Losartan reverses impaired osseointegration in spontaneously hypertensive rats

Abstract

Objective: Hypertension is not only associated with cardiovascular diseases but also with alterations in bone quality. Hypertension therefore might be a risk factor for osseointegration. Preclinical studies suggest that losartan, an angiotensin II receptor blocker widely used to treat hypertension, has a beneficial effect in graft consolidation.
Here, we determine the effect of hypertension and losartan on osseointegration.

Methods: We used spontaneously hypertensive rats (SHR) and normotensive Wistar albinus rats receiving losartan (30 mg/kg, p.o.) or left untreated. After 1 week, titanium miniscrews were inserted into the tibia. Sixty days after implantation, implant stability was evaluated by removal torque measurement considered the primary endpoint.
Microcomputed tomography and histomorphometric analysis were secondary endpoints.

Results: Losartan increased the removal torque in the hypertensive SHR group to levels of the Wistar controls. While the cortical parameters of osseointegration remained unchanged, losartan increased medullary bone formation. Microcomputed tomography revealed a higher bone volume per tissue volume and trabecular thickness in the SHR rats treated with losartan. Histomorphometric analysis further showed that losartan significantly increased the thickness of newly formed bone in medullary area in hypertensive SHR rats. Losartan did not significantly alter the parameters of osseointegration in normotensive rats.

Conclusions: The data presented suggest that the angiotensin II receptor antagonist losartan increases the medullary parameters of osseointegration in a tibia model of spontaneously hypertensive rats. Considering the study limitations, understanding the impact of hypertension and the respective drugs on osseointegration requires further research.

FIGURE 5 Histology of the cortical compartment. Histological pictures of the implant in the tibia, showing the cortical compartment of each group at a higher magnification. Plexiform bone, is observed in the periosteal region and the cortical compartment. Undecalcified thin‐ground sections, Levai–Laczko stained
FIGURE 6 Histology of the medullary compartment. Histological pictures of the implant in the tibia, depicting the medullary compartment of each group at a higher magnification. A thin layer mainly consisting of woven bone that had been partly remodeled characterized the bone formation in the medullary compartment. Signs of remodeling can be observed. Undecalcified thin‐ground sections, Levai–Laczko stained.

KEYWORDS
bone, losartan, osseointegration, renin‐angiotensin system, spontaneously hypertensive rats

Gabriel Mulinari-Santos, Fábio Roberto de Souza Batista, Franziska Kirchweger, Stefan Tangl, Reinhard Gruber, Roberta Okamoto6