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The prospective association between high-density lipoprotein (HDL) cholesterol and risk of incident fractures in the general population

Sutton, Richard LU ; Rogmark, Cecilia LU ; Fedorowski, Artur LU orcid ; Hamrefors, Viktor LU orcid and Johansson, Madeleine LU orcid (2025) In Osteoporosis International
Abstract
Summary
Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.

Purpose
Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density.

Methods
We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37%... (More)
Summary
Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.

Purpose
Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density.

Methods
We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37% women, mean follow-up 13 years). Fracture endpoints were identified through national registers. Follow-up was from 2002 until the first episode of incident fracture or end of follow-up December 31, 2020. The primary and secondary outcomes were total incident fractures and incident fractures of the hip and lower limb, respectively.

Results
Incident fractures occurred in 26% (n = 4,710) of all subjects (mean follow-up of 13 years). Subjects with incident fractures had higher HDL-C levels (mmol/L ± standard deviation) compared with subjects without fractures (1.5 ± 0.4 vs. 1.4 ± 0.4 mmol/L). In multivariate regression analysis, higher HDL-C levels were associated with increased risk of total incident fractures in the general population (HR 1.12, 95%CI 1.03–1.22, p = 0.006), and in men (HR 1.18, 95%CI 1.04–1.35, p = 0.02). No statistically significant relationship was found in women or between incident fractures of hip and lower limb fractures (p > 0.05).

Conclusions
Higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men from the general population but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Osteoporosis International
publisher
Springer
external identifiers
  • pmid:41171459
ISSN
1433-2965
DOI
10.1007/s00198-025-07732-6
language
English
LU publication?
yes
id
61b7d7db-e5fa-4aa5-89ca-9f040233577d
alternative location
https://link.springer.com/10.1007/s00198-025-07732-6
date added to LUP
2025-10-31 12:15:54
date last changed
2025-11-03 08:09:14
@article{61b7d7db-e5fa-4aa5-89ca-9f040233577d,
  abstract     = {{Summary<br/>Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.<br/><br/>Purpose<br/>Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density.<br/><br/>Methods<br/>We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37% women, mean follow-up 13 years). Fracture endpoints were identified through national registers. Follow-up was from 2002 until the first episode of incident fracture or end of follow-up December 31, 2020. The primary and secondary outcomes were total incident fractures and incident fractures of the hip and lower limb, respectively.<br/><br/>Results<br/>Incident fractures occurred in 26% (n = 4,710) of all subjects (mean follow-up of 13 years). Subjects with incident fractures had higher HDL-C levels (mmol/L ± standard deviation) compared with subjects without fractures (1.5 ± 0.4 vs. 1.4 ± 0.4 mmol/L). In multivariate regression analysis, higher HDL-C levels were associated with increased risk of total incident fractures in the general population (HR 1.12, 95%CI 1.03–1.22, p = 0.006), and in men (HR 1.18, 95%CI 1.04–1.35, p = 0.02). No statistically significant relationship was found in women or between incident fractures of hip and lower limb fractures (p &gt; 0.05).<br/><br/>Conclusions<br/>Higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men from the general population but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.}},
  author       = {{Sutton, Richard and Rogmark, Cecilia and Fedorowski, Artur and Hamrefors, Viktor and Johansson, Madeleine}},
  issn         = {{1433-2965}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Osteoporosis International}},
  title        = {{The prospective association between high-density lipoprotein (HDL) cholesterol and risk of incident fractures in the general population}},
  url          = {{http://dx.doi.org/10.1007/s00198-025-07732-6}},
  doi          = {{10.1007/s00198-025-07732-6}},
  year         = {{2025}},
}