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Untangling fracture risk in monoclonal gammopathy of undetermined significance : A population-based cohort study

Rögnvaldsson, Sæmundur ; Aspelund, Thor ; Thorsteinsdóttir, Sigrún ; Turesson, Ingemar LU ; Björkholm, Magnus ; Landgren, Ola and Kristinsson, Sigurður Yngvi (2021) In European Journal of Haematology 107(1). p.137-144
Abstract

Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population-based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden. Methods: Data on fractures, PN, and confounders were acquired from high-quality registers in Sweden. Results: Monoclonal gammopathy of undetermined significance and PN were... (More)

Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population-based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden. Methods: Data on fractures, PN, and confounders were acquired from high-quality registers in Sweden. Results: Monoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21-1.37; P <.001 and HR: 1.34; 95% CI: 1.16-1.55; P <.001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27-2.16; P <.001). Fractures were not associated with long-term risk of MGUS progression (HR: 1.08; 95% CI: 0.77-1.53; P =.64). Discussion: Based on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
bone disease, fractures, monoclonal gammopathy of undetermined significance, multiple myeloma, neuropathy
in
European Journal of Haematology
volume
107
issue
1
pages
8 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85107567350
  • pmid:33840154
ISSN
0902-4441
DOI
10.1111/ejh.13633
language
English
LU publication?
no
id
8c46d2ab-c5a9-407a-b749-0d124f240fe6
date added to LUP
2021-06-24 16:16:39
date last changed
2024-02-20 08:57:13
@article{8c46d2ab-c5a9-407a-b749-0d124f240fe6,
  abstract     = {{<p>Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population-based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden. Methods: Data on fractures, PN, and confounders were acquired from high-quality registers in Sweden. Results: Monoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21-1.37; P &lt;.001 and HR: 1.34; 95% CI: 1.16-1.55; P &lt;.001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27-2.16; P &lt;.001). Fractures were not associated with long-term risk of MGUS progression (HR: 1.08; 95% CI: 0.77-1.53; P =.64). Discussion: Based on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS.</p>}},
  author       = {{Rögnvaldsson, Sæmundur and Aspelund, Thor and Thorsteinsdóttir, Sigrún and Turesson, Ingemar and Björkholm, Magnus and Landgren, Ola and Kristinsson, Sigurður Yngvi}},
  issn         = {{0902-4441}},
  keywords     = {{bone disease; fractures; monoclonal gammopathy of undetermined significance; multiple myeloma; neuropathy}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  pages        = {{137--144}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Haematology}},
  title        = {{Untangling fracture risk in monoclonal gammopathy of undetermined significance : A population-based cohort study}},
  url          = {{http://dx.doi.org/10.1111/ejh.13633}},
  doi          = {{10.1111/ejh.13633}},
  volume       = {{107}},
  year         = {{2021}},
}