Osteoporosis

Summary

Osteoporosis (MONDO:0005298) is a disease (an umbrella term covering 7 Mondo subtypes) caused by WNT11 (GenCC Strong), with 23 cohort genes (175 GWAS associations across 75 studies) and 1,303 clinical trials. The dominant Reactome pathway is GP1b-IX-V activation signalling (3 cohort genes). Top therapeutic interventions include alendronic acid, zoledronic acid anhydrous, and risedronic acid.

At a glance

• Causal gene: WNT11 (GenCC Strong)
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 23
• GWAS associations: 175
• ClinVar variants: 299
• Clinical trials: 1,303

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteoporosis
Mondo ID	MONDO:0005298
EFO	EFO:0003882
MeSH	D010024
OMIM	166710
DOID	DOID:11476
ICD-10-CM	M81
ICD-11	2113001430
NCIT	C3298
SNOMED CT	64859006
UMLS	C0029456
MedGen	14535
Is cancer (heuristic)	no

Also known as: bone mineral density quantitative trait locus · osteoporosis, involutional · osteoporosis, postmenopausal

Data availability: 299 ClinVar variants · 175 GWAS associations (75 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › bone resorption disease › osteoporosis

Related subtypes (2): osteitis fibrosa, lytic metastatic bone lesion

Subtypes (7): nephrolithiasis/osteoporosis, hypophosphatemic, postmenopausal osteoporosis, X-linked osteoporosis with fractures, idiopathic juvenile osteoporosis, drug-induced osteoporosis, pregnancy associated osteoporosis, premenopausal osteoporosis

Genetics & variants

GWAS landscape

175 GWAS associations across 75 studies. Top hits map to 11 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr7:121326736	2e-40		G	0.15
chr11:68450822	1e-27		T	0.11
chr7:38103230	4e-27		A	0.11
chr13:42378009	1e-23		T	0.09
chr1:22379941	2e-23		T	0.13
rs9533090	6e-23	LINC02341	C	0.1
chr6:152008780	3e-21		C	0.1
rs4869741	3e-20	CCDC170	T	0.1
chr17:43721253	4e-20		A	0.16
rs4870044	5e-20	CCDC170	C	0.1
chr1:22681214	6e-20		C	0.13
chr2:118752917	3e-19		GC	0.5
chr3:41082493	5e-19		A	0.08
rs9533095	1e-18	LINC02341	G	0.09
chr6:151687789	1e-18		T	0.08
rs56364616	3e-18	FAM3C	C	0.1
rs2062375	7e-18	TNFRSF11B - RNU6-12P	G	0.09
rs917726	1e-17	FAM3C	A	0.1
chr7:96488606	1e-17		C	0.08
rs9272364	3e-17	HLA-DQA1	G	0.11
rs6679981	3e-17	PPIAP34 - ZBTB40	G	0.11
chr7:96135274	6e-17		A	0.09
rs142005327	1e-16	WNT16	GCT	0.16
chr8:120010833	2e-16		G	0.09
chr6:127125645	2e-16		C	0.08
chr21:38969070	3e-16		ACAGCCACC	0.09
rs9594738	4e-16	LINC02341	T	0.14
rs34434863	5e-16	HLA-DRB1 - HLA-DQA1	T	0.1
chr1:68172467	9e-16		T	0.09
rs4988321	3e-15	LRP5	G	0.17

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474135	UK Biobank Whole-Genome Sequencing Consortium	2025	25,063	433,377	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90476259	Verma A	2024	20,117	422,420	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90297613	Auwerx C	2024	12,274	291,530	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297667	Auwerx C	2024	12,274	291,530	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297714	Auwerx C	2024	12,274	291,530	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297761	Auwerx C	2024	12,274	291,530	Rare copy-number variants as modulators of common disease susceptibility.
GCST90080559	Backman JD	2021	10,456	373,627	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084545	Backman JD	2021	10,456	373,627	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018667	Sakaue S	2021	9,794	168,932	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018887	Sakaue S	2021	8,520	479,981	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	32
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	18

Functional consequences

Consequence	Count
unknown	26
intron_variant	12
intergenic_variant	10
missense_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr7:121326736							2e-40	Tier 4: intronic/intergenic
chr11:68450822							1e-27	Tier 4: intronic/intergenic
chr7:38103230							4e-27	Tier 4: intronic/intergenic
chr13:42378009							1e-23	Tier 4: intronic/intergenic
chr1:22379941							2e-23	Tier 4: intronic/intergenic
rs9533090	13	42377313	C>G,T	0.471	intron_variant	LINC02341	6e-23	Tier 4: intronic/intergenic
chr6:152008780				0.419			3e-21	Tier 4: intronic/intergenic
rs4869741	6	151585158	T>A,C,G	0.384	intron_variant	CCDC170	3e-20	Tier 4: intronic/intergenic
chr17:43721253							4e-20	Tier 4: intronic/intergenic
rs4870044	6	151580274	C>T	0.383	intron_variant	CCDC170	5e-20	Tier 4: intronic/intergenic
chr1:22681214				0.201			6e-20	Tier 4: intronic/intergenic
chr2:118752917							3e-19	Tier 4: intronic/intergenic
chr3:41082493							5e-19	Tier 4: intronic/intergenic
rs9533095	13	42394913	G>T	0.421	intron_variant	LINC02341	1e-18	Tier 4: intronic/intergenic
chr6:151687789							1e-18	Tier 4: intronic/intergenic
rs56364616	7	121377420	C>A	0.301	intron_variant	FAM3C	3e-18	Tier 4: intronic/intergenic
rs2062375	8	118965553	G>A,C	0.394	intergenic_variant	TNFRSF11B - RNU6-12P	7e-18	Tier 4: intronic/intergenic
rs917726	7	121378803	A>T	0.299	intron_variant	FAM3C	1e-17	Tier 4: intronic/intergenic
chr7:96488606							1e-17	Tier 4: intronic/intergenic
rs9272364	6	32636822	G>A	0.291	intergenic_variant	HLA-DQA1	3e-17	Tier 4: intronic/intergenic
rs6679981	1	22371367	G>A	0.199	intergenic_variant	PPIAP34 - ZBTB40	3e-17	Tier 4: intronic/intergenic
chr7:96135274				0.35			6e-17	Tier 4: intronic/intergenic
rs142005327	7	121329916	GCT>G,GCTCT	0.259	intron_variant	WNT16	1e-16	Tier 4: intronic/intergenic
chr8:120010833				0.44			2e-16	Tier 4: intronic/intergenic
chr6:127125645							2e-16	Tier 4: intronic/intergenic
chr21:38969070							3e-16	Tier 4: intronic/intergenic
rs9594738	13	42378009	C>T	0.489	intron_variant	LINC02341	4e-16	Tier 4: intronic/intergenic
rs34434863	6	32591896	T>A,C,G	0.288	intergenic_variant	HLA-DRB1 - HLA-DQA1	5e-16	Tier 4: intronic/intergenic
chr1:68172467							9e-16	Tier 4: intronic/intergenic
rs4988321	11	68406721	G>A,C	0.053	missense_variant	LRP5	3e-15	Tier 1: coding

ClinVar germline variants

299 retrieved; paginated sample, class counts are floors:

107 uncertain significance, 68 likely benign, 35 benign/likely benign, 30 conflicting classifications of pathogenicity, 24 pathogenic, 19 pathogenic/likely pathogenic, 12 likely pathogenic, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076006	NM_000088.4(COL1A1):c.288del (p.Asp97fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1254747	NM_000088.4(COL1A1):c.1177C>T (p.Gln393Ter)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342741	NM_000088.4(COL1A1):c.1444G>A (p.Gly482Arg)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1431093	NM_000088.4(COL1A1):c.1667del (p.Pro556fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17313	NM_000088.4(COL1A1):c.3541G>A (p.Gly1181Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17343	NM_000088.4(COL1A1):c.934C>T (p.Arg312Cys)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805989	NM_000088.4(COL1A1):c.3540del (p.Gly1181fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2772795	NM_000088.4(COL1A1):c.2597del (p.Gly866fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2780397	NM_000088.4(COL1A1):c.598G>A (p.Gly200Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
287320	NM_000088.4(COL1A1):c.2089C>T (p.Arg697Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3382929	NM_000088.4(COL1A1):c.635G>A (p.Gly212Glu)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35907	NM_000088.4(COL1A1):c.2062C>T (p.Gln688Ter)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35920	NM_000088.4(COL1A1):c.3076C>T (p.Arg1026Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425583	NM_000088.4(COL1A1):c.2343+1G>A	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425597	NM_000088.4(COL1A1):c.1243C>T (p.Arg415Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425606	NM_000088.4(COL1A1):c.2155G>A (p.Gly719Ser)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425618	NM_000088.4(COL1A1):c.3226G>A (p.Gly1076Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425639	NM_000088.4(COL1A1):c.769G>A (p.Gly257Arg)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
456724	NM_000088.4(COL1A1):c.1012G>A (p.Gly338Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
456782	NM_000088.4(COL1A1):c.3893C>A (p.Thr1298Asn)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
478914	NM_000088.4(COL1A1):c.3495del (p.Gly1166fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
4796574	NM_000088.4(COL1A1):c.2729del (p.Arg910fs)	COL1A1	Pathogenic	criteria provided, single submitter
499457	NM_000088.4(COL1A1):c.3065G>C (p.Gly1022Ala)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
546096	NM_000088.4(COL1A1):c.2299G>A (p.Gly767Ser)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
647159	NM_000088.4(COL1A1):c.1273G>A (p.Gly425Ser)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
870103	NM_000088.4(COL1A1):c.1646del (p.Pro549fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1694467	NM_000089.4(COL1A2):c.1531G>A (p.Gly511Ser)	COL1A2	Pathogenic	criteria provided, single submitter
265387	NM_000089.4(COL1A2):c.577G>A (p.Gly193Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2682437	NM_000089.4(COL1A2):c.739G>A (p.Gly247Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3594954	NM_000089.4(COL1A2):c.1523G>T (p.Gly508Val)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 58 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
WNT11	Strong	Autosomal dominant	osteoporosis	2
CALCR	No Known Disease Relationship	Unknown	osteoporosis

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis
MED12	Orphanet:1415	Hardikar syndrome
MED12	Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type
MED12	Orphanet:776	Lujan-Fryns syndrome
MED12	Orphanet:777	X-linked non-syndromic intellectual disability
MED12	Orphanet:93932	FG syndrome type 1
COL1A1	Orphanet:1310	Caffey disease
COL1A1	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A1	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A1	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A1	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A1	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A1	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A1	Orphanet:287	Classical Ehlers-Danlos syndrome
COL1A1	Orphanet:31112	Dermatofibrosarcoma protuberans
COL1A1	Orphanet:314029	High bone mass osteogenesis imperfecta
COL1A2	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A2	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A2	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A2	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A2	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A2	Orphanet:230851	Cardiac-valvular Ehlers-Danlos syndrome
COL1A2	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A2	Orphanet:314029	High bone mass osteogenesis imperfecta
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa
MECOM	Orphanet:402020	Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
MECOM	Orphanet:71289	Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
LRP5	Orphanet:178377	Osteosclerosis-developmental delay-craniosynostosis syndrome
LRP5	Orphanet:2783	Autosomal dominant osteopetrosis type 1
LRP5	Orphanet:2788	Osteoporosis-pseudoglioma syndrome
LRP5	Orphanet:2790	Endosteal hyperostosis, Worth type
LRP5	Orphanet:2924	Isolated polycystic liver disease
LRP5	Orphanet:3416	Hyperostosis corticalis generalisata
LRP5	Orphanet:498481	LRP5-related primary osteoporosis

Cohort genes → proteins

23 cohort genes, 22 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	12
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CALCR	HGNC:1440	ENSG00000004948	P30988	Calcitonin receptor	gencc,clinvar
WNT11	HGNC:12776	ENSG00000085741	O96014	Protein Wnt-11	gencc
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
SCG2	HGNC:10575	ENSG00000171951	P13521	Secretogranin-2	gwas
BTF3P11	HGNC:1126	ENSG00000118903		basic transcription factor 3 pseudogene 11	gwas
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	clinvar
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
OSBPL1A	HGNC:16398	ENSG00000141447	Q9BXW6	Oxysterol-binding protein-related protein 1	gwas
SOX6	HGNC:16421	ENSG00000110693	P35712	Transcription factor SOX-6	gwas
TBC1D8	HGNC:17791	ENSG00000204634	O95759	TBC1 domain family member 8	gwas
SGPP2	HGNC:19953	ENSG00000163082	Q8IWX5	Sphingosine-1-phosphate phosphatase 2	gwas
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	clinvar
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	clinvar
DOK6	HGNC:28301	ENSG00000206052	Q6PKX4	Docking protein 6	gwas
LRRC4C	HGNC:29317	ENSG00000148948	Q9HCJ2	Leucine-rich repeat-containing protein 4C	gwas
MECOM	HGNC:3498	ENSG00000085276	Q03112	Histone-lysine N-methyltransferase MECOM	gwas
FTCDNL1	HGNC:48661	ENSG00000226124	E5RQL4	Formiminotransferase N-terminal subdomain-containing protein	gwas
LRP5	HGNC:6697	ENSG00000162337	O75197	Low-density lipoprotein receptor-related protein 5	clinvar
OPA1	HGNC:8140	ENSG00000198836	O60313	Dynamin-like GTPase OPA1, mitochondrial	clinvar
ALDH7A1	HGNC:877	ENSG00000164904	P49419	Alpha-aminoadipic semialdehyde dehydrogenase	gwas
SERPINF1	HGNC:8824	ENSG00000132386	P36955	Pigment epithelium-derived factor	clinvar
RAP1A	HGNC:9855	ENSG00000116473	P62834	Ras-related protein Rap-1A	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CALCR	Calcitonin receptor	G protein-coupled receptor activated by ligand peptides amylin (IAPP), calcitonin (CT/CALCA) and calcitonin gene-related peptide type 1 (CGRP1/CALCA).
WNT11	Protein Wnt-11	Ligand for members of the frizzled family of seven transmembrane receptors.
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
SCG2	Secretogranin-2	Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules.
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
OSBPL1A	Oxysterol-binding protein-related protein 1	Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate.
SOX6	Transcription factor SOX-6	Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation.
TBC1D8	TBC1 domain family member 8	May act as a GTPase-activating protein for Rab family protein(s).
SGPP2	Sphingosine-1-phosphate phosphatase 2	Has specific phosphohydrolase activity towards sphingoid base 1-phosphates.
COL1A1	Collagen alpha-1(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
COL1A2	Collagen alpha-2(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
DOK6	Docking protein 6	DOK proteins are enzymatically inert adaptor or scaffolding proteins.
LRRC4C	Leucine-rich repeat-containing protein 4C	May promote neurite outgrowth of developing thalamic neurons.
MECOM	Histone-lysine N-methyltransferase MECOM	Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.
LRP5	Low-density lipoprotein receptor-related protein 5	Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.
OPA1	Dynamin-like GTPase OPA1, mitochondrial	Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function.
ALDH7A1	Alpha-aminoadipic semialdehyde dehydrogenase	Aldehyde dehydrogenase enzyme that mediates important protective effects.
SERPINF1	Pigment epithelium-derived factor	Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells.
RAP1A	Ras-related protein Rap-1A	Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner.

Protein-family classification

Druggable: 6 · Difficult: 4 · Unknown: 13 · Druggable fraction: 0.26

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
Ion channel	1	4.8×	0.715
Scaffold/PPI	2	1.5×	0.715
Antibody/Immunoglobulin	1	1.3×	0.715
Kinase	1	1.2×	0.715
Enzyme (other)	2	1.0×	0.715
GPCR	1	1.0×	0.715
Other/Unknown	13	1.0×	0.715
Transcription factor	2	0.7×	0.786

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CALCR	GPCR	yes		GPCR_2_secretin-like, GPCR_2_calcitonin_rcpt, GPCR_2_extracellular_dom
WNT11	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
SCG2	Other/Unknown	no		Granin, Chromogranin_CS, ScgII
BTF3P11	Other/Unknown	no
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
OSBPL1A	Scaffold/PPI	no		Oxysterol-bd, PH_domain, Ankyrin_rpt
SOX6	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
TBC1D8	Other/Unknown	no		Rab-GAP-TBC_dom, GRAM, EF-hand-dom_pair
SGPP2	Other/Unknown	no		PAP2/HPO, PAP2/HPO_sf
COL1A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily
OFD1	Other/Unknown	no		LisH, OFD1
DOK6	Scaffold/PPI	no		PH_domain, IRS_PTB, PH-like_dom_sf
LRRC4C	Antibody/Immunoglobulin	yes		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
MECOM	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
FTCDNL1	Other/Unknown	no		Formiminotransferase_N, FormiminoTrfase_cat_dom_sf, Formiminotransferase_N_sf
LRP5	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
OPA1	Enzyme (other)	yes	3.6.5.5	Dynamin_GTPase, Dynamin, P-loop_NTPase
ALDH7A1	Enzyme (other)	yes	1.2.1.3	Aldehyde_DH_dom, Ald_DH/histidinol_DH, Ald_DH_N
SERPINF1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
RAP1A	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

21 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	23
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endometrium epithelium	2
tibia	2
gastrocnemius	2
left ovary	2
bronchial epithelial cell	2
periodontal ligament	2
skin of hip	2
stromal cell of endometrium	2
right lobe of liver	2
hair follicle	1
adipose tissue of abdominal region	1
omental fat pad	1
peritoneum	1
gluteal muscle	1
hindlimb stylopod muscle	1
islet of Langerhans	1
lateral nuclear group of thalamus	1
type B pancreatic cell	1
Brodmann (1909) area 10	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CALCR	71	tissue_specific	marker	tibia, endometrium epithelium, hair follicle
WNT11	178	broad	marker	omental fat pad, peritoneum, adipose tissue of abdominal region
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
SCG2	216	broad	marker	type B pancreatic cell, islet of Langerhans, lateral nuclear group of thalamus
BTF3P11	76		yes	male germ line stem cell (sensu Vertebrata) in testis, endometrium epithelium, Brodmann (1909) area 10
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
OSBPL1A	283	ubiquitous	marker	corpus callosum, medial globus pallidus, globus pallidus
SOX6	235	ubiquitous	marker	epithelial cell of pancreas, tibia, kidney epithelium
TBC1D8	283	ubiquitous	marker	mucosa of stomach, bronchial epithelial cell, epithelium of bronchus
SGPP2	226	broad	marker	ileal mucosa, upper arm skin, upper leg skin
COL1A1	298	ubiquitous	marker	stromal cell of endometrium, skin of hip, periodontal ligament
COL1A2	295	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium
DOK6	198	broad	marker	cortical plate, substantia nigra pars compacta, substantia nigra pars reticulata
LRRC4C	206	broad	marker	middle temporal gyrus, buccal mucosa cell, Brodmann (1909) area 23
MECOM	276	ubiquitous	marker	cardia of stomach, renal medulla, pylorus
FTCDNL1	165	ubiquitous	yes	gastrocnemius, muscle of leg, primordial germ cell in gonad
LRP5	224	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, ascending aorta
OPA1	288	ubiquitous	marker	adrenal tissue, calcaneal tendon, endothelial cell
ALDH7A1	255	ubiquitous	marker	right lobe of liver, ventricular zone, left ovary
SERPINF1	280	ubiquitous	marker	pigmented layer of retina, pericardium, endocervix
RAP1A	295	ubiquitous	marker	blood vessel layer, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRC	11,608
COL1A1	5,341
ALDH7A1	4,544
MED12	3,322
OFD1	2,878
OPA1	2,630
LRP5	2,619
MECOM	2,442
RYR1	2,177
SOX6	2,151

Intra-cohort edges

A	B	Sources
COL1A1	COL1A2	intact
LRP5	LRRC4C	biogrid_interaction, intact
LRP5	WNT11	string_interaction
MECOM	SOX6	biogrid_interaction

Structural data

PDB: 13 · AlphaFold-only: 9 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRC	P12931	79
CALCR	P30988	32
ALDH7A1	P49419	20
COL1A1	P02452	14
OPA1	O60313	11
OSBPL1A	Q9BXW6	6
COL1A2	P08123	5
RAP1A	P62834	4
MED12	Q93074	3
SERPINF1	P36955	3
RYR1	P21817	2
LRRC4C	Q9HCJ2	1
MECOM	Q03112	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT11	O96014	90.35
SGPP2	Q8IWX5	83.19
TBC1D8	O95759	79.20
LRP5	O75197	78.65
FTCDNL1	E5RQL4	76.93
DOK6	Q6PKX4	74.63
OFD1	O75665	68.41
SCG2	P13521	58.07
SOX6	P35712	56.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 215. Enrichment computed across 23 evidence-associated genes (18 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
GP1b-IX-V activation signalling	3	158.6×	2e-04	SRC, COL1A1, COL1A2
Defective VWF binding to collagen type I	2	423.0×	5e-04	COL1A1, COL1A2
Enhanced cleavage of VWF variant by ADAMTS13	2	317.2×	5e-04	COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant	2	317.2×	5e-04	COL1A1, COL1A2
Platelet Aggregation (Plug Formation)	3	73.2×	5e-04	SRC, COL1A1, COL1A2
MET activates PTK2 signaling	3	63.4×	5e-04	SRC, COL1A1, COL1A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	181.3×	0.001	COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V	2	181.3×	0.001	COL1A1, COL1A2
Anchoring fibril formation	2	84.6×	0.005	COL1A1, COL1A2
p130Cas linkage to MAPK signaling for integrins	2	84.6×	0.005	SRC, RAP1A
GRB2:SOS provides linkage to MAPK signaling for Integrins	2	79.3×	0.005	SRC, RAP1A
Platelet Adhesion to exposed collagen	2	74.6×	0.006	COL1A1, COL1A2
Scavenging by Class A Receptors	2	66.8×	0.006	COL1A1, COL1A2
Fibronectin matrix formation	2	63.4×	0.006	COL1A1, COL1A2
Crosslinking of collagen fibrils	2	63.4×	0.006	COL1A1, COL1A2
RUNX2 regulates osteoblast differentiation	2	50.8×	0.009	SRC, COL1A1
Syndecan interactions	2	47.0×	0.010	COL1A1, COL1A2
Integrin signaling	2	47.0×	0.010	SRC, RAP1A
Signaling by high-kinase activity BRAF mutants	2	35.2×	0.016	SRC, RAP1A
GPVI-mediated activation cascade	2	34.3×	0.016	COL1A1, COL1A2
MAP2K and MAPK activation	2	31.7×	0.018	SRC, RAP1A
Signaling by RAF1 mutants	2	30.9×	0.018	SRC, RAP1A
RET signaling	2	28.8×	0.018	SRC, DOK6
Collagen chain trimerization	2	28.8×	0.018	COL1A1, COL1A2
Signaling by moderate kinase activity BRAF mutants	2	28.2×	0.018	SRC, RAP1A
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	28.2×	0.018	SRC, RAP1A
Signaling downstream of RAS mutants	2	28.2×	0.018	SRC, RAP1A
Developmental Lineage of Pancreatic Ductal Cells	2	25.4×	0.021	COL1A1, COL1A2
Assembly of collagen fibrils and other multimeric structures	2	22.3×	0.026	COL1A1, COL1A2
Class B/2 (Secretin family receptors)	2	21.1×	0.028	CALCR, WNT11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skin morphogenesis	2	133.8×	0.012	COL1A1, COL1A2
branching involved in mammary gland duct morphogenesis	2	133.8×	0.012	SRC, LRP5
cellular response to retinoic acid	3	33.4×	0.012	WNT11, COL1A1, SERPINF1
L-lysine catabolic process	1	802.5×	0.032	ALDH7A1
protein heterotrimerization	1	802.5×	0.032	COL1A2
cellular response to vitamin E	1	802.5×	0.032	COL1A1
negative regulation of endosome to plasma membrane protein transport	1	802.5×	0.032	ALDH7A1
mitochondrial inner membrane fusion	1	802.5×	0.032	OPA1
regulation of caveolin-mediated endocytosis	1	802.5×	0.032	SRC
obsolete glycine betaine biosynthetic process from choline	1	401.2×	0.032	ALDH7A1
spinal cord oligodendrocyte cell differentiation	1	401.2×	0.032	SOX6
regulation of toll-like receptor 3 signaling pathway	1	401.2×	0.032	SRC
positive regulation of dephosphorylation	1	401.2×	0.032	SRC
cloacal septation	1	401.2×	0.032	WNT11
response to antineoplastic agent	1	401.2×	0.032	RAP1A
calcitonin family receptor signaling pathway	1	401.2×	0.032	CALCR
cellular response to fluoride	1	401.2×	0.032	COL1A1
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	401.2×	0.032	OFD1
odontogenesis	2	50.1×	0.032	SRC, COL1A2
Wnt signaling pathway, planar cell polarity pathway	2	43.4×	0.032	MED12, WNT11
negative regulation of extrinsic apoptotic signaling pathway	2	40.1×	0.032	SCG2, SRC
embryonic skeletal system development	2	37.3×	0.032	WNT11, COL1A1
blood vessel development	2	35.7×	0.032	COL1A1, COL1A2
outflow tract morphogenesis	2	29.2×	0.032	RYR1, WNT11
cellular response to amino acid stimulus	2	29.2×	0.032	COL1A1, COL1A2
cell fate commitment	2	28.2×	0.032	WNT11, SOX6
positive regulation of ERK1 and ERK2 cascade	3	12.2×	0.032	CALCR, SRC, RAP1A
positive regulation of DNA-templated transcription	5	6.7×	0.032	MED12, WNT11, COL1A1, MECOM, LRP5
cellular response to transforming growth factor beta stimulus	2	26.3×	0.032	SOX6, COL1A1
bone mineralization	2	25.9×	0.032	WNT11, COL1A2

Therapeutics

Drugs indicated or in trials for this disease

11 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Abaloparatide	Approved (phase 4)
Calcium Carbonate	Approved (phase 4)
Cholecalciferol	Approved (phase 4)
Cyanocobalamin	Approved (phase 4)
Denosumab	Approved (phase 4)
Estradiol	Approved (phase 4)
Estrogens, Conjugated	Approved (phase 4)
Folic Acid	Approved (phase 4)
Pyridoxine	Approved (phase 4)
Romosozumab	Approved (phase 4)
Teriparatide	Approved (phase 4)

33 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Alendronic Acid	Phase 3
Alfacalcidol	Phase 3
Bazedoxifene	Phase 3
Calcitonin Salmon	Phase 3
Calcitriol	Phase 3
Calcium	Phase 3
Calcium Gluconate	Phase 3
Eldecalcitol	Phase 3
Ergocalciferol	Phase 3
Gonadorelin	Phase 3
Hesperidin	Phase 3
Ibandronic Acid	Phase 3
Lasofoxifene	Phase 3
Letrozole	Phase 3
Medroxyprogesterone Acetate	Phase 3
Menatetrenone	Phase 3
Minodronic Acid	Phase 3
Nitroglycerin	Phase 3
Odanacatib	Phase 3
Parathyroid Hormone	Phase 3
Phytonadione	Phase 3
Progesterone	Phase 3
Raloxifene	Phase 3
Risedronic Acid	Phase 3
SMC021	Phase 3
Tibolone	Phase 3
Arzoxifene	Phase 2
Ethinyl Estradiol	Phase 2
Ginger	Phase 2
Lactobacillus Acidophilus	Phase 2
Norgestimate	Phase 2
Strontium	Phase 2
Teriparatide Acetate	Phase 2

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 19

Druggability breadth: 12 of 23 evidence-associated genes (52%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CALCR	PRAMLINTIDE
SRC	PONATINIB
OPA1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRC	103	4
CALCR	3	4
OPA1	2	4
MED12	1	2
WNT11	0	0
RYR1	0	0
SCG2	0	0
BTF3P11	0	0
OSBPL1A	0	0
SOX6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PRAMLINTIDE	4	CALCR
CALCITONIN SALMON	4	CALCR
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
SUNITINIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC
CRIZOTINIB	4	SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SRC	1,917	Binding:1858, Functional:43, ADMET:16
CALCR	34	Binding:24, Functional:10
RYR1	16	Binding:13, Functional:3
COL1A1	8	Binding:8
MED12	6	Binding:6
RAP1A	6	Binding:6
COL1A2	4	Functional:4
OPA1	2	Binding:2
MECOM	1	Binding:1
LRP5	1	Binding:1
ALDH7A1	1	Binding:1
SERPINF1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRC	2.7.10.2	non-specific protein-tyrosine kinase
OPA1	3.6.5.5	dynamin GTPase
ALDH7A1	1.2.1.3, 1.2.1.31	aldehyde dehydrogenase (NAD+), L-aminoadipate-semialdehyde dehydrogenase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SRC	1,917

Pharmacogenomics

Cohort genes with a PharmGKB record: 23; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1

Chemical tractability of cohort targets

29 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.

Compound	Max phase	Cohort target (bioactivity)
PRAMLINTIDE	4	CALCR
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
SUNITINIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC
CRIZOTINIB	4	SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CALCR, SRC, OPA1
B	Phased (≥1) drug, not yet approved	1	MED12
C	Druggable family + PDB, no drug	3	RYR1, LRRC4C, ALDH7A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	16	WNT11, SCG2, BTF3P11, OSBPL1A, SOX6, TBC1D8, SGPP2, COL1A1, COL1A2, OFD1 (+6 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WNT11	0	—
RYR1	16	—
SCG2	0	—
BTF3P11	0	—
OSBPL1A	0	—
SOX6	0	—
TBC1D8	0	—
SGPP2	0	—
COL1A1	8	—
COL1A2	4	—
OFD1	0	—
DOK6	0	—
LRRC4C	0	—
MECOM	1	—
FTCDNL1	0	—
LRP5	1	—
ALDH7A1	1	—
SERPINF1	1	—
RAP1A	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,303.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	568
PHASE3	159
PHASE4	150
PHASE2	112
PHASE1	87
PHASE1/PHASE2	12
PHASE2/PHASE3	7
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03623633	PHASE4	ACTIVE_NOT_RECRUITING	Comparative Antiresorptive Efficacy Discontinuation of Denosumab
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT04467983	PHASE4	ACTIVE_NOT_RECRUITING	Abaloparatide Added to Ongoing Denosumab vs Continued Denosumab Alone
NCT05058976	PHASE4	ACTIVE_NOT_RECRUITING	Romosozumab Use to Build Skeletal Integrity
NCT05091086	PHASE4	ACTIVE_NOT_RECRUITING	The Optimal Long Term Treatment Strategy of Anti-resorptive Medications
NCT05101018	PHASE4	ACTIVE_NOT_RECRUITING	Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI
NCT05493761	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease
NCT05655013	PHASE4	ACTIVE_NOT_RECRUITING	Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis 2 (ZOLARMAB2)
NCT05666310	PHASE4	ACTIVE_NOT_RECRUITING	Muscle Impact of Treating Osteoporosis
NCT06059222	PHASE4	RECRUITING	The Optimised Use of Romozosumab Study
NCT06118905	PHASE4	RECRUITING	Preserving Geriatric Muscle With an Osteoporosis Medication
NCT06264609	PHASE4	ENROLLING_BY_INVITATION	Precision Medicine Approach for Osteoporosis - Follow Up Study
NCT06332014	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Efficacy and Safety of Prolia in Subjects of Male Osteoporosis in Mainland China
NCT06439758	PHASE4	NOT_YET_RECRUITING	Effects of First-Line Oral Hypoglycemics in Bone Markers of Treatment Naïve Saudi Adults With Type 2 Diabetes
NCT06558188	PHASE4	RECRUITING	Combined Anabolic Therapy
NCT06938152	PHASE4	RECRUITING	Effects of Cycle Therapy vs Sequential Therapy With Romosozumab and Denosumab in Postmenopausal Osteoporosis Patients
NCT07154719	PHASE4	RECRUITING	GLP-1R Actions on Muscle and the Skeleton
NCT07165158	PHASE4	NOT_YET_RECRUITING	The Effect of Semaglutide on Bone Health
NCT07271771	PHASE4	RECRUITING	The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity
NCT07281586	PHASE4	RECRUITING	Step-down Therapy After Long-term Osteoporosis Treatment
NCT07283887	PHASE4	RECRUITING	Romosozumab and Denosumab, Alone or Combined, in Postmenopausal Osteoporosis
NCT07406685	PHASE4	NOT_YET_RECRUITING	The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation
NCT00006180	PHASE4	COMPLETED	Bone Loss in Premenopausal Women With Depression
NCT00035256	PHASE4	COMPLETED	Sequential Use of Teriparatide and Raloxifene HCl in the Treatment of Postmenopausal Women With Osteoporosis
NCT00035971	PHASE4	COMPLETED	EVA: Evista Alendronate Comparison
NCT00114556	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
NCT00130403	PHASE4	COMPLETED	OPTAMISE: Clinical Effectiveness of Teriparatide After Alendronate or Risedronate Therapy in Osteoporotic Postmenopausal Women
NCT00148915	PHASE4	COMPLETED	A Study To Assess the Quality and Strength of Bone in Women Participants With Osteoporosis Taking Oral Ibandronate Versus Placebo
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT00165607	PHASE4	COMPLETED	Randomized, Open, Parallel, Active Controlled Study on Fracture Prevention in Antiosteoporosis Treatment (OF Study)
NCT00168909	PHASE4	COMPLETED	Influence of Alfacalcidol on Falls in Osteopenic/Osteoporotic Postmenopausal Women (ALFA Study)
NCT00182871	PHASE4	COMPLETED	Testosterone Effects on Bone and Frailty
NCT00191425	PHASE4	COMPLETED	2-Year Therapy With Teriparatide vs 1-yr Therapy Followed by 1-Year of Raloxifene or Calcium/Vit D in Severe Postmenopausal Osteoporosis
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00221299	PHASE4	COMPLETED	Risedronate and Parathyroid Hormone to Reverse Osteoporosis Caused by Chronic Steroid Use
NCT00252408	PHASE4	COMPLETED	Danish Osteoporosis Prevention Study
NCT00259298	PHASE4	COMPLETED	Evaluation of the Effects of Teriparatide on Skeleton Images in Postmenopausal Women With Osteoporosis
NCT00261625	PHASE4	COMPLETED	Can Alendronate Suppress Calcification and Improve Bone Density in Chronic Peritoneal Dialysis Patients?
NCT00271713	PHASE4	COMPLETED	Impact of Oral Ibandronate 150 mg Monthly on Structural Properties of Bone in Postmenopausal Osteoporosis (SPIMOS-3D)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALENDRONIC ACID	4	174
ZOLEDRONIC ACID ANHYDROUS	4	95
RISEDRONIC ACID	4	79
TERIPARATIDE	4	49
DENOSUMAB	4	39
RALOXIFENE	4	36
CALCIUM	4	30
CALCIUM CARBONATE	4	15
IBANDRONIC ACID	4	14
ERGOCALCIFEROL	4	13
ROMOSOZUMAB	4	13
PARATHYROID HORMONE	4	12
BAZEDOXIFENE	4	11
CHOLECALCIFEROL	4	8
ABALOPARATIDE	4	7
ALFACALCIDOL	4	6
ESTRADIOL	4	4
ESTROGENS, CONJUGATED	4	4
MINODRONIC ACID	4	4
PAMIDRONIC ACID	4	4
POTASSIUM CITRATE ANHYDROUS	4	4
CALCITRIOL	4	3
CALCIUM GLUCONATE	4	3
LASOFOXIFENE	4	3
LETROZOLE	4	3
SOMATROPIN	4	3
VITAMIN K	4	3
ATORVASTATIN	4	2
CALCITONIN	4	2
CALCITONIN SALMON	4	2