Sickle Cell Hemoglobinopathies and Bone Heath

SCD is a hereditary disease arising only when two parents carrying sickle cell trait (SCT) conceive a child. SCT is clinically silent but very common in African Americans with a ~10% prevalence, although most carriers are unaware of their status. There are no data on bone mineral density (BMD) or vitamin D status in these individuals. Although it is clear that those with SCD have accelerated bone thinning the effect of SCT on bone metabolism or fractures has not been studied. Although the incidence of hip fracture in AA women is about half that of white women, the etiology and risk factors of fractures in AA women are not clearly defined, and it is intriguing to postulate that SCT may have a relationship to bone metabolism and fracture risk in this population, and thus contribute to racial disparity. We hypothesize that the mechanisms underlying altered bone homeostasis in SCD are different than in the general population but perhaps similar to those with SCT. We also hypothesize that SCT is a state of reduced bone mineralization which may contribute to racially disparate outcomes among AAs with bone fractures. Our objectives are (1) to define the mechanisms of bone loss in SCD and (2) to evaluate parameters of bone metabolism in human subjects with SCT compared to those with normal hemoglobin and those with SCD. We will investigate the effect of SCD and SCT on bone homeostasis in premenopausal AA subjects via serum bone turnover markers, calciotrophic hormones and bone mineral density (BMD) testing. We hypothesize that premenopausal AA women with SCT will have significantly lower BMD and higher serum bone turnover markers than race- and age-matched control AA women. In addition, we will explore Vitamin D status and its relationship to bone turnover and BMD in all three groups. We further postulate that bone homeostasis in SCT subjects will be intermediate between healthy controls and subjects with SCD.