WHAT IS HETEROTOPIC OSSIFICATIONAND WHAT CAUSES IT?

Heterotopic ossification (HO) is the development of bone in areas in which it is not normally found. This usually creates the most problems around joints, where the presence of the excess ossification can lead to blocks to motion, irritation of the soft tissues, and even bony ankylosis of the affected joints. Soft-tissue ossification in areas remote from joints will often be asymptomatic but can cause local muscle and fascial irritation, and with this, symptoms of pain and dysfunction.

The formation of HO is associated with many differing conditions. A direct cause-and-effect relation has not been established; however, the most common associations are with burns, spinal cord injury, and trauma. It is also a problem that can develop with elective joint replacement arthroplasty, specifically total hip and knee arthroplasty. Head injury in association with traumatic fractures or dislocations will significantly increase the chances of acquiring this problem. HO that develops in patients with head injuries usually affects only areas of musculoskeletal injury, although the trauma may be fairly minor. In burn victims and patients with spinal cord injury, HO may develop around joints that have not had any specific injury to them, often being quite extensive and frequently causing ankylosis by bridging across normal joints.

It is postulated that a circulatory factor, released from the brain, is the common factor in burn and trauma victims that leads to the growth of the HO. Much work is yet to be done to fully isolate this factor. The factors seem to be subtypes of bone morphogenetic protein (BMP), with BMP-1, −4, and −6 found in pathologic specimens.¹ A correlation exists between the severity of the head injury and the risk for development of ectopic bone. The occurrence of autonomic dysregulation may predict the chance of development of HO in patients with severe head injury.² The role of prostaglandin E₂ has recently been suggested as a mediator in the differentiation of the progenitor cells.³

CLINICAL PROBLEMS ASSOCIATED WITH HETEROTOPIC OSSIFICATION

The causative factor of pain associated with HO is unclear. Pain associated with neurologic or vascular entrapment, or functionally restricting joint stiffness associated with HO, may be indications to consider HO resection.

As with many areas within orthopedic surgery, a full consideration of all of the clinical aspects of the problem is required before considering surgical intervention: Do the patient’s symptoms fit with the radiographic findings? Is the HO in a location where it can be safely removed without undue risk for harm to the associated soft tissues, including critical neurologic and vascular structures? Is the bone sufficiently mature to allow resection and not simply immediately re-form after it is removed? These are but some of the questions that must be answered before embarking on this type of technically demanding surgery. The purpose of this chapter is to guide clinicians regarding the optimal timing of surgical resection based on the best available evidence.

OPTIONS

Preoperative radiographic assessment of the HO is critical in terms of the decision to operate and acts as a guide through the surgical session. The use of plain radiographs, oblique views, and tomograms are helpful, but a computed tomographic (CT) scan is important to fully assess the extent and pattern of the bone formation. A three-dimensional reconstruction is a major help to conceptualize the HO. On the CT scan, a halo of inflammatory tissue around the bone mass may indicate continued activity of bone formation. Magnetic resonance imaging scanning may play a role in defining the location of adjacent critical neurovascular structures adjacent to a mass of HO.

The timing of surgical HO resection is of critical importance. There is a balance to be found between the urge to intervene early, with the possibility that HO may simply re-form, versus delaying surgery, which prolongs the patient’s symptoms of pain or joint stiffness, or both, with the associated functional impairments that this will cause. Moreover, waiting for a prolonged period can result in fixed contractures of the periarticular soft tissues, making restoration of movement after resection more difficult to achieve.

Classic teaching has been to wait until the HO tissue is mature, until there is no further evidence of bone formation before attempting to remove it, thus minimizing the risk for HO re-formation. This traditional approach is based on the following theoretical concept: If the bone has matured and is no longer in an active stage of formation, there will be less chance of it re-forming after the resection. Although reasonable in theory, no Level I or II studies have evaluated this concept. More recently, individual surgeons are moving to earlier resection to reduce the time of disability for the patient.⁴

The traditional methods for assessing the maturity of the HO are as follows:

Classic orthopedic texts (Level V) recommend the following approach to HO resection: Wait at least 12 to 18 months after the HO has formed to guarantee that the tissue is mature and will not reoccur. Look at the quality of the bone on radiographs to look for the features of mature bone, density, trabecular patterns of bone, and cortical maturation. Always obtain a bone scan of the area. The bone scan must be cold—that is, showing no evidence of bone turnover or overt activity, thus assuring the surgeon that the tissue is mature and not likely to return once resected. In addition, the serum ALK should be followed until it normalizes before removing the bone.^5–7

The reasons for these positions are largely anecdotal (Level V). No high level evidence exists to support any of the suggestions made in the classic literature. At best, the recommendations made are based on the clinical experience of senior authors and clinical experts in the field.

Currently, many authors believe that waiting until the radiographic appearance is reasonably mature and then proceeding with the resection is the best approach. They are hoping to reduce the morbidity of the prolonged delay to surgery and the problems of joint immobility that may not be correctable after resection. Tsionos, Leclercq, and Rochet,⁸ from the Institut de la Main, Paris, France, advised early resection in burn patients at the elbow with a suggested reduction of the period of morbidity for the patients (Level IV). Their mean time between the burn and operation was 12 months, with the median being 9.5 months. This chapter analyzes the literature according to levels of evidence to attempt to answer the question posed: When is it safe to resect HO?

EVIDENCE