The risk of osteoporotic fracture, which affects millions of women in the United States, may be increased by the coexistence of chronic kidney disease (CKD). This interdisciplinary proposal will elucidate the effects of moderate CKD on bone mass, microarchitecture, and strength in the postmenopausal skeleton. We will use a cross-sectional, in-depth analysis of bone mineral density (BMD), microarchitecture, calciotropic hormones and biochemical markers of remodeling in women, with and without stage 3 CKD (60>GFR>30 ml/min) and with and without a history of fragility fracture. State of the art non-invasive techniques, high-resolution peripheral computed tomography (HRpQCT) and finite element analysis (FEA), will allow us to distinguish trabecular and cortical compartments, discern trabecular microstructural details and model bone strength. We will compare women with CKD to women with primary hyperparathyroism (PHPT) to further explore the effects of PTH on the postmenopausal skeleton. We hypothesize that bone microarchitecture and strength will differ based upon history of CKD and fracture;biochemical changes in women with CKD will be associated with abnormal microarchitecture and decreased strength;catabolic effects of PTH on cortical bone will be seen in women with CKD and PHPT.
The specific aims are: 1) to compare areal and volumetric measurements of bone mass and microarchitecture by HRpQCT in women by fracture history and CKD;2) to compare bone mechanical competence (strength) by FEA in women by fracture history and CKD;3) to assess relationships between microarchitecture and strength with PTH, other calciotropic hormones, and remodeling markers;and 4) to assess bone mass, microarchitecture, strength and biochemical characteristics in postmenopausal women with PHPT. This proposal includes a 5-year career development plan involving interdisciplinary mentorship and training in structural, biomechanical and biochemical assessment of bone quality, supported by formal coursework. The research and training described in this proposal will answer important questions in skeletal physiology while advancing my goal of becoming an independent investigator in the field of metabolic bone diseases.
This project will generate information about the impact of mild declines in kidney function on the skeleton in postmenopausal women. Our findings will increase awareness of unique factors that affect skeletal structure and strength in the rapidly increasing population of postmenopausal women with osteoporosis and CKD. They may emphasize the importance of incorporating CKD and secondary hyperparathyroidism into diagnostic and treatment strategies for postmenopausal osteoporosis.
|Sutter, Stephanie; Nishiyama, Kyle K; Kepley, Anna et al. (2014) Abnormalities in cortical bone, trabecular plates, and stiffness in postmenopausal women treated with glucocorticoids. J Clin Endocrinol Metab 99:4231-40|
|Stein, Emily M; Kepley, Anna; Walker, Marcella et al. (2014) Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning. J Bone Miner Res 29:1101-9|
|Stein, Emily M; Silverberg, Shonni J (2014) Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diabetes Endocrinol 2:165-74|
|Stein, Emily M; Silva, Barbara C; Boutroy, Stephanie et al. (2013) Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women. J Bone Miner Res 28:1029-40|
|Liu, X Sherry; Wang, Ji; Zhou, Bin et al. (2013) Fast trabecular bone strength predictions of HR-pQCT and individual trabeculae segmentation-based plate and rod finite element model discriminate postmenopausal vertebral fractures. J Bone Miner Res 28:1666-78|
|Cohen, Adi; Stein, Emily M; Recker, Robert R et al. (2013) Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study. J Clin Endocrinol Metab 98:1971-81|
|Liu, X Sherry; Stein, Emily M; Zhou, Bin et al. (2012) Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res 27:263-72|
|Stein, Emily M; Ortiz, Dionisio; Jin, Zhezhen et al. (2011) Prevention of fractures after solid organ transplantation: a meta-analysis. J Clin Endocrinol Metab 96:3457-65|
|Stein, Emily M; Liu, X Sherry; Nickolas, Thomas L et al. (2011) Abnormal microarchitecture and stiffness in postmenopausal women with ankle fractures. J Clin Endocrinol Metab 96:2041-8|