Fracture risk in Ehlers Danlos Syndrome

Fracture Risk in Ehlers-Danlos Syndrome: A Review of Current Evidence and Clinical Implications

Pradeep Chopra, MD, MHCM

Abstract

Ehlers-Danlos Syndrome (EDS) is a group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Recent studies suggest that individuals with EDS may also experience an increased risk of bone fractures, though the mechanisms and extent vary by subtype. This review examines the current evidence linking EDS to fracture risk, explores contributing factors such as reduced bone mineral density (BMD), joint instability, and altered biomechanics, and highlights considerations for clinical management.

Introduction

Ehlers-Danlos Syndrome encompasses a spectrum of genetically distinct connective tissue disorders with overlapping phenotypic features. While the primary clinical focus has traditionally been on joint and skin manifestations, there is growing interest in the systemic impacts of connective tissue abnormalities, including bone health. Anecdotal reports and observational studies have raised concerns about increased fracture risk in EDS patients, particularly in the hypermobile and classical subtypes. This review explores the evidence linking EDS to fractures and outlines potential pathophysiological mechanisms and clinical implications.

Pathophysiological Basis of Fracture Risk in EDS

Connective Tissue and Bone Integrity

EDS is associated with mutations affecting collagen or collagen-modifying enzymes, crucial for the structural integrity of skin, ligaments, and bone. Defective collagen can impair the organization and strength of the bone matrix, potentially compromising bone quality and increasing susceptibility to fractures (Brady et al., 2017).

Bone Mineral Density (BMD) Alterations

Several studies have reported decreased BMD in EDS subtypes:

• Brady et al. (2017) found reduced BMD in individuals with classical and vascular EDS, suggesting inherent bone fragility.
• Malfait et al. (2010) also documented bone involvement in various forms of EDS, though hypermobile EDS (hEDS) showed more variable BMD findings.

Factors such as chronic pain, reduced mobility, nutritional deficiencies (e.g., calcium or vitamin D), and glucocorticoid exposure may further contribute to compromised bone density in this population.

Clinical Evidence of Fracture Incidence

Adult Populations

Clinical reports suggest that adults with EDS may experience low-impact or atraumatic fractures, often attributed to joint instability or falls related to proprioceptive deficits (Grahame & Hakim, 2006). However, large-scale epidemiological studies quantifying fracture incidence in EDS remain limited.

Pediatric Considerations

Children with EDS appear to have an elevated risk of fractures, especially during early development. A retrospective study by Kisilevsky et al. (2011) reported multiple fractures in pediatric EDS patients, occasionally leading to misdiagnosis of non-accidental trauma (NAT). This has significant implications for forensic and child protection assessments.

Biomechanical Factors

• Joint Hypermobility and Falls: Individuals with joint hypermobility are prone to falls, joint dislocations, and altered gait, which can indirectly increase fracture risk (Castori et al., 2010).
• Muscle Weakness and Proprioception Deficits: Impaired proprioception and muscle tone in EDS can compromise balance and reaction time, contributing to injury during daily activities (Rombaut et al., 2012).

Differential Diagnoses and Overlap Syndromes

It is crucial to differentiate EDS from other connective tissue disorders associated with bone fragility, such as osteogenesis imperfecta (OI). In some cases, particularly where the genetic diagnosis is uncertain, features may overlap. Clinicians should also be aware of dual diagnoses and consider genetic testing when fracture patterns appear atypical or severe.

Clinical Recommendations

• Bone Health Monitoring: DEXA scans should be considered in EDS patients with low-impact fractures or other risk factors for osteoporosis.
• Fall Prevention: Physical therapy focused on proprioception, strength, and balance may reduce fall risk.
• Nutritional Support: Adequate intake of vitamin D and calcium should be ensured.
• Caution in Pediatrics: Awareness of EDS-associated fractures is critical to prevent misclassification as abuse.

Conclusion

Although fractures are not a defining feature of EDS, current evidence suggests an increased risk exists, particularly in children and adults with severe hypermobility, low BMD, or frequent falls. A multifactorial model including connective tissue fragility, biomechanical instability, and lifestyle factors likely contributes to this risk. Clinicians should maintain a high index of suspicion for bone health issues in EDS patients and employ proactive management strategies to minimize morbidity.

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Castori, M., Morlino, S., Pascolini, G., Blundo, C., & Grammatico, P. (2010). Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 154C(1), 96–101. https://doi.org/10.1002/ajmg.c.30261

Grahame, R., & Hakim, A. J. (2006). Joint hypermobility syndrome is a highly prevalent but poorly recognized musculoskeletal disorder. British Medical Journal, 332(7544), 639–640. https://doi.org/10.1136/bmj.332.7544.639

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Malfait, F., Wenstrup, R. J., & De Paepe, A. (2010). Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genetics in Medicine, 12(10), 597–605. https://doi.org/10.1097/GIM.0b013e3181eed412

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