Osteoporos Int (2014) 25:583–652 DOI 10.1007/s00198-014-2892-1
IOF Regionals–5th Asia-Pacific Osteoporosis Meeting Poster Presentations
# International Osteoporosis Foundation and National Osteoporosis Foundation 2014
P100 ADVERSE EFFECTS OF COMBINATION BREAST CANCER CHEMOTHERAPY ON BONE AND BONE MARROW C. Fan1,*, K. R. Georgiou1, R. A. McKinnon1,2, D. M. Keefe1,3,4, P. R. Howe5, C. J. Xian1 1 University of South Australia, 2Flinders University, 3SA Health, 4University of Adelaide, Adelaide, 5University of Newcastle, Callaghan, Australia Aims: Breast cancer is the most common cancer in the women of developed countries. The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among HER-2 positive breast cancer patients. Cyclophosphamide + epirubicin + 5-fluorouracil (CEF) and adriamycin/ doxorubicin + cyclophosphamide (AC) are two of the most commonly used chemotherapy regimens for treating breast cancer nowadays due to better survival with less toxicity involved. Despite the increasing use of CEF and AC protocols, their potentials in causing adverse skeletal effects remain unclear. Using female rat models mimicking the clinical settings, this study examined the effects of CEF and AC treatments on bone and bone marrow in the long bones. Methods: Female adult rats received 6 cycles (once weekly/ cycle) of either water or CEF intravenous injections consisting of 10 mg/kg cyclophosphamide, 2.5 mg/kg epirubicin and 10 mg/kg 5-flurouracil, or 4 cycles of AC intravenous injections consisting of 20 mg/kg cyclophosphamide and 2 mg/kg doxorubicin. Results: Both CEF and AC treatments were found to reduce trabecular bone volume at the metaphysis, which was associated with increases in the number and size of osteoclasts being formed from the bone marrow cells ex vivo, suggesting increased bone resorption following breast cancer chemotherapy. Moreover, a severe depletion of haematopoietic marrow cellularity was observed following both CEF and AC
treatments, which was accompanied by an increase in bone marrow adiposity. Conclusions: This study indicates that multiple cycles of CEF or AC breast cancer chemotherapy can induce some trabecular bone loss, but more severe bone marrow cell depletion and adiposity. Mechanisms for these combination breast cancer chemotherapy-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigations. Acknowledgements: This project was funded in parts by the National Health Medical Research Council (NHMRC) Australia and the University of South Australia.
P101 DELETERIOUS DIFFERENTIAL EFFECTS OF HIGH FAT DIET ON SKELETAL AND METABOLIC RESPONSES IN GONADECTOMIZED FEMALE AND MALE MICE J. Gautam1,* D. Choudhary, V. Khedgikar, P. Kushwaha, S. Adhikary, A. Karvande, N. Ahmad, R. Trivedi 1 Division of Endocrinology, Central Drug Research Institute, Lucknow, India Aims: Sex hormone deficiency during growth and aging is pivotal in the pathogenesis of bone fragility as well as metabolic disorders. Here we explored how high fat diet affects bone biology and metabolic syndrome related disorders in sex steroid deficient males and females differentially. Methods: C57BL/6 J ovariectomized (OVX) and orchidectomized (ORX) mice were randomized to receive a standard chow or a high-fat diet (HFD) (10 mice per group) for 10 weeks. Body weight gain, glucose metabolism, skeletal and biochemical parameters, osteogenic and adipogenic potential of bone marrow stromal cells (BMSCs), mRNA expressions in bone, effect on various tissues through histology were assessed.
Results: ORX mice on HFD showed higher weight gain compared to OVX mice on HFD, both gonadectomized (GX) mice on HFD gained weight predominately in the form of abdominal adipose tissue due to an increase in adipocyte size. Both GX mice on a HFD showed impaired glucose tolerance, with more pronounced intolerance in ORX mice compared to OVX mice fed with HFD. ORX mice on HFD showed significantly higher levels of triglyceride and low levels of HDL, while these levels remained unchanged in OVX chow vs. OVX HFD mice. However, OVX mice on HFD showed greater loss at trabecular bone than ORX mice on HFD, as assessed through μCT. BMSCs obtained from ORX and OVX mice on HFD showed favored progression of progenitors towards adipogenic lineage than osteoblasts. ORX mice on HFD showed fatty liver and increased deposition of glycogen granules and collagen in kidney than OVX mice on HFD. mRNA expressions revealed strong inhibitory effect on key osteoblastic genes with enhanced expression of bone resorptive and adipogenic genes in both GX mice on HFD. Conclusions: Our findings suggests that ovariectomy induced estrogen loss with HFD comparably induces more deteriorated bone microarchitecture in females than HFD supplemented orchidectomized males, while obesity epidemic is more obvious in orchidectomized males. References: Gautam J et al., Br J Nutr 2014;111:1811. Acknowledgements: We gratefully acknowledge the University Grant Commission (UGC), New Delhi, India for the award of research fellowships. Financial support from BSC0103 (New approaches towards understanding disease dynamics and accelerate drug discovery) is acknowledged.
P102 EVALUATION OF A NEW PREVENTION DEDICATED OSTEOSYNTHESIS DEVICE INDICATED TO PREVENT HIP FRACTURE M. Szpalski1,*, L. Jean-Charles2, F. Sibilla3, S. Costes3, J. Rigal2, C. Vienney4 1 Iris South Hospitals, Brussels, Belgium, 2Université Bordeaux Hospital, Pellegrin Hospital, Bordeaux, 3Centre Hospitalier de Libourne, Libourne, 4Hyprevention, Pessac, France Aims: The second fracture of the upper part of the femur is associated to a dramatic increase of the mortality rate (from 20 to 50 % depending of the studies). Therefore, it is clearly important to prevent this second fracture. The purpose of this study is to evaluate the impact of a new prevention dedicated osteosynthesis implant (PDOI) on patient in terms of safety and effectiveness.
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Methods: The study was performed in an on-going, prospective series of 15 PDOIs. To date, 3 patients were implanted. The PDOI was implanted into the contralateral hip during the same surgery time of fractured hip gamma nail implantation. Mean follow-up was 3 months. Clinical evaluation included the Oxford hip score, the WOMAC scores. Plantar pressure measurements were evaluated at 3 weeks and 3 months after the surgery using a Win-Pod (Medicapteurs). Results: Mean age and BMI of patients were 83±3 years and 25±9 kg/m2, respectively. Mean duration of surgery was 43 min (range 35–58). Cement quantities were similar over the 3 patients (6–7 cc). At 3 weeks, comparison between the two legs’ plantar pressures revealed no differences (50 %> 50 %). Experiences of pain were comparable between the two legs (0.7 and 1 for the gamma nail and the PDOI, respectively). At 3 months, WOMAC scores for pain and functionality were 6 and 36, respectively, and an OHS score of 25. Experiences of pain were similar between the two legs (3 and 4 for the gamma nail and the PDOI, respectively). Concerning the planar pressures, results obtained were in favor of the PDOI compared to the gamma nail (53 % vs. 47 %). No osteolysis or implant loosening was observed at the different follow-ups. Conclusions: At 3 months, patients have maintained good physical health without any inconveniences, in the contralateral hip, caused by the implantation of the PDOI. Furthermore, patients tend to more bear their weight on the leg with the PDOI. These first results are very encouraging and suggest that PDOI did not cause additional troubles or pains to the patient. Disclosure of Interest: C. Vienney Board Member of: Hyprevention
P103 THE RELATIONSHIP BETWEEN CYTOKINES LEVELS AND ARTERIAL STIFFNESS IN WOMEN WITH COMBINATION OF OSTEOPOROSIS AND IHD S. Tsarenok1,*, V. Gorbunov1, T. Aksenova1, L. Gagarkina1 1 Chita State Medical Academy, Chita, Russian Federation Aims: To reveal the relationship between cytokines levels and parameters of arterial stiffness in patients with osteoporosis comorbid with ischemic heart disease (IHD). Methods: 98 women with IHD (71.2±8.6 mean age) were investigated. The group 1, n=50, women with IHD, group 2, n=48, women with combination of IHD and osteoporosis. Serum levels of OPG, TGF-β, IL-1β, IL-4, IL-6, IL-8, IL10, TNF-α, soluble IL-1 receptor of the second type (ILsR II) and TNF (sTNFr) were determined by ELISA. Pulse wave velocity (PWV) in the carotid-femoral segment and central aortic pressure were performed by applanation tonometry by SphygmoCor, Australia. For statistical analysis we used WaldWolfowitz criteria. Correlation analysis was performed using
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gamma correlation and Spearman correlation. The study was based on GCP principles. Results: The serum level of IL-1, IL-4 was similar in the examined groups. Increased levels of IL-6 (4.67±7.17 vs. 5.55±5.27 p=0.0005), IL-8 (29.0±33.3 vs. 31.74± 40.9 p=0.0000), TNF-α (3.11±3.35 vs. 3.32±3.15* p= 0.008), IL-10 (7.25±12.52 vs. 9.9±17.42 p=0.01), OPG (37.0±23.5 vs. 50.7±38.6 p=0.016) were observed in women with comorbid disorders. Low levels of ILsR II (4050.3 ± 1186.9 vs. 3625.2 ± 1483.7 p = 0.0001) and sTNFr (0.129±0.101 vs. 0.103±0.114 p=0.00006) was found in group 2. Increased levels of central diastolic pressure C_DP (78.7 ± 9.5 75.4 ± 10.4 р = 0.01), pulse pressure C_PP (48.5±20.1 45.5±15.5 р=0.0000), mean pressure C_MP (96.9±15.4 93.7±12.7 р=0.0008) were determined in patients with combination of osteoporosis and IHD. The level of central systolic blood pressure C_SP was similar in the examined groups. Pulse wave velocity (PWV) for carotid-femoral segment in the first group was higher than in the control group (9.7±2.3 9.0 ±2.1 р=0.0000). Augmentation index (Alx) (24.9±9.1 25.8±8.8 р=0.0000) increase was found out in women with a combination of osteoporosis and IHD, significant differences of augmentation pressure (AP) were not found out between the examined groups (15.9 ± 9.5 14.9±8.0 р=0.1). A direct correlation between the presence of fractures, coronary atherosclerosis and the level of IL-10 and TNF–α was determined, as well as an inverse relationship between the presence of fractures, IHD and IL-8; the presence of IHD and levels of OPG. Serum IL-4 was correlated with C_SP (r = −0.24 p = 0.02), С_MP (r=−0.3 p=0.004), AP (r=0.21 p=0.04), Alx (r=0.26 p=0.01). The concentration of IL-6 was correlated with C_PP (r=0.37 p=0.02). sTNFr concentration was correlated with C_DP (r=0.36 p=0.02) and PWV (r=0.36 p=0.003). Conclusions: An increased level of IL-6, IL-8, IL-10, TNF-α, OPG and decreased the concentration of ILsR II and sTNFr was observed in women with comorbid pathology. Increased levels of PWV, C_DP, C_PP were determined in patients with combination of osteoporosis and IHD. Correlations between levels of cytokines and some parameters of arterial stiffness and the presence of fractures and coronary atherosclerosis are evident.
P104 THE EFFECTS OF METHYLGLYOXAL ON THE OPG/RANKL SYSTEM OF PREOSTEOBLAST MC3T3E1 CELL LINE I. Z. Akbar1,*, B. Setiawan2 1 Orthopaedic and Traumatology, 2Medical Chemistry and Biochemistry, Research Center for Osteoporosis, Medical
Faculty Lambung Mangkurat University, Banjarmasin, Indonesia Aims: This study aimed to elucidate whether long term exposures of methylglyoxal will affect the OPG/RANKL system in MC3T3E1 preosteoblast cell line. Methods: MC3T3E1 preosteoblast cell line was obtained from American Type Culture Cell. After confluency, preosteoblast MC3T3E1 cell line was exposed by methylglyoxal on several concentrations (2.5 and 5 μM) for 24 h (long term). We performed three replications in each group. The levels of OPG, RANKL, and OPG/RANKL ratio were analyzed by ELISA technique. Analysis of variance test was used to analyze the difference levels of OPG, RANKL, and OPG/RANKL ratio. Results: The levels of OPG was not significantly different between groups (P>0.05). The receptor activator of NF-κβ ligand levels was not significantly different between groups (P>0.05). In addition, the level of OPG/RANKL ratio was not significantly different between groups (P>0.05). Conclusions: Our study suggested that there is no effect of long term exposure of methylglyoxal on the OPG/RANKL system in the MC3T3E1 preosteoblast cell line. From these finding we speculate that the cytotoxicity effects of methylglyoxal may not involve the OPG/RANKL system. References: Akbar IZ et al., Oxid Antioxid Med Sci 2013; 2:65. Akbar IZ et al., Gulhane Med J 2014;56:93. Acknowledgements: The author acknowledges to all technicians (Mrs. H.N. Karima and Ms. C. Chotimah) in Central Laboratory of Life Science University of Brawijaya, Malang for helping this experiment.
P105 THE EFFECTS OF EUCHEUMA COTTONII ON THE OPG/RANKL SYSTEM OF MALE RAT FED HIGH-FAT DIET EXPOSED TO COAL DUST B. Setiawan1,*, N. Kania2, R. Leonas3, Z. Noor4 1 Medical Chemistry and Biochemistry, 2Pathology, Research Center for Osteoporosis, Ulin General Hospital, Medical Faculty Lambung Mangkurat University, Banjarmasin, 3Orthopaedic and Traumatology, Moh. Hoesin General Hospital, Faculty of Medicine, University of Sriwijaya, Palembang, 4 Orthopaedic and Traumatology, Research Center for Osteoporosis, Ulin General Hospital, Medical Faculty Lambung Mangkurat University, Banjarmasin, Indonesia Aims: This study aimed to elucidate whether Eucheuma cottonii treatment will modify the OPG/RANKL system in male rats fed a high-fat diet exposed to particulate matter 10 (PM10) coal dust. Methods: 36 male Wistar rats were randomly divided into six groups. Rats were fed a normal diet (nonexposed group), a
high-cholesterol diet for 12 weeks (HF control group), a highcholesterol diet followed by exposed to 12.5 mg/m3 of PM10 coal dust an hour daily in the last 4 weeks (HFD) weeks, the HFD group received the ethanolic extract of Eucheuma cottonii at doses 150 mg/kg BW (HFDA); 300 mg/kg BW (HFDB); and 600 mg/kg BW (HFDC). The levels of OPG, RANKL, and OPG/RANKL ratio were analyzed by ELISA technique. This study was approved by the Local Ethics Committee, Medical Faculty, Lambung Mangkurat University, Banjarmasin. Results: The level of OPG was not significantly different between groups (P>0.05). The receptor activator of NF-κβ ligand levels was not significantly different between groups (P>0.05). In addition, the levels of OPG/RANKL ratio was not significantly different between groups (P>0.05). Conclusions: There is no effect of ethanolic extract of Eucheuma cottonii on the OPG/RANKL system of atherosclerosis rats exposed to coal dust. References: Setiawan B et al., Med Sci I Int J 2013;12. Setiawan B et al., J Exp Integr Med 2013;3:219. Kania N et al., Cukurova Med J 2013;38:547. Kania N et al., J Toxicol 2013;2013:528146.
P106 THE EFFECTS OF CHRONIC INHALATION COMBINED CIGARETTE SMOKE AND PARTICULATE MATTER 10 (PM10) OF COAL DUST ON THE OPG/RANKL SYSTEM IN MALE RATS Z. Noor1,*, N. Kania2, R. Leonas3, B. Setiawan4 1 Orthopaedic and Traumatology, 2Pathology, Research Center for Osteoporosis, Ulin General Hospital, Medical Faculty Lambung Mangkurat University, Banjarmasin, 3Orthopaedic and Traumatology, Moh. Hoesin General Hospital, Faculty of Medicine, University of Sriwijaya,, Palembang, 4Medical Chemistry and Biochemistry, Research Center for Osteoporosis, Medical Faculty Lambung Mangkurat University, Banjarmasin, Indonesia Aims: This study aimed to elucidate whether chronically inhalation combined cigarette smoke and particulate matter 10 (PM10) of coal dust will affect the OPG/RANKL system in male rats. Methods: Twenty-four male Wistar rats were randomly divided into four groups; one noninhaled group (control) and three combined cigarette smoke and coal dust exposed groups (concentration 6.25, 12.5, and 25 mg/m3/h/day for 6 months). The levels of OPG, RANKL, and OPG/RANKL ratio were analyzed by ELISA technique. Analysis of variance test was used to analyze the difference levels of OPG, RANKL, and OPG/RANKL ratio. This study was approved by Local Ethics Committee, Medical Faculty, Lambung Mangkurat University, Banjarmasin.
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Results: The level of OPG was not significantly different between groups (P>0.05). The receptor activator of NF-κβ ligand levels was not significantly different between groups (P>0.05). In addition, the levels of OPG/RANKL ratio was not significantly different between groups (P>0.05). Conclusions: There is no effects of chronically inhalation combined cigarette smoke and particulate matter 10 (PM10) of coal dust on the OPG/RANKL system in male rats. References: Noor Z, Setiawan B, J Exp Integr Med 2013;3:69. Noor Z, Setiawan B, J Exp Integr Med 2013;3:153. Kania N et al., Cukurova M J 2013;38:547. Acknowledgements: The author thank to PT. Carsurin Banjarmasin, South Kalimantan for providing coal dust in diameter 0.05). The receptor activator of NF-κβ ligand levels was not significantly different between groups (P>0.05). In addition, the levels of OPG/ RANKL ratio was not significantly different between groups (P>0.05).
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Conclusions: There is no effects of acute particulate matter 10 (PM10) of coal dust on the OPG/RANKL system in middleaged male rats. References: Noor Z, Setiawan B, J Exp Integr Med 2013;3:69. Noor Z, Setiawan B, J Exp Integr Med 2013;3:153. Kania N et al., Cukurova Med J 2013;38:547.
P108 CONTENT OF TOXIC ELEMENTS IN THE BLOOD AND HAIR SAMPLES FROM THE NORTH D. S. Aganov1,*, V. V. Tyrenko1, E. N. Tsygan1, M. M. Toporkov1 1 Faculty of Therapy, Military Medical Academy n.a. S.M. Kirov, Saint Petersburg, Russian Federation Aims: Minerals are key elements of the most important chemical processes in the human body. Bone belongs to the most mineralized tissues. Accumulation of toxic elements in the body can lead to the development - disruption of the bone mineral metabolism. Our goal is to assess the content of toxic and essential elements in hair samples and blood serum in the north. Methods: A total of 99 people under the age of 50 years. There were included 63 people living in the north in the group I. Group II - 36 living in the northwest. Mass spectrometry with inductively coupled plasma was measured content 10 of toxic elements (Al, Cd, Ni, Hg, Rb, Pb, Ag, Sr, Tl, Ce) and 13 of essential elements (Na, Mg, P, Ca, V, Cr, Mn, Co, Cu, Zn, As, Se, I) in serum, as well as 12 of toxic elements (Al, Cd, Ni, Hg, Rb, Pb, Ag, Sr, Tl, Ce, Ba, Be) and 19 of essential elements (Na, Mg, P, Ca, V, Cr, Mn, Co, Cu, Zn, As, Cd, Se, I, B, K, Ba, Li, Fe) in hair samples. Results: Group I samples revealed increasing hair: barium (95 %), nickel (22 %), aluminum (9 %), cadmium (4 %) and strontium (4 %). Serum observed an increase of rubidium (18 %), cadmium (9 %) and mercury (4 %). In Group II, we observed a high nickel content (3 %) in hair samples. More pronounced changes are observed among the essential elements in a sample of hair, where deficiency of selenium was detected (100 %), iodine (90 %), cobalt (90 %), identified as a significant reduction in magnesium (55 %), copper (20 %), and zinc (35 %). Serum also revealed deficiency of selenium (90 %) and iodine (38 %). Despite the fact that the median calcium content in hair samples from northern residents are within the boundaries of the reference range, a number of surveyed found their reduced levels compared with the control group. Conclusions: Thus the inhabitants of the north, we are seeing a significant violation of the element status, characterized by a high content of barium, nickel, aluminum, cadmium, strontium, mercury, rubidium, lead.
Against the background of the excess of toxic elements observed reduced levels of essential elements necessary for the formation and bone metabolism. P109 DEPENDENCE OF BODY MASS INDEX AND OSTEOPENIC SYNDROME IN EXTREME CONDITIONS OF THE NORTH D. S. Aganov1,*, V. V. Tyrenko1, M. M. Toporkov1, E. N. Tsygan1 1 Military Medical Academy n.a. S.M. Kirov, Saint-Petersburg, Russian Federation Aims: In the north, people experiencing complex effects associated with exposure to adverse factors, which leads to the development of disorders of mineral metabolism. Our study aimed to explore the dependence of bone mass and osteoporosis in people living in the north. Methods: Military Medical Academy conducted a study of BMD in 63 men living in the north of Russia (Murmansk) aged 18–50 years by DXA at the X-ray bone densitometer (Osteometer DTX 200). The study excluded patients with a history of fractures available and chronic diseases. Evaluation of the results was carried out on BMD Z-score, a decrease in bone mass below the value ≤ −2.0, regarded as osteoporosis. Also we measured the height and weight. During the study formed three groups according to BMI: the first group 19.5–25.9 (norm), the second group 26.0–27.9, which corresponded to overweight and third group - BMI 28. Results: As a result of densitometric examination revealed a reduction in BMD Z-score ≤ −2.0 in 17 (26.9 %) of the test. Patients with normal BMD was 69.9 %. Under normal BMI low BMD were observed in 17 (26.9 %; p