Skeletal Instability in hEDS

See below for Joint "Cracking" in hEDS

 See separate Information page for Assistive Devices

Skeletal instability is one of the defining features of hypermobile Ehlers-Danlos syndrome (hEDS). It involves joints that move too much or don’t stay in place, leading to dislocations, partial dislocations (subluxations), and ongoing pain or fatigue. This instability can affect nearly every joint in the body and often gets worse over time. While the clinical impact is familiar to patients and providers, research increasingly shows that joint instability in hEDS reflects complex abnormalities in connective tissue structure, cellular behavior, and neuromuscular control—not just hypermobility alone.

Prevalence

Skeletal instability is extremely common in people with hypermobile Ehlers-Danlos syndrome (hEDS), though exact numbers vary depending on how it is defined and studied.

• Generalized joint hypermobility is present in over 95% of individuals with hEDS.

• Clinical studies estimate that up to 80% of people with hEDS experience recurrent joint instability, including subluxations or dislocations.

• In pediatric clinics, instability is often noted in the knees (43.4%), spine (32.2%), and shoulders (31.2%).

• Adults frequently report instability in the same regions, as well as the hips, ankles, wrists, and jaw.

• Functional joint instability without complete dislocation is likely underreported, especially in children or those with limited access to specialty care.

• Females are disproportionately represented in hEDS cohorts (over 90% in some studies), and tend to report more severe and widespread joint instability.

Population-based prevalence data are limited due to diagnostic delays, underrecognition in males and non-White individuals, and the absence of a molecular test.

Symptoms

The symptoms of skeletal instability in hEDS range from mild discomfort to severe functional limitation. While symptom patterns vary by individual, some are nearly universal across the lifespan.

Common symptoms include

• Joints that feel loose, unstable, or like they may "give out"

• Frequent subluxations or dislocations, sometimes with minimal movement

• Sharp or aching joint pain, especially after use or with certain positions

• Chronic musculoskeletal pain that may radiate from unstable joints

• Fatigue, often due to muscle overuse and the energy cost of stabilizing lax joints

• Muscle spasms or tightness as the body tries to compensate

• Cracking or popping sounds during motion (crepitus)

• Swelling or inflammation after joint strain

• Difficulty with fine motor tasks (e.g., handwriting, gripping objects)

• Balance problems, clumsiness, or frequent falls, especially in children

• Activity avoidance due to fear of dislocation or pain flare

Symptoms often fluctuate daily and worsen with overuse, fatigue, illness, or hormonal shifts. Emotional distress, fear of movement, and post-traumatic stress responses are also common in those with repeated dislocations or long diagnostic journeys.

Why Joints Are Unstable in hEDS

People with hEDS have differences in their connective tissue, the material that supports and holds the body together. These differences affect joints, muscles, skin, and other structures. Instability in hEDS is often caused by

• Loose or overly flexible joints (joint hypermobility)

• Weak or stretchy connective tissue, especially collagen

• Poor proprioception (reduced joint awareness)

• Muscle weakness or low muscle tone

• Fragile skin that bruises easily or scars poorly

Because of these problems, joints don’t stay in place the way they should. This can cause the joints to move too much, wear down early, or be easily injured.

Estimates suggest that a significant percentage of people with hEDS—up to 80% in some clinical studies—experience joint instability in one or more areas. However, prevalence may vary depending on age, sex, activity level, and the presence of co-occurring symptoms.

What Causes It at a Deeper Level

In addition to tissue laxity, several biological mechanisms may underlie instability in hEDS:

• ECM disorganization: Collagen and fibronectin are often disorganized or fragmented in the skin and connective tissues of hEDS patients, reducing joint capsule strength.

• Fascial dysfunction: Abnormalities in fascial thickness, gliding, and myofibroblast activity may impair force transmission and joint control.

• Cellular dysregulation: Fibroblasts show increased migration, altered cytoskeletal structure, and upregulation of MMP-9, a protein that breaks down connective tissue.

• Impaired mechanotransduction: Cells may not respond appropriately to mechanical stress, weakening tissue adaptation and repair.

• Proprioceptive and motor control deficits: Reduced joint awareness and poor coordination increase injury risk and reinforce instability.

• Developmental and hormonal factors: Joint laxity tends to be highest in childhood and adolescence, particularly in females. Estrogen may contribute to connective tissue softness and may explain some of the observed sex differences.

Acute Management Considerations

• Reduction Techniques

  • Use slow, gentle, patient-guided reduction whenever possible.

  • Avoid high-force manipulations that could damage fragile connective tissues or precipitate further dislocations.

  • In cases of muscle spasm or severe pain, sedation may be cautiously employed, though this is often avoidable with gentle methods.

  • Consider forgoing reduction altogether if the joint self-resolves or is not functionally impaired, especially when reduction may worsen instability.

• Pain Control

  • First-line treatments include NSAIDs and acetaminophen. NSAIDs should be used cautiously in older adults or those with gastrointestinal sensitivity.

  • Opioids may be necessary in severe cases but should be used sparingly due to central sensitization, opioid-induced hyperalgesia, and risk of dependence.

  • Topical analgesics (e.g., lidocaine patches) and heat therapy may offer localized relief with fewer side effects.

  • Behavioral and cognitive pain strategies may be helpful, particularly for patients with recurrent dislocations and trauma-related responses.

• Imaging

  • Consider imaging (X-ray or MRI) in cases of new-onset joint dislocation, atypical presentation, suspected fracture, or neurologic involvement.

  • Dynamic imaging (e.g., flexion/extension radiographs) may be indicated for craniocervical or spinal instability.

  • Routine imaging is not always required for recurrent, previously evaluated joints.

• Bracing and Immobilization

  • Use braces or splints to provide short-term joint stabilization post-injury.

  • Limit immobilization duration to prevent muscle atrophy, proprioceptive decline, and further instability.

  • Frequent skin checks are essential to prevent pressure injuries due to fragile skin.

Longer-Term Considerations

• Recurrence Prevention

  • Most hEDS patients will experience recurrence; therefore, recurrence prevention should begin immediately after reduction.

  • Referral to physical and occupational therapy familiar with hEDS is essential.

  • Therapy should emphasize low-impact strengthening, neuromuscular retraining, proprioceptive enhancement, and joint protection strategies.

  • Protective bracing during high-risk activities may reduce recurrence without promoting long-term deconditioning.

• Multidisciplinary Care

  • Coordination with specialists including rheumatology, physical therapy, pain management, and psychology is often beneficial.

  • For recurrent dislocations, surgical evaluation may be warranted, though surgery in hEDS carries a higher complication rate and should be a last resort.

• Patient Education

  • Patients should be taught to recognize early signs of instability and adopt strategies for safe movement and activity pacing.

  • Bracing should be prescribed with clear guidance on when and how to use it.

  • Education on avoiding high-risk movements (e.g., extreme ROM, overhead lifting) is critical.

• Monitor for Complications

  • Watch for signs of neurological injury, autonomic flare (e.g., PoTS symptoms), or vascular compromise after dislocation—especially in the cervical spine or shoulder.

  • Be aware of the risk of craniocervical instability in patients with frequent neck subluxations.

  • Delayed healing and joint damage can result from repeated episodes, even in the absence of acute trauma.

Theoretical Considerations

• Proprioceptive Deficits as a Recurrence Driver

  • Empirical studies document proprioceptive impairment in hEDS; theoretically, targeted neuromotor rehabilitation may prevent further instability if started early.

• Impact of Hormonal and Systemic Factors

  • Estrogen-related joint laxity may contribute to recurrence risk in females; timing interventions around hormonal cycles might reduce dislocation frequency, though this remains unproven.

• Potential Role of Neuroplasticity-Based Rehabilitation

  • Early neuroplasticity-informed physical therapy (e.g., motor control retraining, visual-motor integration) may help correct maladaptive movement patterns that reinforce instability.

• Individualized Bracing Strategy

  • Providers may consider custom bracing or orthotic solutions adapted to specific joint mechanics or daily activities, although evidence is currently limited to clinical experience.

    
    

Treatment and Support

There is no cure for hEDS, but many people benefit from treatments that help stabilize their joints and reduce symptoms.

• Physical and Occupational Therapy

  • Strengthening exercises: Focused, low-impact exercises help build muscles to support joints better and reduce the risk of dislocations.

  • Proprioception training: Improves body awareness of joint position, balance, and coordination, which lowers the chance of falls or injuries.

  • Joint protection techniques: Teach safer ways to move, lift, and rest to reduce strain on unstable joints.

  • Activity pacing: Helps prevent overuse, fatigue, and flare-ups by balancing activity with rest.

  • Specialized guidance: Therapists who understand hEDS can adapt exercise programs, avoiding aggressive approaches that may worsen instability.

  • Occupational therapy: Provides strategies for daily activities, ergonomic adaptations, and tools that reduce strain in work, school, or home settings.

• Braces and Support Tools

  • Splints and braces: These provide short-term or activity-specific support for wrists, knees, fingers, or other unstable joints.

  • Orthotics or supportive shoes: These reduce pain in the feet, ankles, and knees by improving alignment and stability.

  • Mobility aids: Walkers, canes, or wheelchairs may be needed in severe cases to reduce falls, conserve energy, and improve independence.

  • Compression garments: These are stretchable clothing items such as sleeves, leggings, gloves, or custom jackets. Clinical studies show that they can improve balance, proprioception, and joint stability, and some patients also report pain reduction and better tolerance for daily activities. They are generally used alongside physiotherapy and rehabilitation rather than on their own.

  • Individualized approach: Supports should be chosen and fitted by professionals familiar with hEDS and regularly reassessed. This helps minimize complications such as muscle weakness from over-reliance on braces or skin injury from compression garments.

  • Adjunctive: Braces, orthotics, compression garments, and mobility aids should be viewed as temporary or activity-specific aids. They are most effective when combined with strengthening, proprioception training, and physical therapy, and should not replace active rehabilitation.

For more detailed guidance on when to use braces and support tools, why they may help, and how to choose among different options, see below for Braces, Orthotics, and Support Tools in hEDS: A Practical Guide.

Other Treatment Options

• Pain management

  • May include medications (e.g., NSAIDs, acetaminophen), physical treatments (heat, topical patches, TENS), or integrative therapies like acupuncture.

  • Multimodal approaches work best, and medications should be used cautiously to avoid side effects and long-term dependence.

  • For more detail, see Pain in hEDS.

• Prolotherapy

  • Definition: A type of injection therapy where an irritant solution (often dextrose, a sugar solution) is injected into tendons or around joints to try to stimulate healing and create scar tissue that strengthens ligaments.

  • Evidence in hEDS is very limited: the only mention comes from GeneReviews, which cites one study but provides no details on effectiveness or long-term outcomes. No randomized trials or large studies exist in hEDS.

  • Other research: Studies in other conditions (like knee arthritis or tendon injuries) show modest improvements in pain and function for some people, but results cannot be reliably applied to hEDS because connective tissue responds differently.

  • Risks and side effects: temporary pain, stiffness, or bruising after injections are common. Serious complications are rare but possible (nerve or blood vessel injury, infection). Fragile tissue in hEDS may increase these risks.

  • Guideline recommendations: No major guidelines currently recommend prolotherapy for hEDS. It is generally considered experimental. Insurance coverage is uncommon, and most patients must pay out-of-pocket.

  • Bottom line: Prolotherapy may be considered only when standard conservative options (like PT and bracing) have failed and surgery is not appropriate, but patients should know the evidence is weak and long-term benefits are unproven.

• Surgery

  • Surgery is often only used when there is significant damage or when all other options have failed.

  • Higher risks in hEDS: Fragile tissue and poor wound healing lead to slower recovery, infection, and joints becoming unstable again even after repair.

  • Repeat surgeries are common: Many patients need more than one operation, and results can be unpredictable.

  • Last resort: Surgery is considered only when conservative treatments (like physical therapy, bracing, or pain management) have failed and quality of life is severely affected.

  • For more detail, see Surgical Considerations in hEDS.

Additional Support

• Patient education: Learning how to manage activity levels and protect joints is essential. For more detail, see Pacing and Exercise.

• Mental health support: Dealing with chronic pain and disability can be emotionally exhausting. Therapy and support groups can help. For more detail, see Psychological Impacts.

When to Seek Specialized Care

Many people with hEDS benefit from working with a team of health professionals. Depending on symptoms and severity, this team might include

• A geneticist or rheumatologist to confirm diagnosis and oversee care

• Physical and occupational therapists to help with stability and daily function

• Pain specialists for long-term pain management

• Orthopedic doctors for evaluation of injuries or structural damage

• Neurologists for symptoms involving weakness, numbness, headaches, or instability in the spine or neck

• Mental health providers to support coping and well-being

In cases of craniocervical instability or other neurological complications, multidisciplinary evaluation and imaging may be needed. For pediatric patients, early referral to specialists can help address hypotonia (low muscle tone), delayed milestones, or joint injury before long-term disability develops.

Body Region Overview: Common Problems and Interventions

Diagnostic Tools

Skeletal instability in hEDS is diagnosed clinically. There is currently no molecular test to confirm the condition, so diagnosis relies on medical history, physical examination, and exclusion of other disorders.

Key diagnostic elements include

• Beighton score for generalized joint hypermobility

• Documentation of

  • Recurrent joint dislocations or subluxations without trauma

  • Objective evidence of joint instability at two or more sites

  • Systemic features (such as soft, stretchy skin, or a family history of hEDS)

• Exclusion of alternative diagnoses through targeted genetic testing and lab work

Imaging is often used to evaluate joint damage or structural issues

• X-rays and MRI can assess alignment, joint degeneration, or impingement.

• Dynamic imaging (e.g., flexion/extension studies) may be helpful in suspected craniocervical or spinal instability.

• Imaging in children is generally reserved for cases with clear dysfunction or suspected complications, due to the high rate of benign hypermobility in youth.

While connective tissue biopsies and plasma protein studies show promising differences in hEDS, they are not yet used in clinical practice. Diagnosis remains based on clinical judgment and pattern recognition.

Disparities and Diagnostic Barriers

Skeletal instability in hEDS is often underrecognized or misattributed, especially in populations that are already underdiagnosed with hEDS as a whole. These diagnostic barriers affect timely intervention, access to care, and long-term outcomes.

Several factors contribute to disparities

• Gender bias: hEDS is more commonly diagnosed in females, but skeletal instability is often overlooked in males, where joint symptoms may be attributed to sports injuries, behavioral issues, or other causes.

• Racial and ethnic bias: Most diagnostic tools, including the Beighton score, were developed in predominantly White populations. They may not reflect normal joint mobility variation in people of African, Asian, or Indigenous descent, leading to underdiagnosis in non-White groups.

• Socioeconomic barriers: Individuals with limited access to specialists, physical therapy, or genetic services may not receive a timely or accurate diagnosis. Skeletal instability may be dismissed as anxiety, deconditioning, or generalized pain.

• Pediatric misattribution: In children, joint instability may present as frequent falls, clumsiness, or reluctance to engage in physical activity. Without awareness of hEDS, these signs are often considered benign or behavioral.

• Provider knowledge gaps: Many healthcare providers are unfamiliar with the full range of musculoskeletal manifestations in hEDS. As a result, subluxations, joint pain, and instability may be treated as isolated problems rather than part of a connective tissue disorder.

Improving awareness, updating diagnostic criteria to reflect population diversity, and expanding provider education are critical steps toward reducing disparities in the recognition and management of skeletal instability in hEDS.

Prognosis

The prognosis of skeletal instability in hEDS varies widely. Some people experience manageable symptoms with supportive care, while others develop chronic pain, disability, or multisystem involvement.

• Children often present with hypotonia (low muscle tone), delayed motor milestones, and frequent joint injuries. Early intervention may reduce long-term complications.

• Adolescents and adults may develop persistent pain, fatigue, reduced activity tolerance, and progressive instability due to cumulative soft tissue damage.

• Recurrent injuries can lead to early degenerative joint changes, joint capsule laxity, and functional loss.

• While joint laxity may decrease with age, symptoms such as instability and pain often persist or worsen.

• With appropriate therapy, many individuals experience improvement in symptoms and quality of life—but rarely full resolution.

• Surgical outcomes are mixed and carry a high risk of complications in this population.

Ongoing, coordinated care can help slow functional decline, minimize complications, and support long-term adaptation.

Hormonal and Developmental Influences

Skeletal instability in hEDS often begins early and follows a trajectory influenced by age, sex, and hormonal factors.

• In childhood, joint laxity is typically most pronounced. Many children with hEDS show signs of hypotonia, delayed gross motor skills, and frequent falls or injuries.

• In adolescence, growth spurts and hormonal shifts may exacerbate instability. Female patients often report worsening symptoms around puberty.

• Estrogen affects connective tissue elasticity and may contribute to greater joint laxity and injury risk in females. Symptoms may fluctuate with hormonal cycles, pregnancy, or menopause.

• With aging, laxity often declines slightly, but this may be offset by accumulated joint damage, pain, and fatigue.

These developmental and hormonal factors should be considered when tailoring physical therapy, bracing, or pacing strategies—particularly in pediatric or adolescent patients.

Clinical Considerations for Medical Providers During and After Joint Subluxation or Dislocation in hEDS

Joint subluxations and dislocations in hypermobile Ehlers-Danlos syndrome (hEDS) require a distinct approach due to the condition’s unique pathophysiology. Providers must consider connective tissue fragility, altered pain processing, proprioceptive deficits, and a high recurrence risk. Management differs significantly from that of the general population, both acutely and in the long term.

Summary

Skeletal instability is a central part of life with hEDS. It is caused by a combination of connective tissue fragility, abnormal cellular behavior, proprioceptive deficits, and neuromuscular dysfunction. The result is joints that are prone to dislocation, injury, pain, and fatigue. These issues may begin in childhood and worsen over time, often affecting multiple body regions and interfering with daily life.

Fortunately, there are effective ways to reduce symptoms and improve joint function. Individualized physical therapy, knowledgeable emergency physicians, joint protection strategies, orthotic supports, and mental health care can significantly improve quality of life. In severe cases, bracing, assistive devices, or surgery may be needed. Working with knowledgeable healthcare providers and taking a proactive approach to joint care can help people with hEDS manage instability and maintain independence.

Joint "Cracking" in hEDS

What Causes Cracking in hEDS or Hypermobile People?

Joint Instability

• Loose or lax ligaments mean joints may move slightly out of alignment, leading to clicking, popping, or cracking as they shift back into place.

• These sounds can occur during both voluntary movements and everyday activities like walking or turning your head.

Subluxations

• A subluxation is when a joint partially slips out of place and then returns, often making an audible pop.

• This is more likely in hEDS due to poor connective tissue integrity.

Tendons Snapping Over Bony Prominences

• Because of altered joint mechanics, tendons may slip out of their normal track and snap back, making a loud or painful crack.

Gas Bubble Formation (Same as in Non-hypermobile People)

• The classic “cavitation” from synovial fluid still occurs, but may happen more easily or more frequently in hypermobile joints due to increased joint space and mobility.

Why Does Joint Cracking Happen More in hEDS?

Several interrelated factors contribute

• Joint Laxity and Instability

• The hallmark of hEDS is abnormal connective tissue, leading to loose ligaments and overly flexible joints.

• This allows joint surfaces to move beyond normal ranges, sometimes slipping partially out of place (subluxation) and returning, which can create audible pops or clicks.

• Frequent subluxations and micro-movements can cause repeated joint noises.

• Altered Joint Biomechanics

• The excessive range of motion and altered alignment of joint structures mean that bones and soft tissues may move in ways they weren’t designed to.

• This allows for recurrent escape and re-entry of joint surfaces, generating cracking or popping sounds.

• Soft Tissue and Fascial Abnormalities

• hEDS is also associated with differences in fascial and soft tissue composition, including reduced stiffness and altered interfascial gliding.

• These abnormalities may make tendons or fascia more likely to snap over bones or shift during motion, contributing to the noise.

• Gas Bubble Formation (Cavitation)

• As with all people, synovial joints can produce cracking sounds through gas bubble collapse when the joint is stretched or pressure changes occur.

• In hEDS, this may happen more often due to increased joint volume and mobility.

Is It Harmful?

• Often, joint cracking is benign, even in hEDS.

• However, in this population, it can be a sign of underlying joint instability, repeated stress, or microtrauma, especially if it’s accompanied by pain, swelling, or functional problems.

• The long-term consequences of frequent joint cracking in hEDS are not fully understood, but may include cumulative tissue strain or early joint degeneration in some individuals.

When to Be Concerned

• Cracking or popping is painful or occurs with sharp discomfort

• The joint locks, gives way, or feels unstable

• There is visible swelling or signs of inflammation

• It interferes with daily activities, sleep, or mobility

What Can Help?

• Joint stabilization exercises under the guidance of a knowledgeable physical therapist

• Muscle strengthening, especially of the deep stabilizers around joints

• Bracing or kinesiology taping for joints that frequently sublux or crack

• Avoiding hyperextension and repetitive loading

• Joint protection techniques and activity pacing

Summary

Joint cracking in hEDS is usually a reflection of increased mobility and reduced structural support, and while often harmless, it should not be ignored if accompanied by pain or instability. Early intervention with stabilization and protective strategies can help preserve joint function and reduce long-term strain.