Table 3.

Treatment of Heterotopic Ossification Post SCI

Study	Eligibility criteria	Methods	Outcome Measures	Results
Bisphosphonates
Etidronate
Banavac et al., 199325 USA D&B=12	Inclusion: No specific inclusion criteria listed. Patients with SCI admitted to the rehabilitation center 2–6 weeks post injury. There were 2 females and 25 males, ranging in age from 16 to 54 years, who were either paraplegics or tetraplegics. Exclusion: Not specified.	Prospective control trial - 27 patients participated. 300mg etidronate disodium was administered IV over a 3-hour period daily for 3–5 days. After parenteral therapy, 20 mg of etidronate was administered orally for 6 months. 11 controls received oral etidronate alone for 6 months.	Observed swelling.	After initial IV therapy, 20 patients showed prompt reduction in swelling over initial 48 hrs, while 7 patients had no change or an increase in swelling. Overall, treatment reduced swelling (p<0.01). No significant differences noted between those who had received both IV and oral etidronate and those who had received oral etidronate alone, with respect to effect on HO.
Garland 198327 USA D&B=9	Inclusion: Spinal cord injured patients with clinical signs of HO. Mean age = 25y; Gender: males = 9; Level of injury: cervical = 6, thoracic =5; Severity of injury: complete = 7, incomplete = 2; Etiology of injury: diving accident = 3, motor vehicle accident = 1, gunshot wound = 1, motorcycle accident = 1, hand-gliding accident = 1. Exclusion: Not specified.	Case series - 14 patients participated. Once HO was diagnosed in patients, bisphosphonate therapy was administered at a dosage of 20mg/kg/day for two weeks and then at a dosage of 10mg/kg/day for 2 years.	Effectiveness of treatment, adverse effects	Pre-treatment 8/9 patients had HO in 10 hips. The 9th patient had a positive bone scan but no radiographic evidence of HO. Post treatment all patients showed evidence of HO. Post-treatment of the 9 minimal graded hips only 1 stayed at the minimal grad while others increased (5 mild, 3 moderate, 5 severe). No adverse effects were seen.
Subbarao et al., 198728 USA D&B=8	Inclusion: Specific inclusion criteria not listed; however, participants were between the ages of 34 and 41years, and were 77 to 197 months post injury; duration of follow-up ranged from 8 to 35 months. Exclusion: Not specified.	Case Series - etidronate (20mg/kg body weight) was given 10–14 days preoperatively; medication was withheld for a postoperative period of 72 hours, but then continued (10mg/kg body weight) for a minimum of 3 months. All 5 patients underwent wedge resection at hip to permit free movement of hip in flexion.	Not specified.	At last follow-up, all patients were able to function independently in their wheelchairs, except for one who functioned independently in a semi-reclining wheelchair. Patients had severe restriction of ROM in involved joints.
Banavoc et al., 199724 USA D&B=7	Inclusion: Not explicitly stated. A likely diagnosis of HO based upon clinical signs and symptoms and positive bone scintigraphy in SCI patients. Those who participated were admitted to the rehabilitation centre 2 to 5 weeks post injury, and ranged in age from 16 to 55 years. Two were female and 44 were male. 24 patients were paraplegic and 22 were tetraplegic Exclusion: Not specified.	Prospective control trial - 46 patients participated. 3 hrs of IV disodium etidronate on day of HO diagnosis, continued for 3 successive days, followed by etidronate X6 mos.	Degree of HO was determined radiographically: Grade 1 = minimal, Grade 2 = mild, Grade 3 = moderate, Grade 4 = severe, Grade 5 = ankylosis.	Group 1 (positive bone scan and negative X-ray for HO, n=33), 5 patients discontinued therapy and showed gradual development of HO. Of the remaining 28 patients, 22 had no X-ray evidence of HO, while 6 had developed an X-ray diagnosis of HO at follow-up. Group 2 (positive bone scan and X-ray, n=13). Progression of soft tissue ossification was inhibited by etidronate in 1 of 6 patients, while the remaining 7 did not respond to treatment, with progression of HO.
Banovac 200026 Denmark D&B=7	Inclusion: No specific inclusion criteria listed; however, participants had been admitted to the rehab center 2 to 5 weeks post injury. 39 males and 1 females; mean age 23 years. 18 with tetraplegia and 22 paraplegia. Exclusion: Not specified.	Case series - 40 patients with positive clinical findings and positive nuclear bone scan were treated with IV etidronate sodium, followed by 20mg/kg/day given orally for 6mos.	Not specified.	11/40 (28%) SCI patients developed radiographic evidence of HO from 1.5 to 6yrs post treatment. 95% of cases of recurrent HO developed in different areas, involving different joints.
Pamidronate
Schuetz et al., 200529 Switzerland D&B=9	Inclusion: No specific inclusion criteria stated; however, all were male and between the ages of 47 and 68 years. Exclusion: Not specified.	Case study - 5 patients underwent excision-surgery for removal of HO. Pamidronate administered IV peri- and post-op, starting at 120 mg for 1st 12 hrs, gradually increasing dose over a total of 6–14 days.	Not specified.	None of the patients treated with pamidronate exhibited clinical, X-ray or lab signs of HO recurrence or new HO at time of follow-up, 5–54 months post-op.
Radiotherapy
Sautter-Bihl 200132 Germany D&B=12	Inclusion: SCI patients showing primary clinical signs of HO between December 1989 and March 2000 were included. Mean age = 33y; Gender: males = 44, females = 8. Exclusion: Not stated.	Case Series - 52 patients. Radiotherapy was used to treat HO and manifestation of heterotopic bone formation after resection in SCI patients. A linear accelerator at 6 to 8 MV photons with single doses between 2 to 10 Gy was used.	Efficacy, Brooker score, adverse effects	Prevention of HO was seen in 71% (41 primarily treated and 9 resected) of joints. Radiotherapy treatment did not result in a regression of the Brooker score in any patient. An increase in two Brooker score grades was seen in two joints (1 knee, 1 hip). No adverse effects due to therapy occurred.
Sautter-Bihl et al., 200033 Germany D&B=9	Inclusion: Although no specific inclusion criteria were stated, participants were between the ages of 17 and 59 years, and duration of follow up was 4 to 98 months. Exclusion: Not specified.	Case series- 25/36 patients received 10 Gy in increments of 2–2.5Gy, while 4 patients received higher doses. In Phase 2, 7 patients received a single dose of irradiation with 8Gy. In total, 46 joints were irradiated in 36 patients.	Not specified.	16 of the 32 hips treated with radiotherapy only (50%) did not show any abnormalities on follow-up. No progression of HO was noted in 30/36 subjects (83%). Re-ossification after therapy, which led to a decrease in joint mobility, was noted in 3 subjects.
Excision
Garland &Orwin 198935 USA D&B=14	Inclusion: No specific inclusion criteria were listed. Participants were individuals with SCI with mean age=22.5y; Level of injury: paraplegia=8, tetraplegia=11. Severity of injury: complete=12, incomplete=7. Exclusion: Not specified.	Case series: Records of 19 SCI individuals who underwent hip resection for HO between 1970 and 1985 were reviewed.	Range of motion, re-occurance rate, adverse effects.	13 of 24 hips operated on had similar or less motion when compared to preoperative motion, 15 had 10 – 39 degrees improvement, and 6 had greater than 40 degrees improvement. 2Total recurrence rate was 92% (22 of 24 hips). 3A high number of complications, infections and blood loss were present.
Meiners et al 199734 Germany D&B=12	Inclusion: Specific inclusion criteria not listed; however, participants had a mean age of 37.87y; males = 28, females = 1. Exclusion: Not specified.	Case Series - Resection of HO of the hip via ventral approach. Post-operation: Wk 1 – irradiation of hip with a linear accelerator; Day 15 – passive movement exercises implemented.	Range of motion (ROM) – flexion & extension; pre-operatively, post-operatively, intra-operatively & at follow-up.	4Mean ROM pre-operatively = 21.95°. 5Mean ROM intra-operatively = 94.51°. 6Mean ROM at follow-up (M=4.2yrs) = 82.68°.
Schuetz et al., 200529 Switzerland D&B=9	Inclusion: No specific inclusion criteria stated; however, all were male and between the ages of 47 and 68 years. Exclusion: Not specified.	Case study - 5 patients underwent excision-surgery for removal of HO. Pamidronate administered IV peri- and post-op, starting at 120 mg for 1st 12 hrs, gradually increasing dose over a total of 6–14 days.	Not specified.	None of the patients treated with pamidronate exhibited clinical, X-ray or lab signs of HO recurrence or new HO at time of follow-up, 5–54 months post-op.
Subbarao et al., 198728 USA D&B=8	Inclusion: Specific inclusion criteria not listed; however, participants were between the ages of 34 and 41years, and were 77 to 197 months post injury; duration of follow-up ranged from 8 to 35 months. Exclusion: Not specified.	Case Series - etidronate (20mg/kg body weight) was given 10–14 days preoperatively; medication was withheld for a postoperative period of 72 hours, but then continued (10mg/kg body weight) for a minimum of 3 months. All 5 patients underwent wedge resection at hip to permit free movement of hip in flexion.	Not specified.	At last follow-up, all patients were able to function independently in their wheelchairs, except for one who functioned independently in a semi-reclining wheelchair. Patients had severe restriction of ROM in involved joints.

Abbreviations: D&B, Downs and Black quality assessment scale score²⁰, HO. heterotopic ossification; IV, intravenously; ROM, range of motion; SCI, spinal cord injury.