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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK084337-03
Application #
8129509
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-08-10
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
3
Fiscal Year
2011
Total Cost
$149,776
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Liu, Y; Dimango, E; Bucovsky, M et al. (2018) Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids. Osteoporos Int 29:2121-2127
Carrelli, Angela; Bucovsky, Mariana; Horst, Ronald et al. (2017) Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women. J Bone Miner Res 32:237-242
Sutter, Stephanie A; Stein, Emily M (2016) The Skeletal Effects of Inhaled Glucocorticoids. Curr Osteoporos Rep 14:106-13
Wang, Ji; Stein, Emily M; Zhou, Bin et al. (2016) Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures. Bone 88:39-46
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
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
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
Nickolas, Thomas L; Stein, Emily M; Dworakowski, Elzbieta et al. (2013) Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res 28:1811-20
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

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