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Metabolomic studies identify true responders from non-responders to vitamin D supplementation in postmenopausal women
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Abstracts / Bone 44 (2009) S339–S450
studies with short durations of follow-up may be misleading for estimation of 10-year absolute fracture risk. Longer studies with follow-up periods of at least 8 years are recommended to obtain sufficiently accurate estimates of 10-year fracture risk. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.215
P304 Femoral neck strength and type fracture A. Hoisetha,*, G. Singhb, K. Strømsøeb a Radiology, Sentrum Røntgeninstitutt, Oslo, Norway b Orthopedic, Aker University Hospital, Oslo, Norway In a multidisciplinary study a variety of potential risk factors in patients with femoral neck fractures or trochanteric fractures with age and gender matched controls. Here we address the fracture groups: Do biomechanical bone factors determine the type of facture? Females with neck or trochanteric fractures and controls were 56, 50, and 34; and males 22,15, and 23. Mean age for the 6 groups ranged from 80.6 to 83.5 years. In all subjects volumetric CT uptakes were performed in the lumbar spine, the pelvis, the proximal femur and in the femoral condyles. CT-slices were reconstructed axially in the middle of the lumbar vertebrae, in the trochanteric regions and in the femoral condyles. At the narrowest part of the femoral necks, slices were reconstructed perpendicularly to the long axis of the necks. Except for in the femoral condyles, calcified bone area, density and mass of cortical and cancellous bone as well as of integrated cancellous and cortical bone. In the neck inner and outer cortical diameters were measured. Also hip axis length was measured. In the condyles area, density and mass were measured without differentiating between cancellous and cortical bone. In the neck moment of inertia and the product bending strength (moment of inertia) ⁎ (cortical density) and buckling ratio were assessed. Except for some of the cancellous bone parameters and for all density parameters, there were highly significant differences between the genders and between fractured patients and controls. The same gender differences were found in the fracture groups and in the controls. For pooling of data from males and females, the parameters were therefore adjusted for gender differences. T-tests were the used to determine the parameter differences in the two fracture groups. Finally a logistic regression analysis was performed to assess combination of parameters that may contribute to the fracture type. The parameters tested were those mentioned above. Almost all parameters indicated somewhat greater bone strength in those with trochanteric fractures as compared to neck fractures, however, only bending strength of the neck showed a significant difference (p < 0.045). In logistic regression bending strength, hip axis length, cortical thickness, buckling ratio and knee bone mass were included in the model. We have found that factors associated with increased strength of the femoral neck favoured trochanteric fractures. However, bone mass and bone cross sectional areas were very strong risk factors for having any proximal femoral fracture and the practical usefulness of more detailed biomechanical factors is therefore unclear. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.216
P305 Metabolomic studies identify true responders from non-responders to vitamin D supplementation in postmenopausal women C. Moniza,*, T. Ongb, R. Chandraa, L. Boweya, C. Mugglestonea a Clinical Biochemistry, Kings College Hospital, London, UK b Biochemistry, University of Aberdeen, Aberdeen, UK
Background: Inconclusive studies showing fracture prevention from calcium and vitamin D supplementation in osteoporotic subjects and several reports showing high prevalence of hypovitaminosis D in the elderly population, suggest there may be genetic inter-individual variability in handling micronutrients. We therefore undertook a metabolomics study in morning fasting urine samples, in normal postmenopausal women before and after supplementation with calcium and vitamin D. We used serum parameters of calcium homeostasis to determine response and matched these with urinary patterns of unique metabolites determined by NMR spectroscopy. Methods: 112 postmenopausal women (69 ± 10 yrs) gave informed consent to giving a blood and morning fasting urine sample before and after 3 months. At entry they were age matched to receive either oral 800 U of vitamin D and 1200 mg calcium or no supplementation. Blood was taken for a biochemical profile to include calcium and albumin, vitamin D and PTH. Urinary calcium and creatinine were measured and putative NMR biomarkers were examined after filtration (molecular cut-off 10 kDa, centrifuged, freeze-dried and reconstituted in phosphate buffer made up with TMSP as internal standard. NMR spectra were recorded in triplicate in a fully automated manner on a Varian UNITY 400 MHz spectrometer using a proton NMR set-up operating at a temperature of 293 K. The spectra were processed using the standard Varian software and converted to a data file suitable for multivariate analysis applications (MVDA). Small differences of comparable signals in different NMR spectra were aligned and respective datasets were used for MVDA in Matlab (V6.5, The Mathworks, Natick MA, USA). Complete data was obtained in 47 subjects. Data was normalized in an appropriate way, centred and scaled. Results: Significant changes in calcium, PTH and Vit D, differentiated responders (22) from non-responders (14) and controls (11) at 3 months, despite good compliance. The NMR data show distinct patterns in distinguishing controls, responders and non-responders. More interestingly, segregation was recognisable even before treatment commenced. The preliminary analyses of the ‘NMR fingerprint’ suggest that folate and vitamin B metabolism are implicated in Ca/ VitD status and response to supplementation. Conclusions: Regarding deficiency and how micronutrients interact in this population would be premature without larger studies to include genetic polymorphisms. Nevertheless, there is tremendous potential to develop tests for patients who do not need (nor respond) to Ca/VitD supplementation and target those that do. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.217
P306 Distribution analysis of menopause type vs fractures pattern and correlation test of stiffness index versus fractures pattern of 1267 postmenopausal women from Naples V. Lattea, C. Latteb,*, G. Monteleonea, F. Guadalascarab a Ortopedia e Traumatologia, P.O. S.Paolo Centro prevenzione e cura dell'osteoporosi Napoli, Italy b Clinica Ortopedica, Seconda Università Di Napoli, Napoli, Italy Background: Fragility fractures, both vertebral and non-vertebral (hip, wrist, rib, etc.) are caused by osteoporosis and represent an important cause of disability and mortality in elderly population, therefore a quick an reliable diagnosis is really important to early identify osteoporotic people. QUS Method (Achilles Express GE Lunar, Madison USA) is a valid alternative to DEXA Method and is characterized by easy and quickness of performances. Aims: The aim of this study is to confirm the validity of QUS Method as a diagnostic tool to predict fragility fractures risk in a population sample from Naples. We also analyzed the population
Abstracts / Bone 44 (2009) S339–S450
studies with short durations of follow-up may be misleading for estimation of 10-year absolute fracture risk. Longer studies with follow-up periods of at least 8 years are recommended to obtain sufficiently accurate estimates of 10-year fracture risk. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.215
P304 Femoral neck strength and type fracture A. Hoisetha,*, G. Singhb, K. Strømsøeb a Radiology, Sentrum Røntgeninstitutt, Oslo, Norway b Orthopedic, Aker University Hospital, Oslo, Norway In a multidisciplinary study a variety of potential risk factors in patients with femoral neck fractures or trochanteric fractures with age and gender matched controls. Here we address the fracture groups: Do biomechanical bone factors determine the type of facture? Females with neck or trochanteric fractures and controls were 56, 50, and 34; and males 22,15, and 23. Mean age for the 6 groups ranged from 80.6 to 83.5 years. In all subjects volumetric CT uptakes were performed in the lumbar spine, the pelvis, the proximal femur and in the femoral condyles. CT-slices were reconstructed axially in the middle of the lumbar vertebrae, in the trochanteric regions and in the femoral condyles. At the narrowest part of the femoral necks, slices were reconstructed perpendicularly to the long axis of the necks. Except for in the femoral condyles, calcified bone area, density and mass of cortical and cancellous bone as well as of integrated cancellous and cortical bone. In the neck inner and outer cortical diameters were measured. Also hip axis length was measured. In the condyles area, density and mass were measured without differentiating between cancellous and cortical bone. In the neck moment of inertia and the product bending strength (moment of inertia) ⁎ (cortical density) and buckling ratio were assessed. Except for some of the cancellous bone parameters and for all density parameters, there were highly significant differences between the genders and between fractured patients and controls. The same gender differences were found in the fracture groups and in the controls. For pooling of data from males and females, the parameters were therefore adjusted for gender differences. T-tests were the used to determine the parameter differences in the two fracture groups. Finally a logistic regression analysis was performed to assess combination of parameters that may contribute to the fracture type. The parameters tested were those mentioned above. Almost all parameters indicated somewhat greater bone strength in those with trochanteric fractures as compared to neck fractures, however, only bending strength of the neck showed a significant difference (p < 0.045). In logistic regression bending strength, hip axis length, cortical thickness, buckling ratio and knee bone mass were included in the model. We have found that factors associated with increased strength of the femoral neck favoured trochanteric fractures. However, bone mass and bone cross sectional areas were very strong risk factors for having any proximal femoral fracture and the practical usefulness of more detailed biomechanical factors is therefore unclear. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.216
P305 Metabolomic studies identify true responders from non-responders to vitamin D supplementation in postmenopausal women C. Moniza,*, T. Ongb, R. Chandraa, L. Boweya, C. Mugglestonea a Clinical Biochemistry, Kings College Hospital, London, UK b Biochemistry, University of Aberdeen, Aberdeen, UK
Background: Inconclusive studies showing fracture prevention from calcium and vitamin D supplementation in osteoporotic subjects and several reports showing high prevalence of hypovitaminosis D in the elderly population, suggest there may be genetic inter-individual variability in handling micronutrients. We therefore undertook a metabolomics study in morning fasting urine samples, in normal postmenopausal women before and after supplementation with calcium and vitamin D. We used serum parameters of calcium homeostasis to determine response and matched these with urinary patterns of unique metabolites determined by NMR spectroscopy. Methods: 112 postmenopausal women (69 ± 10 yrs) gave informed consent to giving a blood and morning fasting urine sample before and after 3 months. At entry they were age matched to receive either oral 800 U of vitamin D and 1200 mg calcium or no supplementation. Blood was taken for a biochemical profile to include calcium and albumin, vitamin D and PTH. Urinary calcium and creatinine were measured and putative NMR biomarkers were examined after filtration (molecular cut-off 10 kDa, centrifuged, freeze-dried and reconstituted in phosphate buffer made up with TMSP as internal standard. NMR spectra were recorded in triplicate in a fully automated manner on a Varian UNITY 400 MHz spectrometer using a proton NMR set-up operating at a temperature of 293 K. The spectra were processed using the standard Varian software and converted to a data file suitable for multivariate analysis applications (MVDA). Small differences of comparable signals in different NMR spectra were aligned and respective datasets were used for MVDA in Matlab (V6.5, The Mathworks, Natick MA, USA). Complete data was obtained in 47 subjects. Data was normalized in an appropriate way, centred and scaled. Results: Significant changes in calcium, PTH and Vit D, differentiated responders (22) from non-responders (14) and controls (11) at 3 months, despite good compliance. The NMR data show distinct patterns in distinguishing controls, responders and non-responders. More interestingly, segregation was recognisable even before treatment commenced. The preliminary analyses of the ‘NMR fingerprint’ suggest that folate and vitamin B metabolism are implicated in Ca/ VitD status and response to supplementation. Conclusions: Regarding deficiency and how micronutrients interact in this population would be premature without larger studies to include genetic polymorphisms. Nevertheless, there is tremendous potential to develop tests for patients who do not need (nor respond) to Ca/VitD supplementation and target those that do. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.217
P306 Distribution analysis of menopause type vs fractures pattern and correlation test of stiffness index versus fractures pattern of 1267 postmenopausal women from Naples V. Lattea, C. Latteb,*, G. Monteleonea, F. Guadalascarab a Ortopedia e Traumatologia, P.O. S.Paolo Centro prevenzione e cura dell'osteoporosi Napoli, Italy b Clinica Ortopedica, Seconda Università Di Napoli, Napoli, Italy Background: Fragility fractures, both vertebral and non-vertebral (hip, wrist, rib, etc.) are caused by osteoporosis and represent an important cause of disability and mortality in elderly population, therefore a quick an reliable diagnosis is really important to early identify osteoporotic people. QUS Method (Achilles Express GE Lunar, Madison USA) is a valid alternative to DEXA Method and is characterized by easy and quickness of performances. Aims: The aim of this study is to confirm the validity of QUS Method as a diagnostic tool to predict fragility fractures risk in a population sample from Naples. We also analyzed the population