Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ.

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ 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 PPARγ 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 PPARγ 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 PPARγ. 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.

Bone mineral density is reduced by telmisartan in male spontaneously hypertensive rats.

BACKGROUND: Telmisartan, an angiotensin AT1 receptor blocker, and treadmill running were compared for their effects on bone mineral density (BMD) and biomechanical properties of male spontaneously hypertensive rats (SHR). It was hypothesized that running (18m/min/60min/d) and telmisartan (5mg/kg/d) would have a positive effect on bone parameters. METHODS: Three-month-old male SHRs were divided into three groups: sedentary (S), telmisartan (T), and exercise (E). At the end of an 8-week protocol, femur and lumbar vertebrae were analyzed by dual-energy X-ray absorptiometry (DXA) for bone mineral density and by the three-point bending test for biomechanical properties. Blood pressure in all groups was measured by a tail-cuff manometer. RESULTS: Telmisartan and treadmill running reduced blood pressure when compared to the sedentary group; however, telmisartan did not improve bone characteristics. Instead, it reduced BMD of femur total and lumbar vertebrae and worsened bone biomechanic properties. Treadmill running maintained bone characteristics and hence was effective in maintaining bone health. CONCLUSION: Results showed that telmisartan negatively affected bones suggesting that caution should be taken in possible therapeutic applications for protecting bone health in hypertensive conditions. More studies are necessary to clarify the mechanisms through which telmisartan favors bone loss in this model.