hypolipemiant medication and bone remodeling author: orsan diana petruta coauthors: dodu roxana,...

HYPOLIPEMIANT MEDICATION AND BONE REMODELING

AUTHOR: ORSAN DIANA PETRUTACOAUTHORS: DODU ROXANA, TODERIC ANA-MARIA, TODERIC MARTACOORDINATORS: DR. SIPOS REMUS SEBASTIAN, PROF. DR. PAVAI ZOLTAN

INTRODUCTION

The role of hypolipemiant medication in bone remodeling is a subject that has sparked controversary.

Though some authors have demonstrateed their action in the sense of stimulating osteogenesis, others have demonstrated a stimulations of bone resorbtion.

Bone remodeling balance is given by the balance between osteoblastic and osteoclastic activity and by the mode of action of statins and fibrates on them.

OBJECTIVE

The purpose of this paper is to demonstrate the hystologic mode of action of statins and fibrates on bone remodeling and callus process.

MATERIAL AND METHOD

For our experimental study we used Wistar female rats divided into 6 groups, half of them being ovariectomized and all suffered a mediodiaphysary fracture. Each group was treated with simvastatin, fenofibrate 10mg/kg daily or received no treatment respectively.

Bone structure and fracture healing were evaluated at 2, 4, 6 and 8 weeks post fracture by histological means, with haematoxylin-eosine staining.

RESULTS

Simvastatin has a more protective effect on osteoporotic bone than fenofibrate, but not on healthy bone.

At all moments, the ovariectomized groups showed thinner bone trabeculas. At two and four weeks after de beginning of the treatment, there were no histological differences inside the ovariectomized groups and inside the nonovariectomized groups.

Figure 1. Bone structure at 6 weeks. HE, 10x

At week six, group C1 (Fig. 1a) had better represented trabeculas than S1 (Fig. 1b), but similar with F1 (Fig. 1c). On the contrary, group S2 (Fig. 1e) has thicker trabeculas then C2 (Fig. 4d) and F2 (Fig. 1f), roughly equal with those seen in C1.

On the eighth week, S1 (Fig. 2b) bone was still weaker then C1 (Fig. 2a), but not rarefied, while C2 (Fig. 2d) had a rarefied trabecular system in comparison with C1 and S1. S2 (Fig. 2e) group showed thinner trabeculas, but a denser trabecular system. F1 group (Fig. 2c) was similar with C1, while F2 group (Fig. 2f) had about the same structure as the S2 group.

Figure 2. Bone structure at 8 weeks. HE, 10x

Simvastatin has a positive effect on fracture healing, but not fenofibrate

Figure 3. Two weeks post fracture. HE,

10x (a,c), 2x (b)

At two weeks post-fracture, there were no significant histological differences between the nonovariectomized groups (C1, S1, F1), the callus was fibrous in all groups. S2 group (Fig. 3b) had an increased cartilaginous tissue in comparison with C2 (Fig. 3a) and F2 group (Fig. 3c), where we had a predominance of fibrous tissue.

Differences between groups became obvious at six weeks post fracture. In the S1 groups (Fig. 4b), the fracture was healed and S2 showed an osteoid zone predominance. F1 (Fig. 4c) and C1 groups (Fig. 4a) had a fibrocartilaginous callus and F2 was at the most delayed step of fracture repair.

Figure 4. Six weeks post fracture. HE, 2x (a,c), 10x (b)

Figure 5. Eight weeks post fracture. HE, 10x

(a,d,e), 2x (b,c,f)

At eight weeks, the control groups C1 (Fig. 5a) and C2 (Fig. 5d) were not healed, with chondrohialin callus, both statin groups S1 (Fig. 5b) and S2 (Fig. 5e) had a bony callus, while fibrate groups F1 (Fig. 5c) and F2 (Fig. 5f) were still fibrocartilaginous.

CONCLUSIONS

Hypolipemiant treatment influences the fracture repair process. The positive effect of statins on this process is more important on the ovariectomized group, in contrast with fibrates which have an accentuated effect on the nonovariectomized group.