Traumatic Heterotopic Ossification Treatment & Management


Practice Essentials

Heterotopic ossification (HO) was originally described in 1692 by Guy Patin, the Doyen of the Faculté de Médecine de Paris. Patin described a condition he observed in children and called myositis ossificans progressiva. The next major development in the history of HO came in 1918 because of military injuries sustained during World War I. Dejerine and Ceillier described a condition they referred to as paraosteoarthropathy, which they observed in patients with paraplegia caused by gunshot wounds to the spinal cord.

These older terms for heterotopic ossification have been superseded, but the terms ectopic ossification and myositis ossificans are used interchangeably with the term heterotopic ossification. The condition may affect the bones or the joints. Three types of HO have been described, as follows:

  • Myositis ossificans progressiva (a rare pediatric metabolic disease whereby skeletal muscle ossifies)
  • Neurogenic HO (this occurs as a result of burns or neurologic injury)
  • Traumatic HO [12 (this follows injury to tissue surrounding the bones and joints)

Traumatic HO is the focus of this article.

Alternatively, pathologic bone formation surrounding the bones and joints can be defined histologically. HO is the formation of mature lamellar bone in nonosseous tissue, whereas myositis ossificans is a specific type of HO that occurs in inflammatory muscle. Both of these processes are examples of ectopic ossification, and they may coexist, though they are distinct from periarticular calcification, which is the deposition of pyrophosphates within the soft tissues surrounding the joints.

After arthroplasty, HO can be noted in one of two ways. The condition can be a cause of physical symptoms, notably pain and stiffness, or it  may be entirely asymptomatic and may be detected radiologically on follow-up films.

HO is seldom excised, because pain relief is often inadequate and improvement in range of motion may not last. In established cases of HO following total hip arthroplasty (THA), excision may be performed. Patients may find that their range of movement improves, but pain relief is likely to be limited. Pharmacologic agents and irradiation have been used for prophylactic purposes.

Further animal model studies are likely to provide greater understanding of HO and its management. These studies may involve research with the use of transgenic mice and bone morphogenic protein (BMP) as reliable genetic animal models. Gene and protein expression studies are likely to be required to investigate heterotopic ossification on a cellular level.

In the future, reducing the incidence of symptomatic HO may be possible and may be achieved with improved surgical techniques whereby tissue trauma is reduced and the local operative environment is less favorable to the production of heterotopic ossification.

The use of selective cyclooxygenase (COX)-2 inhibitors, with improved side-effect profiles, is likely to replace the use of nonselective agents. [345 In turn, selective prostaglandin inhibitors may replace these agents, as it seems plausible that prostaglandin E2 is important in the pathogenesis of HO. Further research is required to ascertain the role of radiation therapy in the prophylaxis of heterotopic ossification.

Anatomy

Operative treatment of HO is difficult and thus seldom performed, because pain relief is poor and improvements in the range of movement may not be sustained. Removal of heterotopic bone is technically difficult because the abnormal bone does not confine itself to the normal tissue planes. Furthermore, normal anatomic landmarks may be obscured. Consequently, to visualize the HO to excise it, an extensile surgical exposure is required.

The HO itself is typically fragile and friable and not readily removed from the soft tissues; it is embedded and blended into the soft tissues. Surgical removal may involve substantial blood loss and incomplete excision, and the risks of recurrence are high. Surgeons attempting the procedure need to be familiar with the relevant surgical approaches to the affected region and how to safely enlarge and extend the wounds.

Pathophysiology

Like the etiology (see below), the pathophysiology of HO is not completely understood. Once the osteogenic cells are stimulated, they begin to form osteoid, which in turn develops into mature HO. The underlying process is thought to be an inflammatory process in response to local tissue trauma.

BMP is believed to be important in regulating the development of HO. The heterotopic bone is known to be metabolically very active and contains more osteoblasts than ordinary bone. In addition, the tissue does not follow anatomic tissue planes and is generally more diffuse in nature than normal bone. The presence of the HO surrounding the bones and joints may affect the function of the normal soft tissues around them. Cases of HO causing ankylosis have been reported.

Etiology

The etiology of HO is, to some extent, determined by the type. The rare autosomal dominant condition myositis ossificans progressiva accounts for the inherited metabolic disease in children. Neurogenic HO may occur after head injuryspinal cord injury, infections of the central nervous system (CNS) such as tetanus and polioCNS tumorsmultiple sclerosis, and cerebrovascular accidents. Traumatic HO, the main topic of this article, can be caused by trauma (iatrogenic or other) to bones and joints.

The etiology of traumatic HO remains uncertain. During the past 50 years, a number of theories have been developed. Migrated bone marrow cells have been suggested as a potential cause of osteogenesis in connective tissue. Alternatively, muscle lesions or interstitial hemorrhagic foci have been suggested as a potential cause of muscle degeneration, perivascular connective tissue proliferation, and subsequent bone metaplasia.

A further theory has considered that periosteal damage could induce a differentiation of periarticular osteogenic cells. However, various models exist, and it is thought that the following three conditions must be met for HO to develop:

  • Osteogenic precursor cells must be present
  • An inductive stimulus should exist
  • The local tissue environment should be favorable; the osteogenic precursor cells are thought to be pluripotential mesenchymal cells that are stimulated to differentiate into osteoblasts

Epidemiology

Traumatic HO occurs in 10-20% of predisposed patients. Following THA and acetabular fracture surgery, the incidence can be 2-63%. HO apparently does not readily complicate nonoperative treatment of acetabular fractures; case series only report this complication in surgically treated cases. Implant-related series have shown an incidence of 8-90% following cementless THA, though many of the cases are asymptomatic. For distal humeral fractures and proximal humeral arthroplasty, the incidence can be 10-90%.

The incidence is the same in case series from the United States and Europe. Following total knee arthroplasty (TKA), the incidence of HO can be as high as 32%. In revision TKA, the incidence can be as high as 56%.

Bal et al examined the incidence of HO in 121 patients who underwent THA performed with a minimally invasive two-incision technique. Of the 121 patients, 32 (26.5%) developed HO, as follows: Brooker grade I, 16 patients; Brooker grade II, 9 patients; Brooker grade III, 6 patients; and Brooker grade IV, 1 patient. [6]

Some case series have suggested that HO occurring as a complication of THA tends to affect men more often than women (perhaps as much as a 3:1 male-to-female ratio), and it is more likely to occur if osteophytosis was a feature of the underlying degenerative joint disease. Other case series have shown that although men tend to be affected more often than women, women with HO experience more pronounced symptoms.

Prognosis

If HO is excised, improvements in functional range of movement can be expected, though they may not last, and those patients who have pain from the HO may not have complete resolution of these symptoms. Alkaline phosphatase levels may be used to indicate osteoblastic activity and can be used to assess the development of HO in the postoperative phase.

The results of one study concluded that regardless of etiology, significant gains in range of motion are achieved with surgical excision of heterotopic bone around the elbow. A higher recurrence rate was observed in patients with CNS injuries as compared with patients with localized trauma.



History and Physical Examination

After arthroplasty, heterotopic ossification (HO) can be noted in either of the following two ways:

  • The condition can be a cause of physical symptoms, notably pain and stiffness
  • The condition may be entirely asymptomatic and may be detected radiologically on follow-up films

A person who has symptomatic HO may present with a loss of range of movement in the affected joint. This may coexist with pain and soft-tissue swelling. Differential diagnoses of this clinical picture would include the following:

Complications

HO may cause pain and stiffness. In turn, joint stiffness may cause further contractures. In severe cases, joint ankylosis may result. Nerve entrapment across joints also may be a complication of HO. Rare cases of HO undergoing malignant sarcomatous change have been reported.



Laboratory Studies

Alkaline phosphatase (ALP) levels can be used to evaluate heterotopic ossification (HO). If the serum ALP level is raised, inorganic phosphate should be assayed because this level should also be raised and accompanied by a transient decrease in serum calcium level. The ALP level may be as high as three to four times the normal level, peaking at about the 12-week stage. A prolonged increase in the ALP level can be of prognostic value because this may indicate ongoing osteoblastic activity.

Plain Radiography

Plain radiographs are useful in the diagnosis of HO. The appearance of the hip is classified according to the Brooker grading system (see the images below), [8 which makes use of the following four grades:

  • Grade I - Appearance of islands of bone within the tissues
  • Grade II - Spurs of bone emanate from either the femur or the pelvis, with gaps of more than 1 cm between these spurs
  • Grade III - Gaps between spurs are less than 1 cm
  • Grade IV - Apparent ankylosis of the hip caused by the HO
Brooker I heterotopic ossification associated withBrooker I heterotopic ossification associated with an uncemented total hip arthroplasty.
Brooker I heterotopic ossification associated withBrooker I heterotopic ossification associated with a cemented total hip replacement that has undergone acetabular component augmentation and fixation of the greater trochanter.
Brooker I heterotopic ossification associated withBrooker I heterotopic ossification associated with a revision hip arthroplasty.
Brooker I heterotopic ossification associated withBrooker I heterotopic ossification associated with bilateral revision hip arthroplasties.
Brooker II heterotopic ossification associated witBrooker II heterotopic ossification associated with a right cemented total hip replacement. On the left side, an uncemented total hip arthroplasty is present with no heterotopic ossification.
Brooker II heterotopic ossification associated witBrooker II heterotopic ossification associated with a right revision hip arthroplasty.
Brooker III heterotopic ossification associated wiBrooker III heterotopic ossification associated with a left uncemented total hip arthroplasty.

An alternative grading system was developed by Schmidt and Hackenbroch that is more complex than the Brooker system. [9 This system classifies HO according to its location or region (by number) and extent (by letter), as follows:

  • Region I - HOs are strictly below the tip of the greater trochanter
  • Region II - HOs are below and above the tip of the greater trochanter
  • Region III - HOs are strictly above the tip of the greater trochanter
  • Grade A - Single or multiple HOs are less than 10 mm in maximal extent without contact with the pelvis or the femur
  • Grade B - HOs are greater than 10 mm without contact with the pelvis but with possible contact with the femur; there is no bridging from the femur to the proximal part of the greater trochanter and no evidence of ankylosis
  • Grade C - Ankylosis by means of firm bridging from the femur to the pelvis is present

Other Imaging Studies

It takes approximately 2 weeks before sufficient mineralization from HO is detectable on plain films. Computed tomography (CT) or bone scanning may detect this condition sooner. In early HO, bone scans may demonstrate abnormalities on the blood-pool phase and reflect the hypervascularity of the lesion.

The hypervascularity may also be noted on angiography performed early in the natural history of the condition. In mature HO, angiography is of limited use because the lesion becomes avascular.

Ultrasonography (US) has also been suggested as a potentially useful modality for quantitative evaluation of HO during rehabilitation after trauma. [10]

Histologic Findings

Within 1 week of the index trauma, HO commences with a spindle-cell proliferation. Within a few days of the spindle-cell proliferation, peripheral primitive osteoid develops. About 2 weeks after the index trauma, primitive cartilage and woven bone develop. Trabecular bone begins to appear 2-5 weeks after the index trauma. If a biopsy is performed on HO at 6 weeks after the index trauma, specimens reveal immature undifferentiated tissues centrally with mature lamellar bone peripherally, a finding known as the zonal phenomenon.


Surgical Therapy

Heterotopic ossification (HO) is seldom excised, because pain relief is often inadequate and improvement in range of motion (ROM) may not last. In established cases of HO following total hip arthroplasty (THA), excision may be performed. [11The results of this procedure are varied. Patients may find that ROM improves, but pain relief is likely to be limited.

After trauma to the elbow, surgical excision may be indicated on the basis of pain, nerve entrapment, and stiffness. In such cases, the surgical procedure may be beneficial in that associated contractures are released, and this release can be as important as removal of the HO. [12The timing of surgery is controversial. HO is often thought to take approximately 12 months to mature; however, surgical treatment of posttraumatic HO at the elbow has been performed effectively at 3 and 6 months post trauma. [1314]

The pearls for surgical treatment of HO are as follows:

  • Handle tissue carefully
  • Avoid excess bleeding
  • Achieve good hemostasis
  • Beware of lesions that span internervous tissue planes

Because removal of HO may involve substantial blood loss and excision may be incomplete, and because the risks of recurrence are high, surgeons attempting surgical removal of HO need to be familiar with the relevant surgical approaches to the affected region and to know how to enlarge and extend the wounds safely.

A definitive list of surgical contraindications for surgical excision of HO has not been established. However, excision should not be performed before the HO has matured, because incomplete and inadequate excision may result. Surgery on a joint that has wound sepsis or deep sepsis is contraindicated because the outcome is likely to be suboptimal.

Because the outcome of surgery is unpredictable, the indications must be considered carefully. Pain relief cannot be predicted reliably after excision of HO as a complication of THA, whereas better results for improved ROM arcs are more likely.

Activity

Depending on where the ROM in the joints is impaired following arthroplasty as a result of HO, outpatient rehabilitation physiotherapy and hydrotherapy may be useful. The nature of the physiotherapy used for treatment is controversial. Forceful manipulation can be detrimental because the trauma involved can increase the development of HO. Physiotherapy that involves passive and active elements to maintain and increase ROM in the affected joints can be beneficial.

Prevention

Traumatic HO can be treated in a number of ways. In the case of iatrogenic surgical trauma, prevention of the formation of HO should be considered the index treatment.

Modification of risk factors

A number of risk factors can be considered important in the pathogenesis of types of acquired HO:

  • Trauma
  • Burns
  • Neurologic injury
  • Previous HO
  • Previous resection of HO
  • Hip and pelvic surgery
  • Previous hip surgery sepsis
  • Revision surgery
  • Reoperation upon an existing arthroplasty
  • Reimplantation following an excision arthroplasty
  • Male sex
  • Advanced age (>60 years)
  • Genetic predisposition (possible)

Furthermore, patients who have conditions such as diffuse idiopathic skeletal hyperostosisPaget disease, a preexisting hip fusion, posttraumatic arthrosis, hypertrophic osteoarthritis, or ankylosing spondylitis may be more likely to develop HO as a complication of THA. Children with cerebral palsy who undergo hip soft-tissue releases or spinal surgery are thought to have an increased risk of developing HO.

Risk factors that are related to surgical technique and therefore are potentially modifiable are as follows:

  • Prolonged surgery
  • Presence of pressure sores near the surgical field
  • Amount of bone resected
  • Amount of soft tissue dissected
  • Muscle ischemia
  • Tissue trauma
  • Bone trauma
  • Persistence of bone debris (reamings, marrow, or dust within the surgical field)
  • Prolonged soft-tissue retraction
  • Presence of devitalized tissue
  • Presence of hematoma
  • Postoperative wound infection
  • Prolonged postoperative wound drainage

Some case series have shown that factors such as the lateral approach to the hip, the use of cementless components, and the use of a trochanteric osteotomy may increase the risk of HO in THA, but these factors for increased risk are by no means certain. A meta-analysis by Zhu et al identified the following as risk factors for HO after THA [15:

  • Male gender
  • Cemented implant
  • Bilateral operations
  • Ankylosing spondylitis
  • Ankylosed hip

A patient with HO following THA is thought to have a 90-100% chance of developing it on the contralateral hip if this hip also undergoes THA. Consequently, certain patients with preexisting risk factors could conceivably be regarded as high-risk and be treated with a more intensive prophylaxis regimen than the standard one, though this may not be practical. Nevertheless, it would be prudent to minimize the risk of HO developing after arthroplasty by performing surgery whereby the following are ensured:

  • Exposure is meticulous
  • Retraction is performed carefully and soft tissue is handled carefully
  • Irrigation is adequate
  • Devitalized tissue is excised
  • Hemostasis is adequate
  • Postoperative drains (when used) are not retained for longer than necessary
  • Perioperative antibiotic prophylaxis is used
  • Postoperative anticoagulation (when used for deep vein thrombosis prophylaxis) is carefully controlled

A systematic review of 45 studies by Liu et al, which included 2256 patients who underwent total elbow arthroplasty (TEA), found that the literature did not support routine HO prophylaxis for TEA and noted that the effectiveness of prophylaxis in high-risk patients was uncertain and in need of clarification. [16]

Pharmacologic prophylaxis and localized radiotherapy

After procedures that may be complicated by HO, recommendations indicate that prophylaxis should be given in the form of nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, or aspirinlike drugs that act as nonspecific cyclooxygenase (COX) inhibitors. [1718The duration of treatment is controversial. Some studies have shown that treatment should continue for 6 weeks after the procedure; others have suggested that it need only be continued for 20, 14, or 7 days after the procedure. Bisphosphonates are ineffective in the prophylaxis of HO.

An alternative or possible adjunct to COX inhibition is the use of localized irradiation. [19However, clinical evidence suggests that localized irradiation is not better than indomethacin alone for HO prophylaxis following surgery of acetabular fractures. Some clinicians would advocate the use of adjuvant radiation therapy in the prophylaxis of HO in individuals considered to be at high risk (defined as a ≥50% chance) for this condition.

The irradiation protocol is controversial. Radiation therapy may be effective if given up to 24 hours preoperatively or within 72 hours postoperatively. However, it is unclear whether an optimal time to apply the treatment dose exists within these differing schedules. Randomized trials have shown that single fractions are as effective as multifraction schedules. Debate exists regarding the irradiation dosage. Some studies indicate that 7 Gy may be more effective than 5.5 Gy as a single dose; others recommend 8 Gy or 12 Gy doses as single fractions or multifraction regimens.

The role of radiation therapy in HO prophylaxis is not fully defined, and because its logistic availability is limited, its use will continue to be selective rather than widespread.

Pakos et al evaluated the efficacy of combined radiotherapy and indomethacin against that of indomethacin alone for prevention of HO after hip arthroplasty in 96 patients, who received either a single dose of postoperative radiotherapy of 7.0 Gy and indomethacin for the first 15 postoperative days or indomethacin alone for the same period. [20A historical group of 50 patients who received indomethacin alone served as the control group.

In this study, four patients in the combined-therapy group developed HO, compared with 13 patients in the indomethacin group and 13 in the control group. [20One patient in the combined-therapy group and one in the control group developed Brooker III HO. Duration of surgery and congenital hip disease were associated with HO development in the indomethacin groups; in the combined-therapy group, age and congenital hip disease were associated with HO.

Prophylaxis using NSAIDs may be complicated by the adverse effects of these drugs. Radiation therapy complications may also occur if this approach is used for prophylaxis. However, the exact incidence of these complications is not known. Long-term follow-up studies to detect late complications are lacking. A case-control analysis by Sheybani did not demonstrate any increase in the risk of radiation-induced malignancy in patients who received radiation therapy as prophylaxis for HO.


0 comments:

Post a Comment