Frozen shoulder
diseaseOn this page
Also known as adhesive capsulitisadhesive capsulitis of shoulder
Summary
Frozen shoulder (MONDO:0006763) is a disease with 5 GWAS associations across 4 studies and 265 clinical trials. Top therapeutic interventions include lidocaine, amitriptyline, and collagenase clostridium histolyticum. A subtype of arthropathy — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 5
- Clinical trials: 265
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | frozen shoulder |
| Mondo ID | MONDO:0006763 |
| EFO | EFO:1000941 |
| DOID | DOID:14188 |
| ICD-10-CM | M75.0 |
| SNOMED CT | 399114005 |
| UMLS | C0311223 |
| MedGen | 90227 |
| MedDRA | 10017391 |
| Is cancer (heuristic) | no |
Also known as: adhesive capsulitis · adhesive capsulitis of shoulder
Data availability: 5 GWAS associations (4 studies).
Disease family
This is a subtype of arthropathy. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › arthropathy › frozen shoulder
Related subtypes (23): transient arthropathy, synovial plica syndrome, hypermobility syndrome, Tietze syndrome, neurogenic arthropathy, Behcet syndrome arthropathy, ankylosis, bursitis, synovium neoplasm, hydrarthrosis, articular cartilage disorder, hemarthrosis, tenosynovitis, ganglion or cyst of synovium/tendon/bursa, spondyloarthropathy, temporomandibular joint disorder, arthritic joint disease, de Quervain disease, patellofemoral pain syndrome, secondary hypertrophic osteoarthropathy, shoulder impingement syndrome, crystal arthropathy, vertebral joint disorder
Genetics & variants
GWAS landscape
5 GWAS associations across 4 studies. Top hits map to 5 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs28971325 | 8e-37 | WNT7B | A | 1.21 |
| rs1042704 | 1e-12 | MMP14 | A | 1.12 |
| rs5777216 | 3e-10 | LINC01765 - NGF-AS1 | GT | 1.09 |
| rs17570529 | 3e-09 | AKAP13 | T | 0.92 |
| rs2472660 | 2e-08 | SFRP4, EPDR1 | C | 0.93 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90080532 | Backman JD | 2021 | 1,966 | 385,964 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90084518 | Backman JD | 2021 | 1,966 | 385,964 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90000512 | Green HD | 2021 | 0 | 0 | A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor. |
| GCST90000513 | Green HD | 2021 | 0 | 0 | A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 1 |
| Tier 4: intronic/intergenic | 3 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 5 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 3 |
| missense_variant | 1 |
| regulatory_region_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs28971325 | 22 | 45971264 | G>A | 0.233 | intron_variant | WNT7B | 8e-37 | Tier 4: intronic/intergenic |
| rs1042704 | 14 | 22843385 | G>A,C | 0.215 | missense_variant | MMP14 | 1e-12 | Tier 1: coding |
| rs5777216 | 1 | 115138945 | GT>G,GTT | 0.403 | regulatory_region_variant | LINC01765 - NGF-AS1 | 3e-10 | Tier 3: regulatory |
| rs17570529 | 15 | 85582376 | A>C,T | 0.266 | intron_variant | AKAP13 | 3e-09 | Tier 4: intronic/intergenic |
| rs2472660 | 7 | 37942359 | T>A,C | 0.355 | intron_variant | SFRP4, EPDR1 | 2e-08 | Tier 4: intronic/intergenic |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated for this disease
11 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Capsaicin | Approved (phase 4) |
| Cortisone Acetate | Approved (phase 4) |
| Dexamethasone | Approved (phase 4) |
| Lidocaine | Approved (phase 4) |
| Menthol | Approved (phase 4) |
| Methyl Salicylate | Approved (phase 4) |
| Methylprednisolone | Approved (phase 4) |
| Methylprednisolone Acetate | Approved (phase 4) |
| Prednisolone | Approved (phase 4) |
| Prednisone | Approved (phase 4) |
| Triamcinolone Acetonide | Approved (phase 4) |
| Hyaluronidase | Phase 3 (in late-stage trials) |
| Sodium Chloride | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adalimumab, Amitriptyline, Collagenase Clostridium Histolyticum.
Clinical trials & evidence
Clinical trials
Clinical trials: 265.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 233 |
| PHASE4 | 14 |
| PHASE2 | 10 |
| PHASE3 | 3 |
| PHASE1/PHASE2 | 2 |
| PHASE2/PHASE3 | 1 |
| EARLY_PHASE1 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02283996 | PHASE4 | RECRUITING | Adhesive Capsulitis: Prospective Analysis of Efficacy and Financial Impact for Use of Physical Therapy in Treatment |
| NCT07278323 | PHASE4 | NOT_YET_RECRUITING | Frozen Shoulder and Hormone Replacement Therapy |
| NCT07416916 | PHASE4 | RECRUITING | Ultrasound-Guided Intra-Articular vs Gluteal Intramuscular Corticosteroid Injection for Frozen Shoulder |
| NCT07497737 | PHASE4 | NOT_YET_RECRUITING | OMT for Adhesive Capsulitis |
| NCT00875862 | PHASE4 | TERMINATED | Shoulder Adhesive Capsulitis and Ambulatory Continuous Interscalene Nerve Blocks |
| NCT01087229 | PHASE4 | COMPLETED | Effectiveness of an Oxygen-nitrous Oxide Mixture During Physical Therapy for Frozen Shoulder |
| NCT02001740 | PHASE4 | COMPLETED | An RCT in Treatment of Adhesive Capsulitis Arthrographic Joint Distention With Local Anesthetic Alone |
| NCT02944526 | PHASE4 | COMPLETED | The Effect of 3 Ropivacaine Suprascapular Nerve Blocks in Subacute Adhesive Capsulitis: a Randomized Controlled Trial |
| NCT03479502 | PHASE4 | COMPLETED | Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis |
| NCT04931511 | PHASE4 | TERMINATED | Comparison Between Subacromial Ultrasound Guided and Systemic Steroid Injection for Frozen Shoulder |
| NCT04965376 | PHASE4 | UNKNOWN | A Trial Comparing Glenohumeral Joint Steroid Injection Versus Suprascapular Nerve Block in Patients With Frozen Shoulder |
| NCT05131269 | PHASE4 | COMPLETED | Prolotherapy Intervention in Patient With Frozen Shoulder |
| NCT05844930 | PHASE4 | COMPLETED | A Study to Determine the Safety and Effectiveness of a Connective Tissue Allograft (ActiveMatrix) Verses Standard of Care in Adhesive Capsulitis of the Shoulder |
| NCT05977985 | PHASE4 | UNKNOWN | The Effects of Rotator Interval Hydro-dissection in Primary Adhesive Capsulitis. |
| NCT07057037 | PHASE3 | ACTIVE_NOT_RECRUITING | Phase 3 Study of the Efficacy and Safety of MR Arthrography Using the NEMO-103 Injection in Patients With Known or Suspected Shoulder Joint Diseases |
| NCT01570985 | PHASE3 | UNKNOWN | Treatment Study of Frozen Shoulder: Corticosteroid Injection in Joint Versus Wait and See Policy |
| NCT04347733 | PHASE3 | COMPLETED | Hyaluronidase in Intra-articular Steroid Injection Treating the Adhesive Capsulitis for Shoulder |
| NCT05299242 | PHASE2/PHASE3 | COMPLETED | The Anti-Freaze-F Study- Anti-TNF for Treatment of Frozen Shoulder - a Feasibility Study |
| NCT06976671 | PHASE2 | RECRUITING | A Study to Determine the Safety and Efficacy of Bevacizumab Administered Via Injection Into the Shoulder Joint of Participants With Adhesive Capsulitis (Frozen Shoulder) |
| NCT00261196 | PHASE2 | WITHDRAWN | Collagenase in the Treatment of Adhesive Capsulitis (Frozen Shoulder) |
| NCT01157221 | PHASE1/PHASE2 | COMPLETED | Prediction Frozen Shoulder Validation |
| NCT01306708 | PHASE2 | COMPLETED | Amitriptyline Regarding Nimesulide in Acute Idiopathic Adhesive Capsulitis |
| NCT01483963 | PHASE2 | COMPLETED | AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder |
| NCT01526031 | PHASE2 | COMPLETED | Bee Venom Acupuncture for the Treatment of Frozen Shoulder |
| NCT02006719 | PHASE2 | COMPLETED | Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder |
| NCT02206542 | PHASE2 | UNKNOWN | Scientifically Merged Acupuncture and Robot-assisted Technology (SMART) for Rehabilitation of Frozen Shoulder Syndrome: Second-year Project-Comparison of Robot and Conventional Physiotherapy (Including Preliminary Test on Healthy Volunteers) |
| NCT03676829 | PHASE1/PHASE2 | UNKNOWN | Embolization for the Treatment of Pain Secondary to Adhesive Capsulitis |
| NCT04160091 | PHASE2 | TERMINATED | Study to Evaluate the Efficacy and Safety of FX006 in Patients With Glenohumeral Osteoarthritis or Shoulder Adhesive Capsulitis |
| NCT04496167 | PHASE2 | COMPLETED | Safety and Efficacy of EN3835 in Participants With Frozen Shoulder |
| NCT06626568 | PHASE2 | COMPLETED | Comparison of Ultrasound-Guided Subacromial vs. Systemic Steroid Injections for Frozen Shoulder: a Multicenter Pilot Study |
| NCT04831255 | PHASE1 | TERMINATED | ZILRETTA™ for Treatment of Idiopathic Adhesive Capsulitis |
| NCT03951896 | EARLY_PHASE1 | COMPLETED | Efficacy of Platelet Rich Plasma Injections in Patients With Adhesive Capsulitis of the Shoulder |
| NCT05214547 | Not specified | RECRUITING | Effectiveness of Focal Vibration in Shoulder Pathology |
| NCT05384093 | Not specified | RECRUITING | Outcomes of Treatment Using the ERMI Shoulder Flexionater ® |
| NCT06041282 | Not specified | RECRUITING | Conservative Treatment of Early Adhesive Capsulitis |
| NCT06129006 | Not specified | NOT_YET_RECRUITING | Ultrasound Guided Shoulder Anterior Capsular Infiltration Plus Hydrodilatation With Steroid Versus Hyalase in Patients With Frozen Shoulder |
| NCT06176248 | Not specified | RECRUITING | Evaluation of the Efficacy of Suprascapular Nerve Block in Adhesive Capsulitis |
| NCT06201468 | Not specified | ENROLLING_BY_INVITATION | Frozen Shoulder (Scapular Mobilization Versus Scapular PNF) |
| NCT06229964 | Not specified | RECRUITING | Frozen Shoulder Treatment with Intra-Articular Corticosteroid Injection and Suprascapular Nerve Block |
| NCT06377644 | Not specified | ACTIVE_NOT_RECRUITING | Comparing the Efficacy of KT vs DN With Conventional Treatment for Improving QOL and Alleviating Pain in Frozen Shoulder |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| LIDOCAINE | 4 | 8 |
| AMITRIPTYLINE | 4 | 3 |
| COLLAGENASE CLOSTRIDIUM HISTOLYTICUM | 4 | 3 |
| DOXYCYCLINE ANHYDROUS | 4 | 3 |
| TRIAMCINOLONE ACETONIDE | 4 | 2 |
| DEXTROSE | 4 | 1 |
| FLUPHENAZINE DECANOATE | 4 | 1 |
| GUANFACINE HYDROCHLORIDE | 4 | 1 |
| HYALURONIDASE | 4 | 1 |
| METHYLPREDNISOLONE | 4 | 1 |
| TRIAMCINOLONE HEXACETONIDE | 4 | 1 |
| OZONE | 3 | 1 |
| CHEMBL423707 | 0 | 1 |