Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2022 Oct 27

PMID 36292765

Authors

Nipith Charoenngam

Aryan Nasr

Arash Shirvani

Michael F Holick

Affiliations

Soon will be listed here.

Abstract

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

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References

Chodirker B, Coburn S, Seargeant L, Whyte M, Greenberg C . Increased plasma pyridoxal-5'-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia. J Inherit Metab Dis. 1990; 13(6):891-6. DOI: 10.1007/BF01800216. View

Winn N, Lalam R, Cassar-Pullicino V . Imaging of Paget's disease of bone. Wien Med Wochenschr. 2016; 167(1-2):9-17. DOI: 10.1007/s10354-016-0517-3. View

Choy M . Pharmaceutical Approval Update. P T. 2018; 43(6):326-327. PMC: 5969208. View

Steward C . Neurological aspects of osteopetrosis. Neuropathol Appl Neurobiol. 2003; 29(2):87-97. DOI: 10.1046/j.1365-2990.2003.00474.x. View

Polyzos S, Anastasilakis A, Litsas I, Efstathiadou Z, Kita M, Arsos G . Profound hypocalcemia following effective response to zoledronic acid treatment in a patient with juvenile Paget's disease. J Bone Miner Metab. 2010; 28(6):706-12. DOI: 10.1007/s00774-010-0198-8. View

Tosi L, Oetgen M, Floor M, Huber M, Kennelly A, McCarter R . Initial report of the osteogenesis imperfecta adult natural history initiative. Orphanet J Rare Dis. 2015; 10:146. PMC: 4650321. DOI: 10.1186/s13023-015-0362-2. View

Tavormina P, Shiang R, Thompson L, Zhu Y, Wilkin D, Lachman R . Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet. 1995; 9(3):321-8. DOI: 10.1038/ng0395-321. View

Vajo Z, Francomano C, Wilkin D . The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocr Rev. 2000; 21(1):23-39. DOI: 10.1210/edrv.21.1.0387. View

Imel E, Glorieux F, Whyte M, Munns C, Ward L, Nilsson O . Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019; 393(10189):2416-2427. PMC: 7179969. DOI: 10.1016/S0140-6736(19)30654-3. View

10.

Pacifici M . Hereditary multiple exostoses: are there new plausible treatment strategies?. Expert Opin Orphan Drugs. 2019; 6(6):385-391. PMC: 6707746. DOI: 10.1080/21678707.2018.1483232. View

11.

Akhurst R . Targeting TGF-β Signaling for Therapeutic Gain. Cold Spring Harb Perspect Biol. 2017; 9(10). PMC: 5630004. DOI: 10.1101/cshperspect.a022301. View

12.

Baroncelli G, Toschi B, Bertelloni S . Hypophosphatemic rickets. Curr Opin Endocrinol Diabetes Obes. 2012; 19(6):460-7. DOI: 10.1097/MED.0b013e328358be97. View

13.

Deng Q, Li P, Che M, Liu J, Biswas S, Ma G . Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin. Elife. 2019; 8. PMC: 6764825. DOI: 10.7554/eLife.50208. View

14.

Fratzl-Zelman N, Valenta A, Roschger P, Nader A, Gelb B, Fratzl P . Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab. 2004; 89(4):1538-47. DOI: 10.1210/jc.2003-031055. View

15.

Nassar K, Rachidi W, Janani S, Mkinsi O . Van Buchem's Disease. Joint Bone Spine. 2016; 83(6):737-738. DOI: 10.1016/j.jbspin.2015.10.013. View

16.

Pacifici M . The pathogenic roles of heparan sulfate deficiency in hereditary multiple exostoses. Matrix Biol. 2017; 71-72:28-39. PMC: 6015767. DOI: 10.1016/j.matbio.2017.12.011. View

17.

Petje G, Meizer R, Radler C, Aigner N, Grill F . Deformity correction in children with hereditary hypophosphatemic rickets. Clin Orthop Relat Res. 2008; 466(12):3078-85. PMC: 2628230. DOI: 10.1007/s11999-008-0547-2. View

18.

CHANG T, Wang Y, Liu A, Tung J . Thanatophoric dysplasia type I. Acta Paediatr Taiwan. 2001; 42(1):39-41. View

19.

Kose O, Ertas A, Celiktas M, Kisin B . Fracture of an osteochondroma treated successfully with total excision: two case reports. Cases J. 2009; 2:8062. PMC: 2769397. DOI: 10.4076/1757-1626-2-8062. View

20.

Linglart A, Biosse-Duplan M, Briot K, Chaussain C, Esterle L, Guillaume-Czitrom S . Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014; 3(1):R13-30. PMC: 3959730. DOI: 10.1530/EC-13-0103. View