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Heterotopic Ossification

Treatment of Heterotopic Ossification

The published literature on treatment of HO provides evidence for non-steroidal anti-inflammatory drugs, warfarin, bisphosphonates, pulse low-intensity electromagnetic field therapy, radiation and surgical excision.

Author(s); Country
Date included in the review
AMSTAR score
Number of articles
Method:
Level of evidence
Questions
Conclusions
Yolcu et al. 2020b; USA
Review and meta-analysis of published articles until December 20, 2018
N=5

Method: Comprehensive literature search of English RCT and observational studies directly comparing prophylactic
medication to a placebo for prevention of HO following SCI in adult age group (≥18 yr). A meta- analysis comparing the incidence of HO between the two groups was conducted, with a subgroup analysis of non-steroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs.
Databases: EBM, Embase, Ovid Medline, Scopus, Web of Science
Level of Evidence: According to the Cochrane Collaboration for assessing risk, the two RCTs showed low risk. The observational studies scored between 7–8 on the Newcastle-Ottawa Scale (NOS), indicating high quality of evidence. Confidence in estimates was high for both overall HO and NSAIDs subgroup, while non-NSAIDs was ranked low due to inconsistency in reporting as well as the large CI.
Questions/measures/hypothesis: Assess the preventive efficacy of prophylactic medications on heterotopic ossification after SCI compared to placebo.

  1. Overall incidence of HO was 9.73% in the medication group versus 16.5 % in the placebo group, although the difference is not statistically significant (p=0.21).
  2. In the subgroup analysis for NSAIDs, those who received prophylactic treatment with NSAIDs had a lower incidence of HO compared to those who received placebo (p=0.003).
  3. As for studies that used bisphosphonates, a significant difference in incidence of HO was not found (p=0.58) and the overall evidence was inconclusive.
Aubut et al. 2011; Canada
Review of published articles between 1980-2010
AMSTAR=8
N=26
Method: Comprehensive literature search of English RCT, Cohort studies, case series, and review articles of traumatic SCI in adult age group (≥18 yr).
Databases: MEDLINE, EMBASE, CINAHL, PsycInfo.
Level of evidence: Moderate quality: Downgraded high quality studies, non-randomized trials, prospective cohort studies; Low quality: Retrospective observational, retrospective cohort and case-control studies; Very low quality: Case series, case reports, reviews and others.
Questions/measures/hypothesis: Examine the effectiveness of pharmacological, non-pharmacological and surgical management of HO after ABI and SCI.
  1. ABI population usually required multicomponent treatments compared to the SCI population.
  2. There are more level 1 and level 2 evidence for the SCI literature in supporting HO treatment, while the literature for the ABI population is weaker with mainly level 4 evidence.
  3. HO in SCI patients was mostly seen in the hip while the ABI patients had more varied location of HO including hip, knee and elbow.
  4. Etidronate and indomethacin post-surgery suggested for both populations to reduce the risk for HO.
Teasell et al. 2010; Canada
Review of published articles between 1980-2009
AMSTAR=8
N=13
Method: Comprehensive literature search of English RCT, Cohort studies, case series, and review articles of traumatic SCI in adult age group (≥18yr).
Databases: MEDLINE, EMBASE, CINAHL, PsycInfo.
Level of evidence: Moderate quality: Downgraded high quality studies, non-randomized trials, prospective cohort studies; Low quality: Retrospective observational, retrospective cohort and case-control studies; Very low quality: Case series, case reports, reviews and others.
Questions/measures/hypothesis:Examine the effectiveness of pharmacological, non-pharmacological and surgical management of HO after SCI.
  1. There was strong evidence that early prophylactic treatment was efficacious in preventing HO, in which NSAIDs showed greatest effectiveness (level 1 evidence).
  2. Bisphosphonates had the strongest evidence for treatment of HO (level)
  3. There is some evidence for the use of Pulse low intensity electromagnetic field therapy (PLIMF), however, further research is needed.

Three systematic reviews examined the effectiveness of HO management interventions. Aubut et al. (2011) found that pharmacological interventions were effective in the prophylaxis of HO. Teasell et al. (2010) also found that rofecoxib and indomethacin were effective in preventing HO after SCI. However, only limited evidence supported the use of radiotherapy, warfarin, or Pulse low intensity electromagnetic field therapy (PLIMF) for the prevention of HO after SCI. Once HO developed, only surgical resection was found to be effective, while bisphosphonates such as Etidronate Disodium and pamindronate were supported by limited evidence. Finally, Yolcu et al. (2020b) conducted a systematic review and meta- analysis comparing prophylactic medications to placebo for prevention of HO post- SCI. Although the overall analysis did not indicate a statistically significant benefit to use of prophylactic medication to prevent HO as compared to placebo, when only analyzing NSAIDs, patients who received prophylatic NSAIDs showed significantly lower incidence of HO. The authors pointed out that while promising for secondary prevention of HO among patients with SCI, further prospective studies with longer follow-ups are needed to explore other appropriate medications for HO prevention (Yolcu et al., 2020b).

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