Estrogen Deficiency Impairs Osseointegration in Hypertensive Rats Even Treated with Alendronate Coated on the Implant Surface

Abstract

Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we evaluated the effect of systemic antihypertensive and local alendronate coted on implants on osseointegration under hypertensive and estrogen-deficiency conditions. A total of 64 spontaneously hypertensive rats (SHRs) treated with losartan were randomly divided according to the estrogen-deficiency induction by ovariectomy (OVX) or not (SHAM), and whether the implant surface was coated with sodium alendronate (ALE) or not, resulting in four groups: SHR SHAM, SHR SHAM ALE, SHR OVX, and SHR OVX ALE. The removal torque, microcomputed tomography, and epifluorescence microscopy were the adopted analyses. The hypertensive and estrogen-deficiency animals presented a lower removal torque even when treated with alendronate on implant surface. The microcomputed tomography revealed a higher bone volume and bone-to-implant contact in the SHRs than the SHR OVX rats. Epifluorescence showed a decreased mineral apposition ratio in the SHR OVX ALE group. The data presented indicate that estrogen deficiency impairs osseointegration in hypertensive rats; in addition, alendronate coated on the implant surface does not fully reverse this impaired condition caused by estrogen deficiency.

Analysis of peri-implant bone tissue between hydrophilic and rough implant surfaces in spontaneously hypertensive rats treated with losartan

“…Studies done with the same experimental template demonstrated a lower quality of newly formed bone tissue in the area of bone-implant contact in spontaneously hypertensive rats (SHR), as well as the positive effects of losartan on the same area when these animals were treated. 9 , 10 , 21 As for the given antihypertensive, there was an improvement in some parameters for the losartan control group (COL NEO and COL ACQ), confirming the favorable effect of its vasodilator action on the peri-implant repair process. 20 , 21 …”

“… 9 , 10 , 21 As for the given antihypertensive, there was an improvement in some parameters for the losartan control group (COL NEO and COL ACQ), confirming the favorable effect of its vasodilator action on the peri-implant repair process. 20 , 21 …”

“…That means that while rough (NEO) surface showed better stability in SHRs, the hydrophilic (ACQ) surface associated with losartan (SHRL ACQ) offered greater and better implant removal torque when compared to all subgroups, corroborating findings in which spontaneously hypertensive rats treated with losartan obtained better results when compared to hypertensive groups and control. 9 , 10 , 21 Another study showed that at 15 postoperative days, the hydrophilic surface provided better biomechanics in the tibias of rats grafted with synthetic material (BoneCeramic - Straumann ® ) to the detriment of the same grafted area with the same material but with the installation of machined surface implants. 18 In contrast, another study using the same surfaces, but with the installation of implants in rabbit tibias, showed that there was no difference in removal torque at 14 and 28 postoperative days.…”

“…After 28 days (42 days after the implants were installed), the alizarin red fluorochrome (20 mg/kg) was injected into the animals. 21 , 23 , 24 Both fluorochromes indicate, respectively, the deposition of old bone and newly formed bone.…”

“…Finally, values for bone-implant contact (region of interest) were analyzed and defined in the CTAn software (Bruker MicroCT, Aartselaar, Belgium) in the following standard configurations: bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). 21 , 23 , 24 …”