Radiation Oncology: A Question-Based Review

Heterotopic Ossification Prophylaxis

Jing Zeng and Michael J. Swartz

image Background

What is heterotopic ossification (HO)?

HO refers to abnl bone formation outside the −skeleton. It often appears after trauma or surgery in periarticular soft tissue and is commonly associated with injury to the hip.

What are common Sx of HO?

In HO, functional impairment such as joint stiffness is the most common Sx. Pain can also occur, beginning as early as a few days after surgery.

What is the etiology of HO?

The etiology of HO is not completely understood. It is assumed that pluripotent mesenchymal cells present in periarticular soft tissue and develop into osteoblastic stem cells, which then produce bone.

What are the highest risk factors for developing HO?

Pts who already have ipsi or contralat HO carry the greatest risk of developing further HO. Their risk is 80%–100%. Pts with osteophytes at the femoral head and socket, acetabular fractures, ankylosing spondylitis, and other hyperostosis conditions of the skeleton also carry a high risk for HO. This condition is more common in males than in females.

image Workup/Staging

How soon after surgery can radiologic evidence of HO be detected?

Radiologic evidence of HO can be detected 2–6 wks after surgery as calcified structures with blurred contours on x-ray. Bone scans typically show increased uptake in the soft tissues adjacent to the hip and can detect HO several days before it becomes apparent on plain film.

What is the most common staging system used for HO?

The most common staging system used for HO was developed by Brooker et al.

1.     Grade 1: bone islands in soft tissue around hip

2.     Grade 2: exophytes in pelvis or proximal end of femur with at least 1 cm between opposing bone surfaces

3.     Grade 3: exophytes in pelvis or proximal end of femur with <1 cm between opposing bone surfaces

4.     Grade 4: bony ankylosis between proximal femur and pelvis

5.     Grades 3–4 are considered clinically relevant even if there is no pain or impaired mobility.

image Treatment/Prognosis

What is the role of surgery in the Tx of HO?

Clinically relevant HO should be surgically removed. The risk of subsequent recurrence may be lower if the ectopic bone is removed after it has reached maturity. At the time of surgery, prophylaxis against future HO should be taken.

Other than RT, are there any other effective methods for prophylaxis against HO?

For prophylaxis against HO, indomethacin and ibuprofen (prostaglandin synthesis inhibitors) have been shown to decrease the incidence of HO compared to placebo. (Fransen et al., Cochrane Database Syst Rev 2004)

What should be the RT dose and fractionation for prophylaxis against HO?

There have been multiple randomized trials and retrospective series on the RT dose and fractionation for prophylaxis against HO:

1.     Sylvester et al. (IJROBP 1988) compared 20 Gy in 10 fx vs. 10 Gy in 5 fx, and Pellegrini et al. (J Bone Joint Surg Am 1992) looked at 8 Gy in 1 fx vs. 10 Gy in 5 fx. There were no significant differences between those doses and fractionation schemes. More recent studies looked at using lower doses.

2.     Healy et al. (J Bone Joint Surg Am 1995) compared 7 Gy × 1 against 5.5 Gy and concluded that 5.5 Gy is not a sufficient dose.

3.     Padgett et al. (J Arthroplasty 2003) looked at 5 Gy in 2 fx or 10 Gy in 5 fx. There was a trend toward increased HO of any grade in the 5-Gy group.

What is the efficacy of preop RT for HO prophylaxis compared with PORT? What are the advantages and disadvantages of preop RT vs. PORT?

In 1 study, preop RT at 7–8 Gy in 1 fx gave the same rates of prophylaxis as the same dose given postop (Gregoritch et al., IJROBP 1994). Preop RT decreases pt discomfort associated with transport and positioning for RT but is often not feasible due to scheduling issues.

How soon should PORT be given after surgery for prophylaxis against HO?

PORT prophylaxis against HO should be given no later than 4 days and ideally within 3 days of −surgery. (Seegenschmiedt et al., IJROBP 2001)

What is the time frame for giving preop RT for HO prophylaxis?

The randomized trial comparing preop RT vs. PORT for HO prophylaxis using 7–8 Gy in 1 fx (Gregoritch et al., IJROBP 1994) gave preop RT within 4 hrs of surgery. Other nonrandomized series have suggested that preop RT can be given as early as 8 hrs preop without a significant decrease in efficacy (Seegenschmiedt et al., IJROBP 2001).

Are there randomized trials comparing RT against indomethacin in HO prophylaxis?

YesBurd et al. (J Bone Joint Surg Am 2001) randomized 166 pts to rcv either indomethacin or RT postoperatively for HO prophylaxis. Grade 3–4 HO occurred in 14% of the indomethacin group as compared with 7% of the RT group, but the results were not SS (p = 0.22).

A meta-analysis by Pakos et al. (IJROBP 2004) looked at 7 randomized trials comparing RT vs. NSAIDs. They concluded that RT postop >6 Gy tended to be more effective than NSAIDs in preventing Brooker 3 or 4 HO, but the absolute difference was only 1.2%.

What is the typical RT field for HO prophylaxis?

The RT fields for HO prophylaxis typically includes the usual area at risk for HO. When treating the hip for HO prophylaxis, the cranial border is usually 3 cm above the acetabulum and inferiorly includes two thirds of the shaft of the implant. Field size is usually around 14 × 14 cm. The prosthesis may be blocked from RT if a cementless fixation is used, but observational data suggest that this blocking strategy is associated with higher rates of subsequent HO.

image Toxicity

What are the rates of increased wound-healing complications after RT for HO prophylaxis?

RT for HO prophylaxis has not been associated with an increased incidence of wound-healing −complications.

Is there an increased risk of nonfixation of cementless implants after RT for HO prophylaxis?

No. There is not an increased risk of nonfixation of cementless implants after RT for HO prophylaxis based on multiple studies (Seegenschmiedt et al., IJROBP 2001). Animal studies have shown a transient decrease in force required to remove an implant after RT, but this difference resolved by wk 3 (Konski et al., IJROBP 1990).

What is the rate of RT-induced tumor after RT for HO prophylaxis?

There has yet to be a documented case of a RT-−induced tumor after RT for HO prophylaxis. This is thought to be the effect of both low doses of RT as well as an older pt population. As RT is employed for younger pts, this concern is worth considering.