Pharmacological interventions for treating acute heterotopic ossification
Abstract
Background
Heterotopic ossification (HO) is the formation of mature lamellar bone in soft tissue sites outside the skeleton. HO frequently complicates burns, arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint function.
Objectives
To determine the efficacy of medications to treat acute HO on radiological, symptomatic, functional impairment, and disability outcomes.
Search methods
We searched the Cochrane Bone, Joint and Muscle Trauma Group specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to August 2004), CINAHL (1982 to August 2004), other databases, reference lists of articles, and contacted trialists and drug companies. No language restrictions were applied.
Selection criteria
All randomised or quasi‐randomised controlled trials that assessed the efficacy of any medication for treating acute HO (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and which used radiography to grade post‐treatment HO severity.
Data collection and analysis
Two reviewers independently assessed the study quality and extracted data. We analysed two dichotomous outcomes: no progression in HO grade (versus progression) and improvement in HO grade (versus no improvement).
Main results
Two randomised trials comparing disodium etidronate versus placebo were included (Ono 1988; Stover 1976), from which ninety‐two participants with spinal cord injury had radiographically‐proven HO at baseline. At the completion of the 12 week intervention, the Ono study but not the Stover study, suggested that disodium etidronate was associated with a significantly greater likelihood of successfully preventing the progression of radiographic HO grade, (relative risk (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78 to 2.84 respectively) and a significantly greater likelihood of improvement in HO grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53 respectively). There was evidence of statistical heterogeneity for the latter outcome. Longer term radiographic, clinical or side effect outcomes were unavailable. Data was not pooled due to this heterogeneity and the inadequate duration of follow up.
Authors' conclusions
Given the absence of long term radiographic outcomes in the included studies, there is insufficient evidence to recommend the use of disodium etidronate or other pharmacological agents for the treatment of acute HO. It has been previously suggested that disodium etidronate acts by delaying, rather than preventing, the mineralization of HO, and that mineralization may occur after treatment cessation in many cases, thereby negating the benefit of disodium etidronate on eventual HO grade. Further studies are required to assess all pharmacological treatments for acute HO with sufficient follow‐up duration.
PICOs
Plain language summary
Pharmacological interventions for treating acute heterotopic ossification
Abnormal bone formation in soft tissues occurs frequently after burns, joint replacements, fractures, and spinal cord and brain injuries, predominantly in the region of large joints. Limiting the extent of abnormal bone formation could reduce its potential to affect joint function. Any future use of medications for the acute treatment of abnormal bone formation should be within the setting of a randomised controlled trial.
