Increased Bone Resorption during Lactation in Pycnodysostosis

International Journal of Molecular Sciences, vol. 22, pp. 1810

Abstract

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.

Authors 5

1. Ineke D.C. Jansen

   Academic Center for Dentistry Amsterdam · Vrije Universiteit Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands

2. Socrates E. Papapoulos Aachen Center for Bone Quality Department of Internal Medicine division of Endocrinology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Center for Bone Quality Department of Internal Medicine division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

3. Nathalie Bravenboer

   Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Clinical Chemistry, Amsterdam University Medical Center, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands

4. Teun J. de Vries

   Academic Center for Dentistry Amsterdam · Vrije Universiteit Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands

5. Natasha M. Appelman‐Dijkstra corresponding Aachen Center for Bone Quality Department of Internal Medicine division of Endocrinology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Center for Bone Quality Department of Internal Medicine division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands