less than one month old and an adult more than 70, suggesting GSD can potentially affect individuals of any age. Some medical sources state that males are affected more often than females. Other medical sources state that the ratio is even (1:1). More than 300 affected individuals have been reported in the medical literature. Because GSD is so rare, many cases go undiagnosed or misdiagnosed making it difficult to determine the disorder’s true frequency in the general population.