Stephanie Sutter1, Kyle K Nishiyama, Anna Kepley, Bin Zhou, Ji Wang, Donald J McMahon, X Edward Guo, Emily M Stein. 1. Department of Medicine (S.S., K.K.N., A.K., D.J.M., E.M.S.), Columbia University College of Physicians and Surgeons, New York, New York 10032; and Bone Bioengineering Laboratory (B.Z., J.W., X.E.G.), Department of Biomedical Engineering, Columbia University, New York, New York 10027.
Abstract
CONTEXT: The mechanisms by which glucocorticoids (GCs) increase skeletal fragility are not well understood. OBJECTIVE: The objective of the study was to evaluate the microarchitecture, trabecular morphology, and biomechanical properties of bone in postmenopausal women treated with GCs. DESIGN: This was a case-control study. SETTING: The study was conducted at a university hospital outpatient facility. PATIENTS: Postmenopausal women treated with oral GCs for longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated in the study. MAIN OUTCOME MEASURES: Areal bone mineral density aBMD (BMD) by dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia were also measured. Whole-bone stiffness was estimated by finite element analysis. A novel technique, individual trabecula segmentation, was used to evaluate trabecular type (as plate or rod), orientation, and connectivity. RESULTS: DXA T-scores did not differ significantly at any site. GC subjects had significantly lower total, cortical, and trabecular vBMD and thinner cortices, fewer, thinner, more widely, and irregularly spaced trabeculae. They had fewer trabecular plates, fewer axially aligned trabeculae, and lower trabecular connectivity. Differences ranged from 4% to 65% for these trabecular measures and 5% to 17% for the cortical measures. Whole-bone stiffness was significantly lower (11%-16%) in GC subjects. Markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and resorption (C-telopeptide) were lower in the GC subjects. CONCLUSIONS: Despite similar areal BMD by DXA, GC-treated women had abnormal cortical and trabecular vBMD and microarchitecture at both the radius and tibia, including fewer trabecular plates, a less axially aligned trabecular network, lower trabecular connectivity, thinner cortices, and lower whole-bone stiffness. Further research into these abnormalities as mechanisms for fracture in GC-treated women is warranted.
CONTEXT: The mechanisms by which glucocorticoids (GCs) increase skeletal fragility are not well understood. OBJECTIVE: The objective of the study was to evaluate the microarchitecture, trabecular morphology, and biomechanical properties of bone in postmenopausal women treated with GCs. DESIGN: This was a case-control study. SETTING: The study was conducted at a university hospital outpatient facility. PATIENTS: Postmenopausal women treated with oral GCs for longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated in the study. MAIN OUTCOME MEASURES: Areal bone mineral density aBMD (BMD) by dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia were also measured. Whole-bone stiffness was estimated by finite element analysis. A novel technique, individual trabecula segmentation, was used to evaluate trabecular type (as plate or rod), orientation, and connectivity. RESULTS: DXA T-scores did not differ significantly at any site. GC subjects had significantly lower total, cortical, and trabecular vBMD and thinner cortices, fewer, thinner, more widely, and irregularly spaced trabeculae. They had fewer trabecular plates, fewer axially aligned trabeculae, and lower trabecular connectivity. Differences ranged from 4% to 65% for these trabecular measures and 5% to 17% for the cortical measures. Whole-bone stiffness was significantly lower (11%-16%) in GC subjects. Markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and resorption (C-telopeptide) were lower in the GC subjects. CONCLUSIONS: Despite similar areal BMD by DXA, GC-treated women had abnormal cortical and trabecular vBMD and microarchitecture at both the radius and tibia, including fewer trabecular plates, a less axially aligned trabecular network, lower trabecular connectivity, thinner cortices, and lower whole-bone stiffness. Further research into these abnormalities as mechanisms for fracture in GC-treated women is warranted.
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