Antibody Response to Paramyxoviruses in Paget\u2019s Disease of Bone

Micaela Rios Visconti,Ricardo Usategui-Martín,Stuart H Ralston

doi:10.1007/s00223-017-0265-4

Abstract

Paget’s disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. Genetic factors play a central role in the pathogenesis of PDB but environmental factors also contribute. Measles virus (MV), respiratory syncytial virus (RSV) and canine distemper virus (CDV) have all been implicated as potential disease triggers but the data are conflicting. Since chronic paramyxovirus infection with measles is known to be accompanied by increased production of antiviral antibodies, we have analysed circulating concentrations of antibodies to MV, CDV, and RSV as well as mumps, rubella and varicella zoster virus (VZV) in 463 patients with PDB and 220 aged and gender-matched controls. We also studied the relation between viral antibody concentrations and various markers of disease severity and extent in 460 PDB patients. A high proportion of cases and controls tested positive for antiviral antibodies but there was no significant difference in circulating antibody concentrations between PDB cases and controls for MV, CDV, RSV, rubella or VZV. However, mumps virus antibody levels were significantly higher in the PDB cases (mean ± SD = 3.1 ± 0.84 vs. 2.62 ± 0.86. p < 0.001). There was no association between disease severity and circulating antibody concentrations to any of the viruses. In conclusion, we found no evidence to suggest that PDB is associated with abnormalities of immune response to measles or other paramyxoviruses, although there was evidence of a greater antibody response to mumps. The results do not support that hypothesis that PDB is associated with a persistent infection with measles or other paramyxoviruses.

Highlights

Paget’s disease of bone is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover at one or more skeletal sites [1]
A high proportion of Paget’s disease of bone (PDB) cases and controls tested positive for measles virus, rubella, varicella zoster virus (VZV), mumps and respiratory syncytial virus (RSV) indicating previous infection, with no significant difference between the groups
Antibodies were detected that cross-reacted with distemper virus in about 45% of PDB cases and controls with no difference between the groups

Summary

Introduction

Paget’s disease of bone is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover at one or more skeletal sites [1]. Current evidence suggests that genetic factors play a key role in susceptibility [4], but there is a strong environmental component evidenced by the fact that the disease has become less common and less severe in several countries over recent decades [5,6,7]. Several potential environmental triggers for Paget’s disease of bone (PDB) have been suggested including dietary calcium intake [8], vitamin D deficiency [9] and excessive biomechanical loading of affected bones [10], but the most widely studied is paramyxovirus infection [11, 12]. Some researchers have reported finding evidence of measles virus (MV) nucleic acids or antigens in cells and tissues from patients with the disease [17,18,19,20].

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