Leila Kolios

Effects of isoflavones equol and genistein on bone quality in a rat osteopenia model.

Phytoestrogens might be an alternative medication in prophylaxis and treatment of osteoporosis. In this study, the osteoprotective effects of genistein (GEN) and equol (EQO) were evaluated. After ovariectomy, 44 rats received soy‐free food (Control, C) and developed substantial osteoporosis over the course of two months. After that period, the rats were divided into different groups and fed estradiol (E), GEN or EQO for 35 days. To analyze the osteoprotective effects of the tested substances, bone biomechanical properties and histomorphometric changes of the lumbar vertebrae were evaluated.

Effects of black cohosh (Cimicifuga racemosa) and estrogen on metaphyseal fracture healing in the early stage of osteoporosis in ovariectomized rats.

Osteoporosis and its accompanying, predominantly metaphyseal, fractures are a major health problem. Black cohosh (Cimicifuga racemosa) and estrogen positively influence osteoporotic bone. Both substances may improve fracture healing in early osteoporosis as well. In 48 twelve-week-old ovariectomized or, respectively, sham-operated (SHAM) rats, a standardized metaphyseal tibia osteotomy with bridging T-plate fixation was performed. During the healing process of 35 days, rats received soy-free (SHAM, osteopenic C), estrogen- (E) or Cimicifuga racemosa- (CR) supplemented diets. After sacrifice, the callus formation was analyzed with regard to biomechanical quality, morphology, quantity, time course of new bone built and gene expression. CR induced a high rate of metaphyseal callus formation. The biomechanical properties and the amount of new callus formation indicated that fracture healing was still in progress. Therefore, gene expression of osteoblasts was comparatively high. Body weight and the trabecular structure were influenced little by CR. Estrogen improved the biomechanical properties of the callus. Resistance to microfracturing was significantly enhanced in the E group and even superior to SHAM. Remodeling of the callus formation had already begun. The trabecular network and the typical endosteal fracture healing were especially improved. Osteoporotic metaphyseal fracture healing was improved by estrogen more than by Cimicifuga racemosa. The process of fracture healing occurred nearly physiologically. The generation of callus formation was supported by Cimicifuga racemosa as well, but the five-week duration of application was too short for Cimicifuga racemosa to show its complete potential. Already-initiated Cimicifuga racemosa therapy for menopausal symptoms could be continued during fracture healing without hesitation.

Equol but not Genistein Improves Early Metaphyseal Fracture Healing in Osteoporotic Rats

Healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Hormone replacement therapy could improve fracture healing, but, because of its potential side effects, natural alternatives are more appealing. The aim of this study was to determine if the soy metabolite equol and the native isoflavone genistein, in comparison to 17beta-estradiol, improve metaphyseal fracture healing in ovariectomy-induced osteoporotic bone of the rat. Forty-eight 12-week-old female rats developed severe osteoporosis ten weeks after ovariectomy. After metaphyseal tibial osteotomy and standardized stable internal fixation, changes in callus morphology were evaluated biomechanically, qualitatively and quantitatively in fluorochrome-labeled histological sections and microradiographs in ovariectomized rats (C) and under standardized 17beta-estradiol (E), equol (EQ) and genistein (G) supplemented rats over a period of five weeks. Estrogen and equol were able to improve the elasticity of callus formation significantly in postmenopausal osteoporotic bone (stiffness of C: 121.40 +/- 47.08 N/mm, E: 147.90 +/- 39.38 N/mm, EQ: 167.8 +/- 59.90 N/mm). The effects of estrogen were more anabolic than those of equol and were visible in changes to the trabecular bone (N.Nd of E: 6.47 +/- 7.68, EQ: 4.25 +/- 3.96). However, in terms of the whole body, equol seemed to induce less of an adverse reaction than estrogen (body weight of C: 342.20 +/- 19.91 g, E: 280.25 +/- 12.05 g, EQ: 308.75 +/- 24.28 g). Genistein as an osteoclast inhibitor influenced callus stiffness (G: 144.50 +/- 61.52 N/mm) and negatively impacted trabecular structure (N.Nd of G: 0.59 +/- 1.01) in severely osteoporotic bones. Estrogen and equol were able to improve fracture healing in ovariectomy-induced osteoporotic bones, and the extent of callus formation played only a minor role. Genistein rather negatively influenced fracture healing. The metaphyseal osteotomy model in ovariectomized rats allows an accurate study of the therapeutic effects of antiosteoporotic substances on the fracture healing process.

Changes in the histomorphometric and biomechanical properties of the proximal femur of ovariectomized rat after treatment with the phytoestrogens genistein and equol.

The isoflavonoids found in soy have attracted great interest as dietary phytoestrogens that might be effective for postmenopausal hormone replacement therapy. Special attention has been devoted to the hormonal effects of various isoflavonoids, like genistein (GEN) and daidzeins (DAID) potent metabolite, equol (EQ). Here we aimed to investigate the short-term effects of genistein and equol on the proximal femur of ovariectomized (OVX) rats. Forty-eight, 3-month-old female Sprague-Dawley rats were ovarectomized; after eight weeks the bilateral osteotomy and osteosynthesis (OS) of their tibiae was performed and the rats were randomly divided into the following four groups: OVX control group (C), treated with estradiol-17beta (E2) -benzoate (E; daily intake 0.086 mg/d per animal), genistein (GEN; daily intake 12.7 mg/d per animal) and equol (EQ; daily intake 4.65 mg/d per animal). At 5 weeks postoperatively (OS), the breaking test was performed on the trochanteric region of femur. Additionally, histomorphometric assessment, and trabecular and cortical bone microstructure analyses were performed. The relative gain of body weight (BW) in the EQ (24 %) group was significantly (p < 0.05) lower than in the C (33 %) and GEN (30 %) groups. After treatment for 5 weeks, the maximal load (F(max)) and yield load (yL) were higher (p < 0.05 for the weight-adapted results) in the E (188.4 N resp. 113.1 N) and EQ (177.3 N resp. 112 N) groups as compared to C (162.8 N resp. 109.1 N) and GEN (165.7 N resp. 108.8 N). In the histomorphometric tests the E- (trabecular area (Tb.Ar) = 74.93 %, trabecular nodes/mm(2) (N.Nd/mm(2)) = 48.65) and EQ-treated (Tb.Ar = 63.13 %, N.Nd/mm(2) = 43.72) animals showed significant improvement with regard to Tb.Ar and trabecular connectivity (N.Nd./mm(2)) in comparison to C (Tb.Ar = 46.84, N.Nd/mm(2) = 31.86) and GEN (Tb.Ar = 48.22 %, N.Nd/mm(2) = 34.15). There were no differences in relative cortical width (Ct.Wi) among the four groups. The treatment with EQ resulted in improved biomechanical and histomorphometric properties as compared to the treatment with GEN. Thus, of the studied substances, EQ seems to be a possible alternative to hormone replacement therapy, but further studies are needed.

Cost analysis of Topical Negative Pressure (TNP) Therapy for traumatic acquired wounds.

Extended traumatic wounds require extended reconstructive operations and are accompanied by long hospitalizations and risks of infection, thrombosis and flap loss. In particular, the frequently used Topical Negative Pressure (TNP) Therapy is regarded as cost-intensive. The costs of TNP in the context of traumatic wounds is analyzed using the method of health economic evaluation. All patients (n=67: 45 male, 22 female; average age 54 y) with traumatically acquired wounds being treated with TNP at the university hospital of Goettingen in the period 01/01/2005–31/12/2007 comprise the basis for this analysis. The concept of activity-based costing based on clinical pathways according to InEK (National Institute for the Hospital Remuneration System) systematic calculations was chosen for cost accounting. In addition, a special module system adaptable for individual courses of disease was developed. The treated wounds were located on a lower extremity in 83.7% of cases (n=56) and on an upper extremity in 16.3% of cases (n=11). The average time of hospitalization of the patients was 54 days. Twenty-five patients (37.31%) exceeded the „maximum length of stay“ of their associated DRG (Diagnosis Related Groups). The total PCCL (patient clinical complexity level = patient severity score) of 2.99 reflects the seriousness of disease. For the treatment of the 67 patients, total costs were

Absence of positive effect of black cohosh (Cimicifuga racemosa) on fracture healing in osteopenic rodent model

1,729,922.32 (1,249,176.91 €). The cost calculation showed a financial deficit of

Effects of phytoestrogens and estrogen on fracture healing in severe experimental osteoporotic bone: Equol and estrogen improve — Genistein inhibits

–210,932.50 (–152,314.36 €). Within the entire treatment costs of

Effects of low-magnitude, high-frequency mechanical stimulation in the rat osteopenia model

218,848.07 (158,030.19 €), 12.65% per case were created by TNP with material costs of

Effect of human parathyroid hormone hPTH (1–34) applied at different regimes on fracture healing and muscle in ovariectomized and healthy rats

102,528.74 (74,036 €), representing 5.92% of entire costs. The cost of TNP per patient averaged

Improvement of Femoral Bone Quality After Low-Magnitude, High-Frequency Mechanical Stimulation in the Ovariectomized Rat as an Osteopenia Model

3,266.39 (2,358.66 €). The main portion of the costs was not – as is often expected – due to high material costs of TNP but instead to long-term treatments. Because of their complexity, the cases are insufficiently represented in the lump-sum calculation of the InEK. A differentiated integration of complex TNP-treatment in the DRG system (e.g., as an expanded DRG I98Z) would be a step towards cost recovery. In addition, the refunding of outpatient TNP-treatment would lead to enhanced quality of life for the patients and to a reduction of hospital costs and length of stay.