Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia

Nicola Hepp; Anja Lisbeth Frederiksen; Morten Dunø; Niklas Rye Jørgensen; Bente Lomholt Langdahl; Poul Vedtofte; Hanne B. Hove; Klaus Hindsø; Jens-Erik Beck Jensen

doi:10.1007/s00223-019-00605-1

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia

Nicola Hepp^*, Anja Lisbeth Frederiksen, Morten Dunø, Niklas Rye Jørgensen, Bente Lomholt Langdahl, Poul Vedtofte, Hanne B. Hove, Klaus Hindsø, Jens-Erik Beck Jensen

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

Abstract

Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

Originalsprog	Engelsk
Tidsskrift	Calcified Tissue International
Vol/bind	105
Sider (fra-til)	681-686
Antal sider	6
ISSN	0171-967X
DOI	https://doi.org/10.1007/s00223-019-00605-1
Status	Udgivet - 2019

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10.1007/s00223-019-00605-1

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title = "Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia",

abstract = "Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.",

keywords = "Bone healing, CTSK, Fracture, Hypophosphatasia, Pycnodysostosis",

author = "Nicola Hepp and Frederiksen, {Anja Lisbeth} and Morten Dun{\o} and J{\o}rgensen, {Niklas Rye} and Langdahl, {Bente Lomholt} and Poul Vedtofte and Hove, {Hanne B.} and Klaus Hinds{\o} and Jensen, {Jens-Erik Beck}",

year = "2019",

doi = "10.1007/s00223-019-00605-1",

language = "English",

volume = "105",

pages = "681--686",

journal = "Calcified Tissue International",

issn = "0171-967X",

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TY - JOUR

T1 - Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia

AU - Hepp, Nicola

AU - Frederiksen, Anja Lisbeth

AU - Dunø, Morten

AU - Jørgensen, Niklas Rye

AU - Langdahl, Bente Lomholt

AU - Vedtofte, Poul

AU - Hove, Hanne B.

AU - Hindsø, Klaus

AU - Jensen, Jens-Erik Beck

PY - 2019

Y1 - 2019

N2 - Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

AB - Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

KW - Bone healing

KW - CTSK

KW - Fracture

KW - Hypophosphatasia

KW - Pycnodysostosis

U2 - 10.1007/s00223-019-00605-1

DO - 10.1007/s00223-019-00605-1

M3 - Journal article

C2 - 31489468

AN - SCOPUS:85072025101

SN - 0171-967X

VL - 105

SP - 681

EP - 686

JO - Calcified Tissue International

JF - Calcified Tissue International

ER -

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia

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