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Osteoporosis International

Published in:

01-04-2016 | Original Article

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

Authors: P. R. Oikonomidou, C. Casu, Z. Yang, B. Crielaard, J. H. Shim, S. Rivella, M. G. Vogiatzi

Published in: Osteoporosis International | Issue 4/2016

Abstract

Summary

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).

Introduction

PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.

Methods

Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2^V617F knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.

Results

Compared to wt, both JAK2^V617F and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P < 0.01) suggesting a more severe bone phenotype than JAK2^V617F. Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.

Conclusions

This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

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Title: Polycythemia is associated with bone loss and reduced osteoblast activity in mice
Authors: P. R. Oikonomidou
C. Casu
Z. Yang
B. Crielaard
J. H. Shim
S. Rivella
M. G. Vogiatzi
Publication date: 01-04-2016
Publisher: Springer London
Published in: Osteoporosis International / Issue 4/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3412-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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