Bone Scintigraphy for Evaluation of Heterotopic Ossification in Patients with Spinal Cord Injury

Gabriel Soudry, M.D.

David E Drum, MD

December 7, 1993

Case Presentation:

A 20-year-old white male became quadriplegic after a diving accident 8 weeks before presentation. He was referred to nuclear medicine for evaluation of pain, erythema swelling and hardness in both lower thighs with restriction of knee motion.

Findings:

A three phase bone scan, performed as part of the work-up, showed increased flow, increased blood pool (23k bytes), and increased activity on 3 hour delayed images (36k bytes) consistent with deposition of calcium in the soft tissues of the lower thighs see on X-ray (right (77k bytes) and left (90k bytes)). The activity in regions-of-interest (32k bytes) over the right (1) and left (2) knee were compared to the activity in a region over the L4 region (3). The patient was started on disodium etidronate. A follow-up bone scan done three months later showed increase in the degree of uptake in both knees consistent with active heterotopic ossification (HO).

       Baseline  3 Months
R knee    8.5      11.2
L knee    8.8      10.4
L4        1.0       1.0

Discussion:

Heterotopic ossification is a phenomenom in which new bone is formed in tissue that do not normally ossify. This process differs from dystrophic calcification in soft tissue, where no osteoblastic activity exists. The entity, heterotopic ossification, is also referred to as paraosteoarthropathy (POA), ossifying fibromyopathy, myositis ossificans, and ectopic ossification.

There is considerable uncertainty about the etiology of heterotopic ossification. With appropriate stimulation the pluripotential stem cells present in soft tissues can differentiate along collagenoid, chondroid or osteoid lines. The nature of the stimulus in spinal cord injury is unknown (1).

Heterotopic ossification is the associated with many other disease entities and various forms of trauma including head injury, and traumatic or surgical insult.

The prevalence of heterotopic ossification in spinal cord injury patients is reported to be 10%-25%. The most commonly involved joint is the hip followed by the knee. Heterotopic ossification rarely affects the upper extremity (2).

When the extent of heterotopic ossification is of such magnitude that limitation of joint motion occurs, heterotopic ossification may interfere with activities of daily living such as sitting and dressing of the lower extremities or cause abnormal skin pressure areas. Neurovascular compression has also been reported (3). Ankylosis occurs in 5% of the cases (4).

The clinical signs and symptoms of acute heterotopic ossification include pain, fever, local swelling/erythema/warmth, stiffness/loss range of motion. Such features often result in an incorrect initial diagnosis of thrombophlebitis, cellulitis and osteomyelitis. In the chronic and stable stage, pain and limited range of motion are the main manifestations.

The laboratory evaluation may show an increase in serum alkaline phosphatase.

On plain radiographs, the appearance of heterotopic ossification varies from hazy calcific areas to dense masses.

The earliest finding on bone scan is increased blood flow and blood pool in the regions of heterotopic ossification, followed by soft tissue localization on the 3 hour delayed scan.

Disodium etidronate is the only drug shown to alter the formation of heterotopic ossification but it does not prevent the formation of an osteoid matrix. When treatment is discontinued, mineralization occurs (2).

The timing of surgical resection is important because the heterotopic ossification must be mature to minimize postoperative recurrence (4). The time elapsed from injury, the serum alkaline phosphatase level and the radiographic appearance are inadequate to confirm maturity (2,1,5).

The incidence of perioperative complications is very high and includes excessive bleeding, fractures and infections (2,4). These emphasize the need for a good indicator of heterotopic ossification maturity.

In addition to providing a sensitive tool for early diagnosis of heterotopic ossification, serial bone scanning (5) allows the observer to follow heterotopic ossification/normal bone activity ratios. A continuing decreasing trend of this ratio or a steady state suggests maturation. However, the initial description of this method by Tanaka and collaborators was based on only three observations. Since then, it appears no large prospective or even retrospective study correlating heterotopic ossification maturity with incidence of heterotopic ossification recurrence after surgery is available.

In a series of 19 patients with pre-operative bone scans, Garland had 2 significant recurrences in 7 hips with chronic mature ossification (28%), and 5 recurrences in 9 hips with chronic active maturing ossification (55%) (5). In another series of 18 patients, Stover found " little correlation " between the extent of recurrence and the maturity rating scale. However preoperative bone scans were not done on all of the study patients and no numbers on the maturity ratios were available (4).

Conclusions:

Three phase bone scan appears to be an excellent tool for early detection and subsequent evaluation of heterotopic ossification.

Prospective studies are needed to evaluate the clinical utility of serial quantitative bone scans for judging disease activity and in predicting postoperative recurrence of heterotopic ossification.

References:

1.Cope, R. Heterotopic ossification. South Med J 1990; 83(9): 1058-64.

2. Garland D. A clinical perspective on common forms of acquired heterotopic ossification. Clinic Orthop. 1991; (263):13-29. 3.Colachis S, Clinchot D, Venesy D. Neurovascular complications of heterotopic ossification following spinal cord injury. Paraplegia 1993; 31(1):51-7.

4. Stover S, Kurt M, Niemann W,Tulloss R. Experience with surgical resection of heterotopic bone in spinal cord injury patients. Clinic Orthop. 1991;(263):71-77.

5. Garland D, Orwin JF. Resection of heterotopic ossification in patients with spinal cord injuries. Clinic Orthop. 1989;(242):169-176.

6. Tanaka T, Rossier A, Hussey R, Ahnberg D,Treves S. Quantitative assessment of para-osteo-arthropathy and its maturation on serial radionuclide bone images. Radiology 1977; (123):217-221.

7.Orzel J, Rudd T. Heterotopic bone formation: clinical, laboratory and imaging correlation.J Nucl Med. 1985; (26):125-132.

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu