Details of Disease

General Information of Disease (ID: DISO7RI8)

• Disease Name: Metabolic bone disease
• Disease Class: FB8Y: Osteopathy/chondropathy
• Definition: A group of disorders that affect the bones secondary to increased levels of minerals or deficient levels of minerals such as calcium, magnesium, phosphorus, and vitamin D. Representative examples are osteomalacia, osteoporosis, and Paget disease.
• Disease Hierarchy:
  DISE1F82: Bone disease
  DISO7RI8: Metabolic bone disease
• ICD Code:
  ICD-11: ICD-11: FB8Y
  Expand ICD-11: 'FB8Y
• Disease Identifiers:
  MONDO ID: MONDO_0800486
  MESH ID: D001851
  UMLS CUI: C0005944
  MedGen ID: 2699
  SNOMED CT ID: 50279003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
BPS-804	DMDYZRS	Phase 2	Antibody	[1]
Strontium malonate	DML814V	Phase 2	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GLB1	TTNGJPH	Limited	Genetic Variation	[3]
SOST	TTYRO4F	moderate	Biomarker	[4]
ALPL	TTMR5UV	Strong	Genetic Variation	[5]
DKK1	TTE3RAC	Strong	Biomarker	[6]
ESR1	TTZAYWL	Strong	Biomarker	[7]
HCAR2	TTWNV8U	Strong	Genetic Variation	[8]
IGF1R	TTQFBMY	Strong	Therapeutic	[9]
KCNMA1	TTE87WJ	Strong	Biomarker	[10]
LRP2	TTPH1AJ	Strong	Biomarker	[11]
MMP2	TTLM12X	Strong	Biomarker	[12]
IGF1	TTT6LOU	Definitive	Therapeutic	[9]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Biomarker	[13]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP27A1	DEBS639	Strong	Biomarker	[14]
CYP2R1	DEBIHM3	Strong	Biomarker	[14]
DHCR7	DEL7GFA	Strong	Biomarker	[14]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PHEX	OTG7N3J7	Limited	Altered Expression	[15]
ADCY10	OTYSTB0R	Strong	Genetic Variation	[8]
ANKRD11	OTV0V70M	Strong	Biomarker	[16]
CTC1	OTRJY7QD	Strong	Biomarker	[17]
GC	OTWS63BY	Strong	Biomarker	[14]
KDM4B	OT5P1UPY	Strong	Biomarker	[18]
MAGEC3	OT0KDWZN	Strong	Genetic Variation	[8]
PCK2	OTJ8LX4N	Strong	Biomarker	[19]
PHOSPHO1	OT43A0JA	Strong	Biomarker	[13]
SAMD4A	OT4MKCC8	Strong	Biomarker	[20]
SLIT3	OTU8MKEU	Strong	Biomarker	[21]
TRAF4	OTJLRVMC	Strong	Biomarker	[22]

References

• [1] ClinicalTrials.gov (NCT01806610) Study of Safety and Tolerability of BPS804 in Patients With Late-stage Chronic Kidney Disease. U.S. National Institutes of Health.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022828)
• [3] Morquio B patient/caregiver survey: First insight into the natural course of a rare GLB1 related condition.Mol Genet Metab Rep. 2018 Jul 20;16:57-63. doi: 10.1016/j.ymgmr.2018.06.006. eCollection 2018 Sep.
• [4] Pharmacometrics and systems pharmacology for metabolic bone diseases.Br J Clin Pharmacol. 2019 Jun;85(6):1136-1146. doi: 10.1111/bcp.13881. Epub 2019 Feb 28.
• [5] A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia.Sci Rep. 2019 Jan 30;9(1):973. doi: 10.1038/s41598-018-37801-2.
• [6] The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling?.Semin Arthritis Rheum. 2011 Oct;41(2):170-7. doi: 10.1016/j.semarthrit.2011.01.006. Epub 2011 Mar 24.
• [7] Impact on bone of an estrogen receptor-alpha gene loss of function mutation.J Clin Endocrinol Metab. 2008 Aug;93(8):3088-96. doi: 10.1210/jc.2007-2397. Epub 2008 May 27.
• [8] Small-molecule suppression of misfolding of mutated human carbonic anhydrase II linked to marble brain disease.Biochemistry. 2009 Jun 16;48(23):5358-64. doi: 10.1021/bi900128e.
• [9] Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation.Int J Mol Med. 2011 Sep;28(3):455-62. doi: 10.3892/ijmm.2011.697. Epub 2011 May 11.
• [10] Osteopenia due to enhanced cathepsin K release by BK channel ablation in osteoclasts.PLoS One. 2011;6(6):e21168. doi: 10.1371/journal.pone.0021168. Epub 2011 Jun 14.
• [11] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.Cell. 1999 Feb 19;96(4):507-15. doi: 10.1016/s0092-8674(00)80655-8.
• [12] Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development.Dev Dyn. 2007 Jun;236(6):1683-93. doi: 10.1002/dvdy.21159.
• [13] Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in Phospho1(-/-) and Phospho1/Pi t1 Double-Knockout Mice.J Bone Miner Res. 2016 Jun;31(6):1275-86. doi: 10.1002/jbmr.2790. Epub 2016 May 17.
• [14] Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis.Arch Toxicol. 2014 Apr;88(4):997-1006. doi: 10.1007/s00204-013-1191-5. Epub 2014 Jan 1.
• [15] Cloning of human PEX cDNA. Expression, subcellular localization, and endopeptidase activity.J Biol Chem. 1998 May 29;273(22):13729-37. doi: 10.1074/jbc.273.22.13729.
• [16] An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda. Physiol Genomics. 2008 Feb 19;32(3):311-21. doi: 10.1152/physiolgenomics.00116.2007. Epub 2007 Nov 6.
• [17] Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet. 2012 Jan 22;44(3):338-42. doi: 10.1038/ng.1084.
• [18] Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs.Cell Stem Cell. 2012 Jul 6;11(1):50-61. doi: 10.1016/j.stem.2012.04.009.
• [19] Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1-Dependent Autophagy.Stem Cells. 2019 Dec;37(12):1542-1555. doi: 10.1002/stem.3091. Epub 2019 Oct 14.
• [20] RNA-binding protein SAMD4 regulates skeleton development through translational inhibition of Mig6 expression.Cell Discov. 2017 Jan 24;3:16050. doi: 10.1038/celldisc.2016.50. eCollection 2017.
• [21] Osteoclast-secreted SLIT3 coordinates bone resorption and formation.J Clin Invest. 2018 Apr 2;128(4):1429-1441. doi: 10.1172/JCI91086. Epub 2018 Mar 5.
• [22] TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2.Cell Death Differ. 2019 Dec;26(12):2652-2666. doi: 10.1038/s41418-019-0328-3. Epub 2019 May 10.