Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPAR gamma

Abstract

Aims: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPAR gamma partial agonist, has been used for to treat hypertension. It is known that PPAR gamma activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPAR gamma protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. Main methods: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPAR gamma protein expression in the bones. Key findings: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPAR gamma levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). Significance: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPAR gamma. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.