Aneurysmal Bone Cyst Treatment & Management

Aneurysmal bone cysts (ABCs) generally are treated surgically, ^[34]  though injection therapy is also commonly performed. Currently available evidence has not established one type of therapy as clearly superior. ^[35]

Rarely, asymptomatic ABCs may be seen in which there is clinically insignificant destruction of bone. In such cases, close monitoring alone of the lesion may be indicated because of the evidence that some ABCs spontaneously resolve. When a patient is monitored in this manner, the diagnosis must be certain, and the lesion should not be increasing in size.

Some anatomic locations may be difficult to access surgically. If this situation is encountered, other methods of treatment, such as intralesional injection and selective arterial embolization, may be successful. In the future, advances in osteoinductive materials (eg, genetically engineered bone morphogenic protein [BMP]) may offer a less invasive treatment of ABC.

Systemic therapy with denosumab may be an option.

Impending pathologic fracture, especially a fracture of the hip, is a challenging problem and an indication for intervention, which often includes curettage, adjuvant treatment, and internal fixation.

Selective arterial embolization

Selective arterial embolization has shown much promise for ABCs in small studies. However, the number of cases treated with this therapy is not large, both because ABCs are rare and because selective arterial embolization has been available only since the 1980s. ^{[36, 37]}

With the use of angiography, an embolic agent is placed at a feeding artery to the ABC, cutting off the nutrient supply and altering the hemodynamics of the lesion. Various materials, such as springs and foam, have been used to create the emboli.

Selective arterial embolization has the advantage of being able to reach difficult locations, being able to save joint function when subchondral bone destruction is present, and making the complications that are associated with invasive surgery (eg, bleeding) less likely to occur. Selective arterial embolization may be performed within 48 hours before surgery to reduce the amount of intraoperative hemorrhage.

Some of the literature suggests that selective arterial embolization can be a primary treatment for ABC if the following conditions are met:

• Histologically confirmed tissue diagnosis of ABC
• Technical feasibility and safety
• Stability; no evidence of pathologic fracture or impeding fracture
• No neurologic involvement

Contraindications for selective arterial embolization include the following:

• Uncertain diagnosis; need to perform an open biopsy
• Structural instability; pathologic or impending fracture
• Neurologic symptoms
• Mechanical disruption
• Unsafe location to embolize with angiography or anatomically (eg, segmental arteries, certain cervical and thoracic areas that may lead to spinal cord ischemia, or subcutaneous bones [such as the clavicle or iliac crest] that may lead to adjacent skin necrosis and need for flap or skin graft coverage)

Intralesional injection

Intralesional injection may be attempted for cases in which surgical access is difficult and for those in which other modalities are contraindicated. ^[38] (Note: Do not use this approach if the patient has allergies to the injection components, a pathologic or impeding fracture, neurologic symptoms, or unbearable symptoms such as pain. Do not use intralesional injection if a more proven treatment is indicated.)

Contraindications for intralesional injection are as follows:

• Uncertain diagnosis; need to obtain an open biopsy
• Structural instability; pathologic or impending fracture
• Neurologic symptoms
• Mechanical disruption
• Allergy to injected substance
• Unbearable symptoms; lengthy time to resolution

Several studies have found percutaneous sclerotherapy with polidocanol to be effective in the treatment of ABCs. ^{[39, 40, 41]}

There has been case evidence for the use of calcitonin ^[42] and methylprednisolone injections in the regression of ABCs. This is thought to combine the inhibitory angiostatic and fibroblastic effects of methylprednisolone with the osteoclastic inhibitory effect and the trabecular bone-stimulating properties of calcitonin. The injections are performed under computed tomography (CT) guidance and anesthesia. Growth of the ABC must be closely monitored, and the treatment may need to be repeated several times. Years may pass before the ABC resolves.

ETHIBLOC (Ethicon, Norderstedt, Germany) injection is also performed under CT guidance and anesthesia. ^[43] The injected solution is a mixture of zein, oleum papaveris, and propylene glycol and acts as a fibrosing agent; an inflammatory reaction may occur after its administration. Bony healing may take months to years. Side effects (eg, localized thrombosis, pulmonary embolus, osseocutaneous fistula formation, and severe surrounding tissue necrosis) make it a poor first-line choice in the absence of an obvious surgical contraindication. ^[8]

Some case evidence has suggested healing improvement when systemic calcitonin treatment is used as an adjuvant to other treatment modalities.

An Australian study by Clayer in 15 patients with pathologically confirmed ABC suggested that percutaneous aspiration and injection of ABCs using an aqueous solution of calcium sulfate may have value. ^[11] All patients except one who reported pain before the procedure were completely without symptoms at 4 weeks post injection. The calcium sulfate was reabsorbed within 8 weeks. During the minimum 2-year follow-up period, two patients developed local recurrence of the lesion, one of whom later developed a pathologic fracture. Two other patients sustained pathologic fractures at 12 and 22 months post injection, respectively.

In several series, intralesional percutaneous injection of doxycycline was reported to be beneficial in inducing stromal cell necrosis, reversing bone destruction, and preserving neighboring anatomy including physes and subchondral bone. ^{[44, 45, 46, 47, 48]}  The principal proposed mechanisms of action for the success seen include the following ^[45] :

• Matrix metalloproteinase (MMP) and angiogenesis inhibition
• Osteoclast inhibition and apoptosis
• Enhanced osteoblastic bone healing

A small study by Meirlaen et al reported effective treatment of ABCs by means of percutaneous injection of demineralized bone matrix mixed with bone marrow. ^[49]

Systemic therapy

There is some evidence that denosumab, an inhibitor of receptor activator of nuclear kappa-B ligand (RANKL), may be useful as a treatment for ABCs; however, safety concerns have been expressed in relation to postdiscontinuance rebound, especially in the pediatric population. ^{[50, 51]}  In a narrative review focusing on the use of denosumab to treat various pediatric bone disorders, including ABCs, Wang et al found that this agent was efficacious in alleviating disease and that the adverse events occasionally reported could be minimized by early prevention, monitoring, and timely intervention. ^[52]

Radiotherapy

Radiotherapy was used in the past, but this treatment is generally contraindicated at present because of the risk of sarcoma induction, gonadal damage, and growth-plate disruption. Substantial risk is associated with treating a benign lesion with a therapy that can have damaging adverse effects, though radiation therapy is still occasionally used at low doses to treat surgically inaccessible lesions.

Extensive preoperative planning should be completed with the use of cross-sectional imaging. Embolization as a treatment or preoperative technique should be considered. When possible, a tourniquet should be used. Thought should also be given to what possible methods and materials may be needed to provide stability after ABC excision or resection.

Depending on the size and nature of the lesion, the patient's fluid volume and blood loss may have to be monitored closely.

Curettage and excision

The unusual stage 1 ABC can be treated with intralesional curettage ^[53] ; the more common stage 2 ABC is treated by intralesional excision. The difference between curettage and excision is that excision involves wide unroofing of the lesion through a cortical window by careful abrasion of all the surfaces with a high-speed burr and, possibly, local adjuvants such as phenol, methylmethacrylate (MMA), or liquid nitrogen. These adjuvants have been controversial because of a lack of firm evidence that they are effective; in addition, their use entails considerable risk.

En-bloc or wide excision is typically reserved for stage 3 ABCs that are not amenable to intralesional excision (eg, extensive bony destruction); the recurrence rate after en-bloc excision is about 7%. Reconstructive options after wide excision include structural allografting and reconstruction with either endoprostheses or allograft-prosthetic composites.

In the past, intralesional excision was the mainstay of treatment. The ABC is accessed, a window is opened in the bony wall, and then the contents of the ABC are removed. Excision of the walls with curettes, rongeurs, or high-speed burrs has been described. The intralesional method leaves more bony structure intact than en-bloc or regional resection.

Intralesional excision may also be used around joints and other vital areas to try to preserve function. The defect may then be filled with bone chips, bone strut, or other supporting material to add strength and to enhance healing of the excised area.

Concerns for local resection include the following:

• The region must be expendable and not affect function (eg, spinous process, rib, clavicle, or fibula)
• Some investigators believe that elective arterial embolization should be tried first if it is not contraindicated

Concerns for en-bloc excision of a deep lesion include the following:

• Resection destabilizes the area; some surgeons use more than one third of the bone width
• Loss of function (eg, joint loss) is possible
• Some investigators believe that elective arterial embolization should be tried first if it is not contraindicated

Concerns for intralesional removal include the following:

• The area may be surgically inaccessible
• Some investigators believe that elective arterial embolization should be tried first if it is not contraindicated

Adjuvant therapy

The surgeon may also use adjuvant therapy, which extends the area of treatment beyond that which can be physically excised. The use of liquid nitrogen, phenol, argon beam gas plasma photocoagulation, and polymethylmethacrylate (PMMA) may achieve an extended area of treatment.

The adjuvants involve the use of chemical, freezing, or thermal means to cause bone necrosis and microvascular damage to the walls of the physically excised cyst, disrupting the possible cause. Compared with en-bloc and regional resection, the use of adjuvants leaves more bone intact, and an increased area is treated compared with the area treated with intralesional resection alone.

Liquid nitrogen has been the most popular adjuvant and has often been described in the literature. After the ABC is exposed and a window is opened, liquid nitrogen may be applied by pouring it into the cyst through a funnel or by using a machine that is designed to spray the liquid onto the walls of the lesion. The surgeon should be sure to leave the window open, allowing the gas to escape.

A total of two or three cycles of freezing and thawing should be used to obtain maximum bone necrosis. The surrounding tissue, especially the neurovascular bundles, must be protected to ensure these structures are not damaged. Avoiding the use of a tourniquet with cryotherapy is suggested to keep the surrounding tissue vascularized, making it more resistant to freezing.

Phenol is much less often used as an adjuvant. Some authors have questioned the effectiveness of phenol because of its poor penetration of bony tissue compared with that of liquid nitrogen. However, phenol has had some success in certain studies, and it has the benefit of being easy to use. Phenol is simply applied to the mechanically removed walls by using soaked swabs. Any remaining phenol is removed with suction, and the cavity is filled with absolute alcohol. Finally, the cavity is irrigated with isotonic sodium chloride solution.

PMMA may also be used, though the effectiveness of its thermal properties in causing bone necrosis has been questioned in the literature. However, PMMA does have the benefit of rendering a large lesion mechanically sound and making it easier to recognize a local recurrence. If PMMA is used in a subchondral location, the joint surface should be protected by placing cancellous grafts or Gelfoam (Pharmacia & Upjohn Co, Kalamazoo, MI) before cementation. It is not clear that removing the cement and replacing it with a bone graft is necessary.

Argon beam coagulation has also been used in several studies, with some promising results. ^{[54, 55, 56]} One study noted that surgical treatment with curettage and adjuvant argon beam coagulation is an effective treatment option for ABC; the primary complication was postoperative fracture. ^[55]

An additional study found that argon beam photocoagulation, while avoiding the toxic effects of phenol, yielded statistically equivalent recurrence rates, functional outcomes, and complication rates in the treatment of benign-aggressive bone tumors. ^[56] However, the authors also noted an increased fracture rate in the argon beam photocoagulation cohort as compared with the phenol cohort.

Concerns for adjuvant intralesional therapy include the following:

• Substances such as liquid nitrogen and phenol could penetrate tissues and damage the surrounding structures, with neural and vascular tissues being at particularly high risk; for this reason, some investigators discourage the use of intralesional therapy in the spine
• Caution should be used in areas prone to fracture; liquid nitrogen and argon beam photocoagulation can make the surrounding bone stock more brittle and thus increase the likelihood of fracture

Additional considerations

It should be noted that special consideration is necessary in dealing with ABCs that are near open physes. The reader is referred to the literature for general considerations when operating around physes. The reported rate of physeal injury is significant, and patients and their families must be made aware of this possibility. Furthermore, it has been shown that attempts to spare the adjacent physes by performing a less-than-aggressive curettage of ABCs have resulted in increased risk of local recurrence in patients with open growth plates. ^{[57, 58]}

Spinal ABCs usually cause neurologic symptoms and pose treatment challenges. The details of surgical excision can be found elsewhere. There is evidence to support an attempt at one or two trials of selective arterial embolization before surgical excision.

A group in Japan developed an endoscopic approach to the treatment of ABC. ^[59] They successfully treated four patients with ABCs that lacked the aneurysmal component. The technique was completed with a variety of curettes, ball forceps, Kirschner wires (K-wires), an arthroscope, and a drill. The method may leave a more stable structure and is minimally invasive.

Treatment for a secondary ABC is that which is appropriate for the underlying lesion.

Activity modification should be as tolerated to the fitness of the patient, the anatomic location of the surgery, and the extent of the surgery and reconstruction. Mechanical or chemical prophylaxis against deep vein thrombosis may also be indicated.

Complications can vary with the location in which the ABC arises. Many of these are related to the proximity of the surrounding tissues.

Universal complications that have been described with surgery include the following:

• Recurrence
• Blood loss
• Wound infection
• Wound slough
• Wound hematoma
• Osteomyelitis
• Damage to the surrounding tissue
• Possible physis damage
• Pulmonary embolism (PE)

Additional complications that have been shown with spinal locations include the following:

• Tear of the dura
• Transient spastic paralysis from hematomas
• Tear in the vena cava
• Persistent back ache
• Deformity
• Neurologic symptoms

Complications that are associated with liquid nitrogen include the following:

• Rare gas embolism
• Rare late fracture
• Wound necrosis
• Damage to the surrounding tissue (eg, neurovascular bundles, physis)

A complication that is associated with phenol is necrosis of the surrounding tissue exposed to the phenol (eg, neurovascular bundles, physis).

A complication that is associated with selective arterial embolization is unintentional embolization of a vital area.

Finally, fracture risk may be elevated in those adjuvantly treated with argon beam photocoagulation, particularly in weightbearing bones.

When the diagnosis of ABC is suspected or confirmed, consultation with an orthopedic oncologist should be obtained.

Recurrence usually happens within the first year after surgery, and almost all episodes occur within 2 years. ^{[41, 60, 40]} However, patients should still be monitored on a regular basis for 5 years. It is beneficial to detect recurrence early when the lesion is still small and easier to treat. Children should be monitored until they have reached maturity to ensure that any possible recurrence does not cause deformity or interfere with their growth. Any patients who have received radiation should be monitored for life because of the risk of secondary sarcoma.