Spinal fracture

Summary

Spinal fracture (MONDO:0005309) is a disease with 1 cohort gene (4 GWAS associations across 18 studies) and 51 clinical trials. Top therapeutic interventions include risedronic acid and teriparatide.

At a glance

• Cohort genes: 1
• GWAS associations: 4
• Clinical trials: 51

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinal fracture
Mondo ID	MONDO:0005309
EFO	EFO:0003902
MeSH	D016103
SNOMED CT	50448004
Anatomy (UBERON)	UBERON:0001130
Is cancer (heuristic)	no

Also known as: bone fracture of vertebral column · vertebral column bone fracture

Data availability: 4 GWAS associations (18 studies).

Disease family

Classification path: injury › bone fracture › spinal fracture

Related subtypes (6): humerus fracture, tibia fracture, ulna fracture, radius fracture, hip fracture, jaw fracture

Genetics & variants

GWAS landscape

4 GWAS associations across 18 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10190845	1e-09	FBLN7 - ZC3H8	A	1.75
rs2290492	3e-07	ST8SIA2	A	1.23
rs1493960	3e-07	MICAL2	?
rs7121756	4e-07	OR5BD1P - CYCSP26	A	1.22

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90479210	Verma A	2024	7,763	437,280	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90652055	Liu TY	2025	3,320	210,203	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90080970	Backman JD	2021	1,842	385,220	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084956	Backman JD	2021	1,842	385,220	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST005097	Alonso N	2017	1,553	4,340	Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.
GCST90436825	Zhou W	2018	1,352	387,765	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90044644	Jiang L	2021	1,258	455,090	A generalized linear mixed model association tool for biobank-scale data.
GCST90479209	Verma A	2024	973	120,063	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480974	Verma A	2024	973	120,063	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080967	Backman JD	2021	745	386,833	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	3

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	2
3_prime_UTR_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10190845	2	112192944	A>C,G	0.03	intergenic_variant	FBLN7 - ZC3H8	1e-09	Tier 4: intronic/intergenic
rs2290492	15	92464744	G>A,C,T	0.23	3_prime_UTR_variant	ST8SIA2	3e-07	Tier 2: splice/UTR
rs1493960	11	12322815	T>A,C	0.05	intron_variant	MICAL2	3e-07	Tier 4: intronic/intergenic
rs7121756	11	57980425	G>A	0.29	intergenic_variant	OR5BD1P - CYCSP26	4e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBLN7	Orphanet:684742	2q13 microdeletion syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FBLN7	HGNC:26740	ENSG00000144152	Q53RD9	Fibulin-7	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBLN7	Fibulin-7	An adhesion molecule that interacts with extracellular matrix molecules in developing teeth and may play important roles in differentiation and maintenance of odontoblasts as well as in dentin formation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBLN7	Complement	yes		EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, EGF

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBLN7	179	ubiquitous	yes	secondary oocyte, oocyte, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBLN7	898

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBLN7	Q53RD9	82.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell adhesion	1	37.5×	0.027	FBLN7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FBLN7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	FBLN7
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FBLN7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 51.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	44
PHASE3	4
PHASE4	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00749242	PHASE4	COMPLETED	Comparative Study of Balloon Kyphoplasty and Conservative Treatment
NCT02784782	PHASE4	UNKNOWN	Thoracolumbar Burstfractures, Orthesis or No Orthesis
NCT00068822	PHASE3	COMPLETED	Vertebroplasty for the Treatment of Fractures Due to Osteoporosis
NCT00343252	PHASE3	COMPLETED	Effect of Teriparatide Compared to Risedronate on Back Pain in Women With a Spine Fracture Caused by Osteoporosis
NCT01123512	PHASE3	COMPLETED	The Kiva® System as a Vertebral Augmentation Treatment
NCT04956588	PHASE3	COMPLETED	Evaluation of the Safety and Efficacy of Smart Orthopedic Minimally Invasive Surgical Systems for Spinal Surgery
NCT02566655	PHASE1	COMPLETED	Clinical Trial of Intravenous Infusion of Fucosylated Bone Marrow Mesenchyme Cells in Patients With Osteoporosis
NCT03253952	Not specified	ACTIVE_NOT_RECRUITING	A Study of Autonomic Dynamic Dysfunction to Predict Infections After Spinal Cord Injury.
NCT05170815	Not specified	RECRUITING	Clariance ErYs Registry
NCT05769114	Not specified	RECRUITING	Surgical Versus Non-Surgical Treatment of Thoracolumbar Burst Fracture
NCT06200298	Not specified	ACTIVE_NOT_RECRUITING	Effectiveness of Erector Spinae Plane Block for Percutaneous Arthrodesis of Spinal Fractures
NCT07147504	Not specified	NOT_YET_RECRUITING	Relationship Between Mortality Rates of Fractures in Different Sites and Several Factors in Elderly Patients
NCT00211237	Not specified	COMPLETED	CAFE Study - Cancer Patient Fracture Evaluation
NCT00290862	Not specified	UNKNOWN	A Safety and Efficacy Study for Treatment of Painful Vertebral Compression Fractures Caused by Osteoporosis
NCT00594321	Not specified	WITHDRAWN	Evaluation of Fracture Fixation With Energy and Cement in Tumors of the Spine
NCT00994032	Not specified	COMPLETED	Quality of Life After Vertebroplasty Versus Conservative Treatment in Patients With Painful Osteoporotic Vertebral Fractures
NCT01761084	Not specified	COMPLETED	Build Better Bones With Exercise
NCT02179697	Not specified	WITHDRAWN	Randomized Trial With an Observational Component of Non-operative Versus Operative Treatment for AO Type A3 Fractures
NCT02234414	Not specified	COMPLETED	Epidemiology, Identification Rate and Treatment Penetration of Osteoporotic Vertebral Fractures in Switzerland
NCT02252185	Not specified	COMPLETED	A Clinical Study of a Spine Fusion System in Vertebral Body Fusion Surgery
NCT02432495	Not specified	COMPLETED	Anterior Screw Fixation Versus Halo Immobilization of Type II Odontoid Fractures in Geriatric Patients With Increased Anesthesia Risk
NCT02461810	Not specified	COMPLETED	Prospective Comparative Study to Compare Safety and Effectiveness of Two Vertebral Compression Fracture Reduction Techniques
NCT02603874	Not specified	UNKNOWN	The Development of a Vertebra Localizing Aid Medical Device
NCT02657265	Not specified	COMPLETED	SpineJack® Versus Conservative Treatment Study (SPICO Study)
NCT02719340	Not specified	COMPLETED	Short Segment Fixation in Thoracolumbar Osteoporotic Fracture
NCT02768675	Not specified	UNKNOWN	Intra-operative Assessment of the Intellirod LOADPRO Spinal Rod Strain Sensor for Use During Kyphotic Corrective Surgery
NCT02789774	Not specified	UNKNOWN	Uppsala Study on Odontoid Fracture Treatment in the Elderly
NCT02826889	Not specified	COMPLETED	Assessing the Diagnostic Accuracy of Corrected Flow Time (FTc) and Pleth Variability Index (PVI) as Predictors of Fluid Responsiveness in Patients in the Prone Position Using the Jackson Table
NCT02839057	Not specified	COMPLETED	Survival After Surgical Treatment of Axis Fractures in Elderly
NCT02840695	Not specified	COMPLETED	Effect of Biological Disease Modifying Anti Rheumatic Drug (bDMARD) Treatment on Spinal Fracture Incidence in Patients With Ankylosing Spondylitis (AS)
NCT02918669	Not specified	COMPLETED	Study to Investigate the Long Term Survivorship of Coflex
NCT02931266	Not specified	TERMINATED	PASS MIS® Post-market Clinical Follow-up
NCT02931279	Not specified	COMPLETED	PASS OCT® Post-market Clinical Follow-up
NCT02950532	Not specified	COMPLETED	Posterior Ligament Complex Assessment Without Magnetic Resonance Image in Thoracolumbar Fractures
NCT03269851	Not specified	COMPLETED	Parameters of Neurological Deficit After Thoracolumbar Fractures
NCT03272243	Not specified	COMPLETED	Short Segment vs Long Segment Fixation in Traumatic Dorsolumbar Spine Fractures
NCT03312998	Not specified	UNKNOWN	Incidence of Metal Failure During First Year Following Transpedicular Screws Fixation of Dorsolumbar Spine Fracture
NCT03316703	Not specified	UNKNOWN	Surgical Treatment of the Thoracolumbar Spine Fractures.
NCT03359941	Not specified	TERMINATED	Acupuncture Treatment for Vertebral Compression Fracture
NCT03360383	Not specified	UNKNOWN	Effect and Essentiality of Vertebroplasty Surgery in Acute Vertebral Compression Fractures

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RISEDRONIC ACID	4	1
TERIPARATIDE	4	1