Background and Objectives: It has been extensively discussed that there is a lowering effect of Replacement Therapy on lipids and lipoproteins. Recent hypotheses relate the lipids and osteoporosis. Thus, there is a possibility that hormone therapy improves osteoporosis not only via direct effect of estrogens on bone tissue, but also via lowering the lipids that may have detrimental effect on bone tissue. The aim of this study was to assess the effect of various regimens of hormone therapy on lipids and osteoporosis and the correlation between lipids and osteoporosis under given hormone treatment.

Methods: Three hundred and thirty five women (n=335) participated in this open study and were assigned to receive orally (a) CEE (n=29), (b) Tibolone (n=75), (c) CEE/MPA (n=57), (d) E2/NETA (n=72), (e) raloxifene (n=64) and (f) no therapy (control) (n=68) for at least 12 months. At baseline and 12 months blood samples were taken and analyzed for lipids and lipoproteins (total cholesterol, triglycerides, HDL, LDL, Lipoprotein (a), Apolipoprotein-A1, Apolipoprotein–B). At baseline and 12 months DEXA was also performed for the measurement of BMD of the lumbar spine.

Results: In the unopposed estrogen group (CEE) most of the variables were negatively connected with osteoporosis and BMD, but none of them were statistically significant. In the raloxifene group similar features were observed, but only LDL reached statistical significance (p=0.0031). In the tibolone group almost all variables were negatively correlated with osteoporosis and BMD, but again only LDL reached statistical significance (p=0.038). In the E2/NETA group most variables were negatively correlated with osteoporosis and BMD, but none reached statistical significance. In the CEE/MPA group all of the variables were negatively correlated with BMD and osteoporosis, but statistical significance was reached by total cholesterol, LDL and Lp(a) (p=0.008, 0.007, 0.047 respectively).

Conclusion: In this study it has been observed that there is a trend in almost every medication group towards an inverse correlation between lipids and BMD. The effect is more prominent in the tibolone, raloxifene and, mainly, in the CEE/MPA group. The greater effect was observed from the point of the lipids, in the LDL variable group. It is very important to clarify whether these findings could be extrapolated at orthopaedic trauma research providing thus a novel explanation for the aetiology of atrophic non unions in patients with compromised vascular function either locally or systematically.

Purpose: Athrophic non unions constitute a major problem in orthopaedic trauma. The main probably cause of atrophic non union is damage of the vascular system and dysfunctional regeneration of the vasculature at the area of the fracture. The most important hormonal pathway controlling angiogenesis is VEGF (Vascular Endothelial Growth Factor). The use of VEGF for enhancing bone healing in atrophic non unions could be a very promising solution for the future. An interesting alternative to the use of VEGF is the use of Erythropoietin (Epo). VEGF has been also reported to interact with Endothelial Progenitor Cells (EPCs). Our scope is to identify a possible new role for Epo as a valid substitute for VEGF through the clarification of the molecular and cellular pathways of fracture healing.

Methods: A survey was conducted via internet (Med-line - Pubmed, Cochrane database, Scopus) and relevant textbooks.

Results: It has been reported that Epo could induce increased chemotaxis, migration of Mesenchymal Stem Cells (MSCs), but also activation of Metaloproteinase - 9 and production of pro-angiogenic factors. These effects on MSCs could explain the observation that Epo could be very useful in the treatment of wound healing and burn healing in animal studies. It has been that Epo could express receptors at the chondrocytes, but also induce better bio-mechanical strength, callus formation, histomophometric image and increased bone density at the treated with Epo animals when compared with control animals. It is also worthy to note that the Epo has been found to stimulate neo-vascularisation in vivo, differentiation of endothelial cell lines towards a vascular pathway and improvement of cardiac function through EPCs and VEGF, implying Epo also in the differentiation and chemotaxis of the circulating EPCs. We should not forget that the transformation of EPCs in mesenchymal cells (i. g. myoblasts) has already been demonstrated.

Conclusions: The consequences of these observations could be very interesting: EPCs have been reported to enhance neo-vascularisation and angiogenesis at the region of the fracture. All these imply a novel role for EPCs in combination (or even replacing the rare) MSCs under the influence of VEGF and Epo for the enhancement of fracture vascularisation and healing enhancement. Further studies should clarify this new field in basic orthopaedic, trauma and bone metabolism science.