Increased Bone Resorption during Lactation in Pycnodysostosis

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telo...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-02, Vol.22 (4), p.1810
Main Authors: Jansen, Ineke D C, Papapoulos, Socrates E, Bravenboer, Nathalie, de Vries, Teun J, Appelman-Dijkstra, Natasha M
Format: Article
Language:English
Subjects:
Adult
bone remodeling
Bone Resorption - enzymology
Bone Resorption - genetics
Bone Resorption - pathology
cathepsin K
Cathepsin K - deficiency
Cathepsin K - metabolism
Cathepsin L - genetics
Cathepsin L - metabolism
Cathepsins - genetics
Cathepsins - metabolism
Female
Humans
lactation
Lactation - metabolism
osteoclasts
Osteoclasts - enzymology
Osteoclasts - pathology
osteocytes
Pycnodysostosis - enzymology
Pycnodysostosis - genetics
Pycnodysostosis - pathology
pycnodystostosis
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Summary:Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22041810