Heterotopic ossification (HO) is a common complication following spinal cord injuries, traumatic brain injuries and burns. Although bony overgrowth has been shown to occur after acquired pediatric amputation, there are no reports linking HO to amputation in the adult population. The authors review the literature and present a case report involving the unusual finding of heterotopic ossification following traumatic transtibial amputation in an adult patient. A 50-year-old Bosnian man sustained multiple shrapnel wounds to the lower extremities due to artillery shelling at the "Bread Line Massacre" in Sarajevo during May 1992, which resulted in bilateral transtibial amputations. One year later, with the assistance of the International Organization for Migration, he was brought to the department of physical medicine and rehabilitation at the Medical University of South Carolina for prosthetic fitting and gait training.
Roentgenograms revealed both residual limbs had developed heterotopic ossification that extended up to 4 cm beyond the tibia and fibula of the distal residual limbs into the subcutaneous tissue. The patient was fitted with bilateral patellar tendon-bearing prostheses with Springlitea dynamic response feet. Despite the presence of the extensive ossification, the patient became a successful prosthesis user and achieved independence in all activities.
Heterotopic ossification (HO) is the formation of mature trabecular bone in sites where it is not normally present. This syndrome has been associated with a number of conditions and is most commonly seen following hip surgeries, spinal cord injuries, traumatic brain injuries and burns (1).
Although bony overgrowth has been shown to occur after acquired pediatric amputation (2), no reports have linked HO to amputation in the adult population. In this article, the authors review the literature and present a case report involving the unusual finding of heterotopic ossification following traumatic transtibial amputation in an adult patient.
Heterotopic ossification is most commonly encountered following central nervous system insults (spinal cord injuries and traumatic brain injuries), traumatic violent surgical insults (total hip replacements and acetabular fractures) and burns.
Heterotopic bone formation commonly is seen following spinal cord injuries, traumatic head injuries and long-term comas. It has been described less commonly following other neurologic conditions including encephalitis (3), meningitis (4), myelitis (5), tetanus (6), tumors (7), epidural abscess (8) and subarachnoid hemorrhage (9).
Most studies report an HO incidence of 16 percent to 53 percent for spinal cord injury and 11 percent to 70 percent for traumatic brain injury (10,11). In both conditions, ossification always occurs below the level of the neurologic injury.
Several factors have been associated with heterotopic ossification following neurologic injury, including older age (12) and severity of the lesion (12,13). Patients with complete lesions are more severely affected (14). The presence of pressure sores was correlated with completeness of the lesion, which may explain the observation that pressure sores are associated with HO (15). Spasticity also is associated with ossification (14,16,17).
Traumatic HO is seen following injuries such as dislocation of the elbow, knee and hip joints or surgery typically including total hip arthroplasty and internal fixation of acetabular fractures (18). Ossification has been observed in a variety of unusual sites following localized trauma. Myositis ossificans can follow direct muscle trauma (18). Ossification of the cervix has been reported in women with a history of abortion (19). Repeated microtrauma has been implicated with ossification of the adductor longus tendon or "rider's bone" occurring in horseriders (20) and at sites of injection resulting in "drug abuser's elbow" (21).
Incidences of HO following total hip replacement and internal fixation of acetabular fractures are 8 percent to 90 percent and up to 50 percent, respectively (22-24). Factors associated with heterotopic ossification include male gender (25), pre-existing HO (25,26), osteoarthritis with osteophyte formation (25-27), decreased preoperative hip motion (28), ankylosing spondylitis (26,29) and diffuse idiopathic skeletal hyperostosis (30).
Approximately 12 percent of children with acquired amputations experience a condition known as bony overgrowth (2), which is defined as the oppositional deposition of bone to the end of the amputated long bone. This bone growth results in a spike-like formation at the end of the bone, which has a thin cortex and no medullary canal. Overgrowth is most frequently seen in the humerus, fibula, tibia and femur, in that order.
Incidence of HO with burns (1) has been reported between 0.6 percent and 23 percent. Development of HO is related to severity of the burn, immobilization of the joint and individual predisposition (1,31).
A 50-year-old Bosnian man sustained multiple shrapnel wounds to the lower extremities that ultimately resulted in bilateral transtibial amputations. Other injuries included a resolving ulnar nerve lesion and multiple shrapnel fragment wounds. These injuries occurred as a result of artillery shelling in the famous "Bread Line Massacre" at Sarajevo during May 1992 (see Figure 1) . In June 1993, with the assistance of the International Organization for Migration, the patient was brought to the department of physical medicine and rehabilitation at the Medical University of South Carolina to be fitted with prostheses and trained in their use.
Past medical history was significant for hyperglycemia and borderline hypertension. The patient did not take any medication and was allergic to penicillin.
Physical examination showed well-healed transtibial amputation residual limbs without evidence of neuromata. Both residual limbs measured 21 cm in length.
Roentgenograms taken prior to prosthetic fitting were read by a radiologist and revealed heterotopic ossification that extended up to 4 cm into the subcutaneous tissue of the distal end of the right residual limb. The tibia measured 17 cm while the fibula was 19 cm. Two ribbonlike osteophytes projected off the distal portion of the fibula, which extended about 2.5 cm from the distal portion of the tibia (see Figures 2 and 3 ). The left residual limb's tibial length measured 18.5 cm and contained heterotopic bone along its lateral portion extending 1 cm past the site of osseous amputation. The fibula measured 14 cm and also demonstrated HO extending 1.8 cm beyond the amputation site (see Figures 4 and 5 ).
The roentgenograms described above were reviewed with several orthopedic surgeons specializing in trauma. The long strands of ectopic bone noted on both fibulae were thought to possibly represent periosteal flaps that had ossified.
The patient was fitted with bilateral transtibial prostheses. The prostheses consisted of patellar tendon-bearing sockets with soft inserts and Springlite® dynamic response feet with sleeve suspension.
The patient, who was professor of mechanical engineering at the University of Sarajevo before the onset of the war as well as a father of two young sons, was extremely active and motivated. He had conscientiously performed upper-extremity resistance exercises and was remarkably well-nourished and -conditioned when he arrived and began gait training. The dynamic response feet were prescribed because of his stamina and his desire to resume his athletic lifestyle.
The patient rapidly achieved tolerance to the prostheses, and by the end of the three-week rehabilitation period, he wore them 8-10 hours daily without difficulty. The residual limbs remained nontender and without evidence of heterotopic bone eroding through the soft tissue. The patient was able to negotiate uneven terrain, stairs, curbs and ramps without difficulty. He became independent in all activities and was discharged 29 days after his admittance (see Figure 6) .
Long-term followup at three and six months after discharge found the patient working as a visiting professor at a Canadian university. He reported an active lifestyle and no problems with the residual limbs or prostheses.
The pathophysiology of HO is complex and not entirely understood. In 1975, Chalmers et al. (32) proposed three conditions necessary for heterotopic bone formation: 1) an osteogenic precursor cell, 2) an inducing agent and 3) a tissue environment permissive to osteogenesis.
Chalmers postulated the role of an osteogenic precursor cell; heterotopic ossification is thought to be the result of differentiation of noncirculating pluripotent mesenchymal cells to osteoblast stem cells. This process occurs quickly in mice, with peak activity observed at 32 hours after injury (33).
Support for the existence of an inducing agent comes from several studies. It has been shown that demineralized bone matrix can induce bone formation (34). This process was attributed to a low molecular weight (bone morphogenic) protein. Other proteins, including osteoinductive factor and osteogenin, have been isolated and shown to experimentally promote ectopic osteoinduction (35). In addition, prostaglandins have been implicated in HO (36).
Chalmers stressed the role of tissue environment in heterotopic ossification. Muscle and fascia permit experimental induction of bone while liver and kidney suppress bone formation (32). Ossification can occur following local trauma with disruption of soft tissues and periosteum (37,38), leaving bone debris, hematomas, damaged muscle and an environment of noncommitted fibroblasts. However, it also occurs in regions without obvious soft tissue damage (e.g., after neurological injury).
Although amputation leading to HO has not previously been reported in the adult population, the patient in this study possessed several of the known predisposing factors for acquiring this condition (i.e., the traumatic nature of injury and male gender).
The triggering factor for inducing HO remains unknown. In addition, the etiology for ectopic bone formation in the adult amputee is not understood and requires further investigation. As Chalmers (32) concluded, "Whether or not the tissues of the body ossify may depend on a fine balance of osteogenic and osteoinhibitory influences acting both locally and systemically." (5)