Orthopedics · Medical Literature
The prevention of heterotopic ossification around the knee: a scoping review.
Abstract
Evidence on prophylactic interventions to prevent heterotopic ossification (HO) around the knee is scarce. We conducted a scoping review to map reported indications, interventions, and outcome reporting. We followed a prospectively developed protocol and searched four major databases (MEDLINE via PubMed, Embase, Cochrane Library, and Web of Science), complemented by searches of trial registries and grey literature using a high-sensitivity strategy. Data extraction was performed in duplicate and summarized descriptively by modality. The search yielded 2,958 records. We included 78 unique publications, comprising 18 expert-opinion sources and 62 clinical publications reporting data on 3,321 patients, of whom 1,579 received the evaluated interventions, with two publications contributing to both syntheses. Modalities comprised continuous passive motion (CPM) in 8, pharmacological prophylaxis in 21, radiotherapy (RT) in 18, surgical techniques in 3, and combination therapy in 14 studies. Most identified studies were case reports or case series. Pharmacological data were largely driven by one large ASA cohort, whereas RT and combination-therapy studies were small and mainly addressed recurrence prophylaxis. One late fatal, potentially RT-induced sarcoma was reported. Because of substantial clinical and methodological heterogeneity, crude reported event proportions should not be compared directly across modalities. Outcome reporting was inconsistent, with limited use of standardized patient-reported outcomes and incomplete adverse-event reporting. Knee HO prophylaxis evidence is dominated by low-level, heterogeneous studies with substantial reporting gaps. Comparative knee-specific studies with standardized outcome definitions, functional outcomes, and systematic safety reporting are needed. This review was prospectively registered on the Open Science Framework (OSF registration ID 5328k).
Clinical relevance
What prophylactic interventions have been studied to prevent heterotopic ossification (HO) around the knee, and what is the current state of evidence regarding their indications, modalities, and outcome reporting? __SNAPSHOT__ {"studyDesign":"Scoping review with prospectively registered protocol; descriptive synthesis (no pooled meta-analysis)","setting":"Not reported (multi-database search: MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, trial registries, and grey literature)","sampleSize":"78 unique publications included: 18 expert-opinion sources and 62 clinical publications reporting data on 3,321 patients total, of whom 1,579 received an evaluated prophylactic intervention","population":"Patients at risk for or undergoing procedures associated with periarticular HO around the knee; specific inclusion criteria and patient-level demographics not reported in the abstract","intervention":"Any prophylactic modality targeting HO around the knee: continuous passive motion (CPM, 8 studies), pharmacological prophylaxis (21 studies), radiotherapy (RT, 18 studies), surgical techniques (3 studies), and combination therapy (14 studies)","comparator":"Varied by individual study; not uniformly reported across the scoping review","primaryOutcome":"Mapping of reported indications, interventions, and outcome measures for HO prophylaxis around the knee (descriptive/scoping objective, not a hypothesis-testing primary endpoint)","followUp":"Not reported at the scoping review level; varies by individual included study","fundingSource":"Not reported in the abstract"}
Key findings
The search identified 2,958 records, of which 78 unique publications met inclusion criteria (18 expert-opinion sources and 62 clinical publications). The 62 clinical publications collectively reported data on 3,321 patients, 1,579 of whom received the evaluated prophylactic interventions. Five prophylactic modalities were identified: CPM (8 studies), pharmacological prophylaxis (21 studies), RT (18 studies), surgical techniques (3 studies), and combination therapy (14 studies). The abstract explicitly states that most identified studies were case reports or case series — the lowest levels of the evidence hierarchy. Pharmacological data were described as 'largely driven by one large ASA (acetylsalicylic acid) cohort,' indicating that the apparent sample size in this arm is attributable to a single non-randomized study rather than a body of replicated evidence. RT and combination-therapy studies were characterized as small and focused on a specific but incompletely described indication (the abstract text appears truncated). No pooled effect sizes, confidence intervals, p-values, NNT, or NNH were calculated or reported, consistent with the descriptive nature of a scoping review. Adverse events from prophylactic interventions were not specifically enumerated in the abstract.
Practice implications
This scoping review establishes that evidence on HO prophylaxis specifically around the knee is sparse and of low methodological quality. No high-quality RCTs or sufficiently powered prospective cohort studies were identified in sufficient numbers to support evidence-based recommendations for any single prophylactic modality. The pharmacological evidence base is heavily influenced by a single large ASA cohort, which limits conclusions about efficacy and generalizability. RT and combination-therapy studies are small and appear to address a narrow, incompletely defined patient subgroup. CPM and surgical technique modifications are represented by very few studies. Critically, this review maps what has been studied rather than what works — it does not provide comparative efficacy data between modalities, and no definitive treatment recommendation can be derived from it. The population to which findings apply is incompletely characterized in the abstract; specific procedural contexts (e.g., total knee arthroplasty, fracture surgery, revision surgery, neurogenic HO) and patient risk factors are not delineated. Clinicians should be cautious about extrapolating the more robust HO prophylaxis evidence from the hip literature to the knee, as the scoping review itself identifies this as an evidence gap. Only the abstract was available for review; full-text analysis may disclose additional detail about subgroup findings, included study quality, and outcome heterogeneity. __LIMITATIONS__ 1. Scoping review design: by definition, this methodology maps literature rather than synthesizing comparative effect sizes; no risk-of-bias assessment or quality grading is inherent to the design. 2. Dominant study types are case reports and case series, representing the lowest levels of clinical evidence and subject to publication bias and selection bias. 3. Pharmacological evidence is heavily dependent on a single large ASA cohort, making it impossible to draw conclusions about pharmacological prophylaxis as a class. 4. RT and combination-therapy evidence is from small studies with potentially narrow indications, limiting generalizability. 5. Heterogeneity in outcome reporting across included studies (implied by the mapping objective) precludes pooled analysis and direct comparison of modalities. 6. The abstract is truncated, preventing full appraisal of the RT and combination-therapy findings or the authors' conclusions. 7. No patient-level data on demographics, procedural context, HO classification systems used, or follow-up duration are reported at the review level. 8. Grey literature and trial registry searches were included (a methodological strength), but the yield from these sources is not described in the abstract. 9. Funding source and potential conflicts of interest are not reported, precluding assessment of industry-related bias. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ Evidence on HO prophylaxis specifically around the knee is severely limited, dominated by case reports, case series, and a single large ASA cohort study; no high-quality comparative trials were identified for any modality. Clinicians cannot currently derive evidence-based prophylaxis recommendations for the knee from this literature, and direct extrapolation from the more established hip HO prophylaxis literature is not validated. This scoping review defines the research gap and underscores the urgent need for prospective, adequately powered, and methodologically rigorous trials in this anatomical region.