Fibrodysplasia Ossificans Progressiva (FOP) Overview

• Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder marked by progressive heterotopic ossification of muscles, tendons, and ligaments.
• Research employs bibliometric and network analysis methods, using tools like Histcite, Bibexcel, and VOSviewer to map publication trends and collaborations.
• Global studies reveal distinct growth periods, landmark genetic discoveries, and evolving international collaborations that drive translational research advances.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severe genetic disorder characterized by the progressive ossification of muscle and connective tissue, leading to heterotopic bone formation, functional disability, and substantial morbidity. The distinguishing hallmark is the formation of bone in tissues such as skeletal muscle, tendons, and ligaments, which do not normally ossify. This debilitating condition has driven a focused but growing body of global research, with important advances in molecular genetics, disease registries, and translational approaches since the late 1980s (Ahmad et al., 7 Jan 2026).

1. Research Landscape and Methodological Framework

Between 1989 and 2023, FOP research has coalesced around several methodological advances in scientometrics and bibliographic analysis. The primary bibliometric study of this period utilized the Web of Science Core Collection, covering documents with search terms "Myositis Ossificans" and "Fibrodysplasia Ossificans Progressiva" in the title, abstract, or keywords. All document types meeting these criteria were included, resulting in 1,817 records (Ahmad et al., 7 Jan 2026).

Data-processing relied on Histcite for citation analysis, Bibexcel for data manipulation and co-occurrence matrices, MS Excel for descriptive statistics and trend visualizations, and VOSviewer for network visualization involving co-authorship, co-citation, and collaborative institutions. Quantitative indicators included annual publication counts, Total Local Citation Score (TLCS: citations within the FOP set), Total Global Citation Score (TGCS: citations in Web of Science at large), Total Link Strength (TLS: VOSviewer measure for collaboration and co-citation networks), and Average Citations Per Publication (ACPP) calculated as $\mathrm{TGCS} / n$.

Publication growth models were fitted using the exponential $P(t) = P_0 e^{r(t-t_0)}$, with $P_0 = 3$ in 1989 and $r \approx 9.6\%$ per annum, and also assessed by linear regression (Ahmad et al., 7 Jan 2026). Standard but not explicitly computed network centrality measures included degree and betweenness centrality.

2. Temporal Dynamics and Inflection Points

FOP research productivity exhibited distinct growth epochs. The period 1989–1998 saw slow expansion; 1999–2008, moderate growth; and 2009–2018, a rapid surge. Notable inflection points occurred around 2004 and 2009, coinciding with landmark discoveries regarding ACVR1 gene mutations and the establishment of patient registries. These milestones are temporally associated with shifts in research output and citation impact, according to both TLCS and TGCS metrics:

Period	Records	% of Total	TLCS	% TLCS	TGCS	% TGCS
1989–1993	59	3.25%	967	7.28%	1,700	3.78%
1994–1998	143	7.87%	1,716	12.92%	4,081	9.06%
1999–2003	151	8.31%	1,338	10.08%	5,209	11.57%
2004–2008	191	10.51%	2,552	19.22%	9,140	20.30%
2009–2013	294	16.18%	3,372	25.39%	9,365	20.80%
2014–2018	411	22.62%	2,678	20.17%	12,079	26.82%
2019–2023*	568	31.26%	656	4.94%	3,458	7.68%

*A citation lag underlies the lower TLCS/TGCS for 2019–2023 (Ahmad et al., 7 Jan 2026).

3. Journal Distribution and Document Typology

FOP research has been concentrated in journals specializing in bone biology, mineral metabolism, and rare diseases. The top ten outlets by publication volume and citation impact include the Journal of Bone and Mineral Research, Bone, Journal of Inherited Metabolic Disease, Clinical Orthopaedics and Related Research, and the Orphanet Journal of Rare Diseases. Among these, the American Journal of Human Genetics exhibited the highest ACPP at 48.95.

Document types by prevalence and impact:

Type	Records	% of Total	TGCS
Article	1,027	56.52%	30,851
Meeting abstract	265	14.58%	46
Review	242	13.32%	11,524
Editorial material	131	7.21%	652
Letter	76	4.18%	370
Proceedings paper	18	0.99%	25
Others	58	3.20%	614

This distribution underscores the dominance of original research articles and reviews, complemented by a smaller fraction of conference and editorial materials (Ahmad et al., 7 Jan 2026).

4. Geographical and Institutional Patterns

The United States has been the pre-eminent hub, contributing 37.31% of all publications and exhibiting the highest TGCS and TLCS, followed by the UK, Italy, Japan, and France. The top institutions include the University of Pennsylvania (14.97% of all records, leading in both TGCS and TLS), University of Liverpool, Mayo Clinic, UCSF, and University of Siena. The pharmaceutical company Ipsen also emerged among prolific contributors in recent years.

Country	Records	% of Total	ACPP
USA	678	37.31%	40.19
UK	318	17.50%	22.52
Italy	161	8.86%	19.40
Japan	126	6.93%	23.65

Collaborative strength (TLS) peaks along the USA–UK axis (2,420), with notable links to Italy (1,180) and Japan (980). Country and institutional partnership patterns indicate modular collaborative substructures, with the USA possessing degree centrality with 35 partner countries.

5. Author and Collaboration Networks

Network analytics applied via VOSviewer reveal four major author clusters, with hubs such as Kaplan FS (TLS: 14,830), Shore EM (12,250), Pignolo RJ (9,315), and Santucci A (10,084). Average cluster size is 25 authors. The co-authorship network demonstrates a density of 0.015 (1.5% of possible links), average path length of 3.2, and clustering coefficient of 0.48, characteristics of a small-world network with moderate triadic closure.

The institutional collaboration network is anchored by US and UK centers but shows emerging hubs in China and India and increasing network complexity post-2010. This suggests increasing internationalization and cross-disciplinary integration in FOP research (Ahmad et al., 7 Jan 2026).

6. Knowledge Gaps and Research Trajectories

Prominent gaps in the literature include epidemiology in Africa and South America, natural-history studies for patients over age 25, biomarker discovery for early diagnosis and flare prediction, and clinical trials for targeted small-molecule inhibitors (with only 7 imatinib case reports identified in the covered period). The post-2018 period is marked by a surge in studies on ACVR1 signaling pathway modulators, non-invasive imaging techniques, and gene-editing technologies (e.g., CRISPR/Cas9 in cellular models) (Ahmad et al., 7 Jan 2026).

Potential strategies for future research include:

• Expanding multi-center registries integrating genetic, imaging, and clinical datasets.
• Fostering industry–academia consortia for translational and clinical trial design.
• Developing international research consortia with standardized protocols and data repositories.
• Prioritizing capacity-building and exchange programs to support emerging centers, especially in underrepresented regions.

7. Strategic Recommendations and Outlook

To advance the scientific and clinical understanding of FOP, the following measures are recommended: establishment of international consortia with robust data infrastructure; targeted multidisciplinary funding; capacity-building initiatives for underrepresented geographic regions; special journal issues centering on translational and clinical discoveries; and the strategic use of network analysis indicators (TLS, centrality) to bridge peripheral and core research nodes.

The FOP research field demonstrates concentrated expertise, clear journal and institutional preferences, and evolving collaborative networks, all shaped by landmark genetic discoveries and international registry efforts. Continuing progress will depend on global collaboration, investments in epidemiological infrastructure, and translational research initiatives targeting molecular mechanisms, diagnostics, and therapeutics (Ahmad et al., 7 Jan 2026).