Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers

Abstract

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9–79.1), range 50.0–96.6 yr; 574 women, median age 65.5 yr (58.1–75.4), range 50.1–94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2–13.2) and 10.9(6.3–11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00–2.37; 1.90, 1.18–3.05; 2.15, 1.26–3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34–5.29) and adjusted (2.03, 1.01–4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07–2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74–2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.

Uso de antihipertensivos como factor protector para fractura no traumática de cadera

“…Los mecanismos subyacentes de la asociación entre el uso IECA y ARA con el riesgo de fractura sustentan en que el eje angiotensina aldosterona puede provocar osteoporosis y podría afectar al sistema RANKL/RANK/OPG para ajustar el metabolismo óseo. La actividad del eje también puede ejercer varios otros bien conocidos factores de riesgo de osteoporosis o modalidades de tratamiento (16) . Se ha revelado la preservación del hueso cortical en mujeres y hombres mayores que usan tiazidas.…”

“…Los mecanismos subyacentes de la asociación entre el uso de los inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas de los receptores de la angiotensina (ARA) con el riesgo de fractura sustentan que el eje angiotensina aldosterona puede provocar osteoporosis y podría afectar también al sistema intercelular proteico del ligando del receptor activador del factor nuclear κB (RANKL), del sistema del receptor activador del factor nuclear-kB (RANK) y de la osteoprotegerina (OPG), o sistema RANKL/RANK/OPG, para ajustar el metabolismo óseo. Así mismo, la actividad del eje también puede ejercer otros bien conocidos factores de riesgo de osteoporosis o modalidades de tratamiento (16) .…”