As part of the Ogliastra project, which focuses on the study of genealogical, genetic and clinical features of isolated populations of this area of Sardinia, we conducted a cross-sectional epidemiological study to estimate the prevalence, the environmental determinants and heritability of osteoporosis in ten villages. Ogliastra area is one of the most isolated and anciently populated region of Sardinia; its population has grown slowly and uniformly during the time with no relevant immigration and it is characterized by a great deal of homogeneity in life style and eating habits and a high rate of endogamy and consanguinity. The sample cohort consists of 6056 individuals (4166 women and 1890 men), aged 30-103. The voluntary participants gave a blood sample, underwent anthropometric measurements, bioelectrical impedance, Quantitative Ultrasonography (QUS) and a standardized interview collecting socio-demographic, lifestyle, medical and pharmacological history data and family history of osteoporosis. The T-score threshold for AD-SoS (Amplitude Dependent Speed of Sound) of -3.2 SD, was used to estimate the osteoporosis prevalence. Both AD-SoS and UBPI (Ultrasound Bone Profile Index) parameters were investigated because they provide different information on bone structure properties: AD-SoS being related mostly to density and UBPI to bone fragility. Overall osteoporosis prevalence is 11.4%, 17.0% in females and 5.2% in males. We checked for dissimilarities in prevalence of main risk factors for osteoporosis in the ten villages, but none substantial discrepancy was found. Notably, differences in osteoporosis prevalence were found among villages, especially between the two closest ones: Talana (10.5% in men and 24.6% in women) and Urzulei (2.7% in men and 6.9% in women). This may reflect the presence of different founders and genetic background. Both QUS parameters resulted significantly correlated to anthropometric and bioimpedance measures: the negative impact of weight, BMI and fat mass can be ascribed to the effect of soft tissue, even if it has been observed only for AD-SoS. This result suggests a possible influence of local adiposity on AD-SoS, as UBPI is not influenced by soft tissue. High fractions of lean, muscular and body cell masses and high phase angles seem to be protective factors, whereas fat mass and extra cellular water appear as risk factors for osteoporosis. Among blood serum parameters Alkp showed a weak significant inverse relationship with QUS measurements while calcium, phosphorus, SGOT and GPT resulted to have negligible correlations. In women age at menarche, number of pregnancies and months since menopause are inversely correlated to AD-SoS and UBPI, even if, when age-adjusted, age at menarche becomes directly related to QUS measures as in our sample mean age at menarche is higher in older age classes. Then we constructed multiple models for both AD-SoS and UBPI putting all the significant variables. Covariates, all significant at the 0.05 level, explain 58% of AD-SoS variability and 60% of UBPI variability. Heritability estimates were obtained using SOLAR software: we run variance component models on 45 extended pedigrees, each up to 4 generations deep, adjusting for the associated covariates. Global heritability was 35.3% for Ad-SoS and 43.5% for UBPI. Some conclusions can be safely drawn: risk factors usually associated to DXA-BMD and calcaneal QUS are also associated to phalangeal QUS parameters; prevalence of osteoporosis in Ogliastra population is comparable to that of Italy and Europe; a large part of variances of AD-SoS and UBPI were found to be attributable to genetic factors. Furthermore, the advantageous features of these genetic isolates and the differences found among the ten villages encourage us to deepen the study looking for genetic variants predisposing to osteoporosis.
Genetic and environmental determinants of hand Quantitative ultrasound in Sardinian isolated Populations
G Biino;S Vaccargiu;M Pirastu
2009
Abstract
As part of the Ogliastra project, which focuses on the study of genealogical, genetic and clinical features of isolated populations of this area of Sardinia, we conducted a cross-sectional epidemiological study to estimate the prevalence, the environmental determinants and heritability of osteoporosis in ten villages. Ogliastra area is one of the most isolated and anciently populated region of Sardinia; its population has grown slowly and uniformly during the time with no relevant immigration and it is characterized by a great deal of homogeneity in life style and eating habits and a high rate of endogamy and consanguinity. The sample cohort consists of 6056 individuals (4166 women and 1890 men), aged 30-103. The voluntary participants gave a blood sample, underwent anthropometric measurements, bioelectrical impedance, Quantitative Ultrasonography (QUS) and a standardized interview collecting socio-demographic, lifestyle, medical and pharmacological history data and family history of osteoporosis. The T-score threshold for AD-SoS (Amplitude Dependent Speed of Sound) of -3.2 SD, was used to estimate the osteoporosis prevalence. Both AD-SoS and UBPI (Ultrasound Bone Profile Index) parameters were investigated because they provide different information on bone structure properties: AD-SoS being related mostly to density and UBPI to bone fragility. Overall osteoporosis prevalence is 11.4%, 17.0% in females and 5.2% in males. We checked for dissimilarities in prevalence of main risk factors for osteoporosis in the ten villages, but none substantial discrepancy was found. Notably, differences in osteoporosis prevalence were found among villages, especially between the two closest ones: Talana (10.5% in men and 24.6% in women) and Urzulei (2.7% in men and 6.9% in women). This may reflect the presence of different founders and genetic background. Both QUS parameters resulted significantly correlated to anthropometric and bioimpedance measures: the negative impact of weight, BMI and fat mass can be ascribed to the effect of soft tissue, even if it has been observed only for AD-SoS. This result suggests a possible influence of local adiposity on AD-SoS, as UBPI is not influenced by soft tissue. High fractions of lean, muscular and body cell masses and high phase angles seem to be protective factors, whereas fat mass and extra cellular water appear as risk factors for osteoporosis. Among blood serum parameters Alkp showed a weak significant inverse relationship with QUS measurements while calcium, phosphorus, SGOT and GPT resulted to have negligible correlations. In women age at menarche, number of pregnancies and months since menopause are inversely correlated to AD-SoS and UBPI, even if, when age-adjusted, age at menarche becomes directly related to QUS measures as in our sample mean age at menarche is higher in older age classes. Then we constructed multiple models for both AD-SoS and UBPI putting all the significant variables. Covariates, all significant at the 0.05 level, explain 58% of AD-SoS variability and 60% of UBPI variability. Heritability estimates were obtained using SOLAR software: we run variance component models on 45 extended pedigrees, each up to 4 generations deep, adjusting for the associated covariates. Global heritability was 35.3% for Ad-SoS and 43.5% for UBPI. Some conclusions can be safely drawn: risk factors usually associated to DXA-BMD and calcaneal QUS are also associated to phalangeal QUS parameters; prevalence of osteoporosis in Ogliastra population is comparable to that of Italy and Europe; a large part of variances of AD-SoS and UBPI were found to be attributable to genetic factors. Furthermore, the advantageous features of these genetic isolates and the differences found among the ten villages encourage us to deepen the study looking for genetic variants predisposing to osteoporosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
