Angiotensin receptor blockers (ARBs) but not angiotensin converting enzyme inhibitors (ACE-Is) are associated with lower osteoclast activity and higher bone mineral density: Results from the TUDA study.

Abstract

The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD). Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications. In the ARB analysis (n = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm² (95 % CI 0.830-0.882) vs 0.837 (0.812-0.863), p = 0.005; total hip 0.937 g/cm² (0.909-0.965) vs 0.913 (0.886-0.941), p = 0.002; and lumbar spine 1.122 g/cm² (1.082-1.162) vs 1.087 (1.047-1.126), p < 0.001. In the ACE-I analysis (n = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (n = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87-3.41) vs 3.28 (3.01-3.55), p = 0.040. No association was found between ACE-I usage and TRACP5b. ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.