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The relationship among vitamin B12, homocysteine and bone mineral density in vegetarian and nonvegetarian women
Abstracts / Bone 44 (2009) S234–S252
OP09 The regulation of energy metabolism — Bone metabolic activity connection is gender-specific B. Buday*, E. Kulcsár, L. Botond, É. Péterfai, L. Korányi Metabolism, DRC, Balatonfüred, Hungary Background: Osteocalcin connects bone formation to energy metabolism and to insulin production and sensitivity in mice via the adipocyte derived adiponectin. This finding suggests that in humans a gender specific connection should exist as circulating adiponectin levels are significantly higher in females than in males. Methods: The relationship between insulin sensitivity, osteocalcin and bone state in 35 healthy (20 females, 25 males), and 92 glucose intolerant (51 females, 41 males) subjects was examined. Body composition, bone density and glucose utilization (M value for insulin sensitivity) measured by hyperinsulinemic normoglycemic clamp were determined separately in males and females. Bone markers were used for measuring the activity of the bone metabolic units [BMU index = (β-crosslaps× catepsin-K ×sRANKL) ×(OPG× P1NP) − 1] to characterize bone resorption/formation. Results: Bone resorption/formation and osteocalcin levels were similar in the two genders, however both were lower in glucose intolerant men than in healthy men (osteocalcin: 24.5 ± 11 vs. 18.1 ± 9 ng/ml, p < 0.05, BMU index: 0.021 ± 0.02 vs 0.008 ± 0.01, p < 0.05). In the healthy group, we found a positive correlation between osteocalcin and muscle glucose utilisation (M value; females: r = + 0.319, p < 0.05, males: r = +0.481, p < 0.01), although this relationship disappeared in glucose intolerant groups. The BMU index showed strong correlation with muscle M values only in females regardless of the status of glucose metabolism (healthy: r = +0.638, p < 0.001, glucose intolerant: r = +0.390, p < 0.01). Osteocalcin or BMU index did not show correlation with adiponectin level in any of the genders. Based on a multivariate regression analysis, in all females significant independent predictors of osteocalcin level were fasting blood glucose, whole and lean body glucose utilization, metabolic clearance rate, estradiol and LDL-cholesterol levels (determined 92% of its value), while in all men osteocalcin were predicted by serum calcium, OGTT glucose area under the curve, free fatty acid levels, insulogenic index, HOMA-R and waist/hip ratio (determined 95% of its value). Conclusion: Our study has confirmed the relationship between insulin sensitivity and osteocalcin in a healthy human population, although we found basic differences between the two genders which difference is not related to osteocalcin. Our data also questions the role of adiponectin in the osteocalcin–energy metabolism axis in humans. Conflict of interest: None declared.
S239
Regular plasma and thrombocyte donors were enrolled in an open, observational, single-center, cross sectional study. We studied 1) the acute effects of platelet donation on acid–base balance and parameters of bone and mineral metabolism in 102 donors and 2) compared bone mineral density (BMD) at the lumbar spine and hip to 102 age-, sex- and BMI-matched controls (CTR). Apheresis led to significant decreases in Ca++ (−17%), phosphate (− 18%) and marked increases in PTH (+192%) and base excess (+57%) 1 h after initiation of apheresis (see also Fig. 1). At this time serum CTX were significantly raised and remained elevated the next morning. Baseline biochemical comparisons between donors and CTR revealed slightly but significantly lower values for the apheresis cohort regarding serum calcium, albumin, and 25-hydroxyvitamin D levels, as well as higher values for serum osteoprotegerin. Mean Z score at the lumbar spine adjusted for age, sex, BMI, average physical activity and daily calcium intake was lower for donors (− 0.28 ± 0.11) when compared to CTR (0.06 ± 0.11, P < 0.05). Total and femoral neck BMD was also lower for the donor group, however, this difference was not significant. Exposure to citrate during apheresis leads to marked acute effects on mineral and bone metabolism. Longer-term effects for some parameters were small but significant in this cross-sectional design. The results further show that regular donation of blood compounds leads to lower BMD values at the lumbar spine.
doi:10.1016/j.bone.2009.03.098
OP10 Apheresis affects bone and mineral metabolism, acid–base balance and bone density K. Amreina,*, C. Katschnigb, T.R. Piebera, E. Stacha, G. Lanzerc, S. Sipurzysnkic, H. Dobniga a Department of Internal Medicine, Medical University of Graz, Austria b Medical University of Graz, Division of Endocrinology and Nuclear Medicine, Austria c Medical University of Graz, University Clinic of Blood Group Serology and Transfusion Medicine, Graz, Austria Apheresis is a procedure to selectively obtain blood components. For anticoagulation, citrate is used. It effectively binds to ionized calcium (Ca++), thereby inhibits coagulation and leads to metabolic alkalosis. Whether regular apheresis affects bone and mineral metabolism is unknown.
Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.099
OP11 The relationship among vitamin B12, homocysteine and bone mineral density in vegetarian and nonvegetarian women Z. Krivosikovaa,*, V. Spustovaa, K. Stefikovaa, M. KrajcovicovaKudlackovab, M. Valachovicovab, T. Nemcovac, P. Blazicekd
S240
Abstracts / Bone 44 (2009) S234–S252
a
Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia b Department of Bioactive Compounds and Nutritional Screening, Slovak Medical University, Bratislava, Slovakia c Department of Public Health and Social Work, Trnava University, Trnava, Slovakia d Department of Clinical Biochemistry, Hospital of Ministry of Defence, Bratislava, Slovakia Introduction: Nutrition plays an important role in the acquisition and maintenance of skeletal integrity. There are some evidence that a well-balanced vegetarian diet may be consistent with good health and can potentially reduce the risk of several chronic diseases. On the other hand, people following a long-term vegetarian diet very often suffer from nutrient shortage like Ca, P, Fe, Zn, vitamin D or vitamin B12. The lack of vitamin B12 together with vitamin B6 and folate deficiency is close related to homocysteine (Hcy) metabolism. Hyperhomocysteinemia (HHcy) was found to be associated with increased bone turnover markers and increased fracture risk. Thus, Hcy, vitamin B12 and folate may be regarded as novel risk factors for micronutrient-deficiency-related osteoporosis. The aim of our study was to assess the possible impact of vegetarian diet on bone mass density in cohort of Slovak vegetarian women. Materials and methods: The study was performed on group of 141 women on long-term ovo-lacto-vegetarian diet and control group of 131 women on standard western diet. Standard biochemical analyses, plasma vitamin B12, folate and Hcy concentrations were measured. Bone mineral density (BMD) for lumbar spine (L1–L4), right femoral neck (FN), trochanter (Tr) and total of femur (ToFN) were measured with dual energy X-ray absorptiometry. Results: The mean Hcy levels were beyond the normal range in both groups (> 12.0 μmol/l) but significantly higher in vegetarians (p < 0.001). HHcy was found in 78% of vegetarians and in 48% of nonvegetarians. Vitamin B12 levels were significantly higher in nonvegetarians in both subgroups (p < 0.05) and inversely correlated with Hcy (r = −0., p < 0.001). Folate plasma levels were in normal range in all probands. Significant inverse correlations were found between Hcy and FN-BMD (r = −0.1887, p < 0.003), Tr-BMD (r = −0.1725, p < 0.01) and ToFN-BMD (r = −0.2053, p < 0.001). No correlations were confirmed in nonvegetarians when they were evaluated separately. Conclusion: Our results indicate a strong association between plasma Hcy levels and decreased BMD in vegetarians. It suggests that vegetarian women can be at higher risk for low BMD than nonvegetarian women. This work was supported by Research and Development Support Agency under the contract No: APVT-21-010104 a APVT-21-017704. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.100
OP12 Maternal vitamin D status determines volumetric bone mineral density of the newborn H.T. Viljakainena,*, E. Saarnioa, T. Hytinanttib, M. Miettinenc, H. Surceld, S. Anderssonb, K. Laitinene, C. Lamberg-Allardta a Department of Applied Chemistry and Microbiology, Nutrition, University of Helsinki, Finland b Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland c Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland d Department of Child and Adolescent Health, National Public Health Institute, Oulu, Finland e Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Vitamin D regulates 3% of the human genome, including effects on bone health throughout the life. Maternal vitamin D status may programme skeletal development. The objective of this study is to determine the association of maternal vitamin D status with volumetric bone mineral density of their newborn. Subjects and methods: Pregnant women (N = 98) participated in a semi cross-sectional study in a birth hospital in late autumn 2007. The mean (SD) values for age, body mass index before pregnancy, pregnancy weigh gain and total vitamin D intake, in mothers were 31 (4) years, 23.5 (3.7) kg/m2, 13.1 (4.3) kg and 14.3 (5.8) μg, respectively. The mean characteristics of the newborn birth weight, height, and duration of the pregnancy according to gender were for girls (N = 46) 3470 (480) g, 50 (2) cm, 283 (9) d and for boys (N = 52) 3680 (390) g, 51 (2) cm and 285 (8) d, respectively. Blood samples were collected from the mother during the first trimester and two days postpartum and from the umbilical cord at birth for the analysis of serum 25-hydroxy-vitamin D (25-OHD) and parathyroid hormone (PTH). Volumetric bone mineral density (BMD) was measured by pQCT at the 20% site of the newborn tibia on an average 10 (11) days postpartum. Bone contour was analyzed with a single threshold of 180 mg/mm3 for the detection of total bone BMD, BMC and CSA. Results: The mean S-25-OHD was 43.7 (14.5), 49.3 (14.3) and 50.8 (13.9) nmol/l, during first trimester, postpartum and in umbilical cord, respectively. The newborns were divided into two groups: low group with mean maternal vitamin D status below 42.6 nmol/l and high group with mean maternal vitamin D status at least 42.6 nmol/l. Mean maternal postpartum PTH was 3.38 (1.96) pmol/l, which correlated inversely with 25-OHD, r = −0.283, (p < 0.001). A correlation was found between maternal vitamin D status and newborn tibian CSA, r = 0.227, (p < 0.05). Newborn in the low group were heavier (p = 0.03) and 64% boys. Tibia BMC was found to be 0.046 (95% CI 0.010–0.081) g/cm higher (p = 0.01) and CSA 11.8 (95% CI 1.7–21.8) mm2 bigger (p = 0.02), but no difference in BMD, in the high group compared with the low group. These results were adjusted for newborn weight, height, gender, the durance of gestation and age at the measurement. Conclusions: Current Nordic recommendation is inadequate for pregnant women. Newborn with lower maternal vitamin D status had an average 13.5% lower BMC and 15.6% smaller CSA in tibia, but no difference in BMD compared to newborn with higher maternal vitamin D status. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.101
OP13 Synergistic inhibition of osteosarcoma cell growth by combination of RAD001 (everolimus) and zoledronic acid G. Moriceaua, B. Oryb, L. Mitrofanc, R. Briona, C. Charriera, P. Piletd, L. Shultze, J. Monkkonenc, F. Rédinia, D. Heymanna,* a Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes, France b Masschusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA c Department of Oharmaceutics, University of Kuopio, Kuopio, Finland d INSERM UMR 791 Centre Commun de Microscopie Electronique et de Microanalyse, CHU Hotel Dieu, Nantes, France e The Jackson Laboratory, Bar Harbor, Bar Harbor, USA Osteosarcoma is the most frequent malignant primary bone tumor that occurs mainly in the young, with an incidence peak observed at 18 years. Despite recent improvements in chemotherapy and surgery, the problem of non-response to chemotherapy remains and this poor prognosis warrants new therapeutic strategies to improve the overall
OP09 The regulation of energy metabolism — Bone metabolic activity connection is gender-specific B. Buday*, E. Kulcsár, L. Botond, É. Péterfai, L. Korányi Metabolism, DRC, Balatonfüred, Hungary Background: Osteocalcin connects bone formation to energy metabolism and to insulin production and sensitivity in mice via the adipocyte derived adiponectin. This finding suggests that in humans a gender specific connection should exist as circulating adiponectin levels are significantly higher in females than in males. Methods: The relationship between insulin sensitivity, osteocalcin and bone state in 35 healthy (20 females, 25 males), and 92 glucose intolerant (51 females, 41 males) subjects was examined. Body composition, bone density and glucose utilization (M value for insulin sensitivity) measured by hyperinsulinemic normoglycemic clamp were determined separately in males and females. Bone markers were used for measuring the activity of the bone metabolic units [BMU index = (β-crosslaps× catepsin-K ×sRANKL) ×(OPG× P1NP) − 1] to characterize bone resorption/formation. Results: Bone resorption/formation and osteocalcin levels were similar in the two genders, however both were lower in glucose intolerant men than in healthy men (osteocalcin: 24.5 ± 11 vs. 18.1 ± 9 ng/ml, p < 0.05, BMU index: 0.021 ± 0.02 vs 0.008 ± 0.01, p < 0.05). In the healthy group, we found a positive correlation between osteocalcin and muscle glucose utilisation (M value; females: r = + 0.319, p < 0.05, males: r = +0.481, p < 0.01), although this relationship disappeared in glucose intolerant groups. The BMU index showed strong correlation with muscle M values only in females regardless of the status of glucose metabolism (healthy: r = +0.638, p < 0.001, glucose intolerant: r = +0.390, p < 0.01). Osteocalcin or BMU index did not show correlation with adiponectin level in any of the genders. Based on a multivariate regression analysis, in all females significant independent predictors of osteocalcin level were fasting blood glucose, whole and lean body glucose utilization, metabolic clearance rate, estradiol and LDL-cholesterol levels (determined 92% of its value), while in all men osteocalcin were predicted by serum calcium, OGTT glucose area under the curve, free fatty acid levels, insulogenic index, HOMA-R and waist/hip ratio (determined 95% of its value). Conclusion: Our study has confirmed the relationship between insulin sensitivity and osteocalcin in a healthy human population, although we found basic differences between the two genders which difference is not related to osteocalcin. Our data also questions the role of adiponectin in the osteocalcin–energy metabolism axis in humans. Conflict of interest: None declared.
S239
Regular plasma and thrombocyte donors were enrolled in an open, observational, single-center, cross sectional study. We studied 1) the acute effects of platelet donation on acid–base balance and parameters of bone and mineral metabolism in 102 donors and 2) compared bone mineral density (BMD) at the lumbar spine and hip to 102 age-, sex- and BMI-matched controls (CTR). Apheresis led to significant decreases in Ca++ (−17%), phosphate (− 18%) and marked increases in PTH (+192%) and base excess (+57%) 1 h after initiation of apheresis (see also Fig. 1). At this time serum CTX were significantly raised and remained elevated the next morning. Baseline biochemical comparisons between donors and CTR revealed slightly but significantly lower values for the apheresis cohort regarding serum calcium, albumin, and 25-hydroxyvitamin D levels, as well as higher values for serum osteoprotegerin. Mean Z score at the lumbar spine adjusted for age, sex, BMI, average physical activity and daily calcium intake was lower for donors (− 0.28 ± 0.11) when compared to CTR (0.06 ± 0.11, P < 0.05). Total and femoral neck BMD was also lower for the donor group, however, this difference was not significant. Exposure to citrate during apheresis leads to marked acute effects on mineral and bone metabolism. Longer-term effects for some parameters were small but significant in this cross-sectional design. The results further show that regular donation of blood compounds leads to lower BMD values at the lumbar spine.
doi:10.1016/j.bone.2009.03.098
OP10 Apheresis affects bone and mineral metabolism, acid–base balance and bone density K. Amreina,*, C. Katschnigb, T.R. Piebera, E. Stacha, G. Lanzerc, S. Sipurzysnkic, H. Dobniga a Department of Internal Medicine, Medical University of Graz, Austria b Medical University of Graz, Division of Endocrinology and Nuclear Medicine, Austria c Medical University of Graz, University Clinic of Blood Group Serology and Transfusion Medicine, Graz, Austria Apheresis is a procedure to selectively obtain blood components. For anticoagulation, citrate is used. It effectively binds to ionized calcium (Ca++), thereby inhibits coagulation and leads to metabolic alkalosis. Whether regular apheresis affects bone and mineral metabolism is unknown.
Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.099
OP11 The relationship among vitamin B12, homocysteine and bone mineral density in vegetarian and nonvegetarian women Z. Krivosikovaa,*, V. Spustovaa, K. Stefikovaa, M. KrajcovicovaKudlackovab, M. Valachovicovab, T. Nemcovac, P. Blazicekd
S240
Abstracts / Bone 44 (2009) S234–S252
a
Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia b Department of Bioactive Compounds and Nutritional Screening, Slovak Medical University, Bratislava, Slovakia c Department of Public Health and Social Work, Trnava University, Trnava, Slovakia d Department of Clinical Biochemistry, Hospital of Ministry of Defence, Bratislava, Slovakia Introduction: Nutrition plays an important role in the acquisition and maintenance of skeletal integrity. There are some evidence that a well-balanced vegetarian diet may be consistent with good health and can potentially reduce the risk of several chronic diseases. On the other hand, people following a long-term vegetarian diet very often suffer from nutrient shortage like Ca, P, Fe, Zn, vitamin D or vitamin B12. The lack of vitamin B12 together with vitamin B6 and folate deficiency is close related to homocysteine (Hcy) metabolism. Hyperhomocysteinemia (HHcy) was found to be associated with increased bone turnover markers and increased fracture risk. Thus, Hcy, vitamin B12 and folate may be regarded as novel risk factors for micronutrient-deficiency-related osteoporosis. The aim of our study was to assess the possible impact of vegetarian diet on bone mass density in cohort of Slovak vegetarian women. Materials and methods: The study was performed on group of 141 women on long-term ovo-lacto-vegetarian diet and control group of 131 women on standard western diet. Standard biochemical analyses, plasma vitamin B12, folate and Hcy concentrations were measured. Bone mineral density (BMD) for lumbar spine (L1–L4), right femoral neck (FN), trochanter (Tr) and total of femur (ToFN) were measured with dual energy X-ray absorptiometry. Results: The mean Hcy levels were beyond the normal range in both groups (> 12.0 μmol/l) but significantly higher in vegetarians (p < 0.001). HHcy was found in 78% of vegetarians and in 48% of nonvegetarians. Vitamin B12 levels were significantly higher in nonvegetarians in both subgroups (p < 0.05) and inversely correlated with Hcy (r = −0., p < 0.001). Folate plasma levels were in normal range in all probands. Significant inverse correlations were found between Hcy and FN-BMD (r = −0.1887, p < 0.003), Tr-BMD (r = −0.1725, p < 0.01) and ToFN-BMD (r = −0.2053, p < 0.001). No correlations were confirmed in nonvegetarians when they were evaluated separately. Conclusion: Our results indicate a strong association between plasma Hcy levels and decreased BMD in vegetarians. It suggests that vegetarian women can be at higher risk for low BMD than nonvegetarian women. This work was supported by Research and Development Support Agency under the contract No: APVT-21-010104 a APVT-21-017704. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.100
OP12 Maternal vitamin D status determines volumetric bone mineral density of the newborn H.T. Viljakainena,*, E. Saarnioa, T. Hytinanttib, M. Miettinenc, H. Surceld, S. Anderssonb, K. Laitinene, C. Lamberg-Allardta a Department of Applied Chemistry and Microbiology, Nutrition, University of Helsinki, Finland b Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland c Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland d Department of Child and Adolescent Health, National Public Health Institute, Oulu, Finland e Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Vitamin D regulates 3% of the human genome, including effects on bone health throughout the life. Maternal vitamin D status may programme skeletal development. The objective of this study is to determine the association of maternal vitamin D status with volumetric bone mineral density of their newborn. Subjects and methods: Pregnant women (N = 98) participated in a semi cross-sectional study in a birth hospital in late autumn 2007. The mean (SD) values for age, body mass index before pregnancy, pregnancy weigh gain and total vitamin D intake, in mothers were 31 (4) years, 23.5 (3.7) kg/m2, 13.1 (4.3) kg and 14.3 (5.8) μg, respectively. The mean characteristics of the newborn birth weight, height, and duration of the pregnancy according to gender were for girls (N = 46) 3470 (480) g, 50 (2) cm, 283 (9) d and for boys (N = 52) 3680 (390) g, 51 (2) cm and 285 (8) d, respectively. Blood samples were collected from the mother during the first trimester and two days postpartum and from the umbilical cord at birth for the analysis of serum 25-hydroxy-vitamin D (25-OHD) and parathyroid hormone (PTH). Volumetric bone mineral density (BMD) was measured by pQCT at the 20% site of the newborn tibia on an average 10 (11) days postpartum. Bone contour was analyzed with a single threshold of 180 mg/mm3 for the detection of total bone BMD, BMC and CSA. Results: The mean S-25-OHD was 43.7 (14.5), 49.3 (14.3) and 50.8 (13.9) nmol/l, during first trimester, postpartum and in umbilical cord, respectively. The newborns were divided into two groups: low group with mean maternal vitamin D status below 42.6 nmol/l and high group with mean maternal vitamin D status at least 42.6 nmol/l. Mean maternal postpartum PTH was 3.38 (1.96) pmol/l, which correlated inversely with 25-OHD, r = −0.283, (p < 0.001). A correlation was found between maternal vitamin D status and newborn tibian CSA, r = 0.227, (p < 0.05). Newborn in the low group were heavier (p = 0.03) and 64% boys. Tibia BMC was found to be 0.046 (95% CI 0.010–0.081) g/cm higher (p = 0.01) and CSA 11.8 (95% CI 1.7–21.8) mm2 bigger (p = 0.02), but no difference in BMD, in the high group compared with the low group. These results were adjusted for newborn weight, height, gender, the durance of gestation and age at the measurement. Conclusions: Current Nordic recommendation is inadequate for pregnant women. Newborn with lower maternal vitamin D status had an average 13.5% lower BMC and 15.6% smaller CSA in tibia, but no difference in BMD compared to newborn with higher maternal vitamin D status. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.101
OP13 Synergistic inhibition of osteosarcoma cell growth by combination of RAD001 (everolimus) and zoledronic acid G. Moriceaua, B. Oryb, L. Mitrofanc, R. Briona, C. Charriera, P. Piletd, L. Shultze, J. Monkkonenc, F. Rédinia, D. Heymanna,* a Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes, France b Masschusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA c Department of Oharmaceutics, University of Kuopio, Kuopio, Finland d INSERM UMR 791 Centre Commun de Microscopie Electronique et de Microanalyse, CHU Hotel Dieu, Nantes, France e The Jackson Laboratory, Bar Harbor, Bar Harbor, USA Osteosarcoma is the most frequent malignant primary bone tumor that occurs mainly in the young, with an incidence peak observed at 18 years. Despite recent improvements in chemotherapy and surgery, the problem of non-response to chemotherapy remains and this poor prognosis warrants new therapeutic strategies to improve the overall