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Osteoporos Int. 2019 Jun 17. doi: 10.1007/s00198-019-05041-3. [Epub ahead of print]

The renin-angiotensin aldosterone system and osteoporosis: findings from the Women's Health Initiative.

Author information

1
Department of Medicine, Division of Rheumatology, J. Harold Harrison MD, Distinguished University Chair in Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA, USA. lcarbone@augusta.edu.
2
Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA. lcarbone@augusta.edu.
3
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4
Georgia Prevention Institute, Medical College of Georgia at Augusta University, Augusta, GA, USA.
5
Department of Medicine, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Bavaria, Germany.
6
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
7
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.

Abstract

New users of RAAS inhibitors, including ACE inhibitors and ARBs, have a small increased risk for fracture in the first 3 years of use, with a reduced risk of fracture with longer duration of use.

INTRODUCTION:

Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD).

METHODS:

The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women's Health Initiative over a minimum median follow-up of 6.5 years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements.

RESULTS:

There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3 years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3 years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use.

CONCLUSIONS:

In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3 years of use. However, long-term use (> 3 years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.

KEYWORDS:

Aging; Fracture; Medication; Postmenopausal

PMID:
31209511
DOI:
10.1007/s00198-019-05041-3

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