Monitoring Teriparatide-Associated Changes in Vertebral Microstructure by High-Resolution CT In Vivo: Results From the EUROFORS Study

Abstract

We introduce a method for microstructural analysis of vertebral trabecular bone in vivo based on HRCT. When applied to monitor teriparatide treatment, changes in structural variables exceeded and were partially independent of changes in volumetric BMD. Monitoring of osteoporosis therapy based solely on bone densitometry is insufficient to assess anti-fracture efficacy. Assessing bone microstructure in vivo is therefore of importance. We studied whether it is possible to monitor effects of teriparatide on vertebral trabecular microstructure independent of BMD by high-resolution CT (HRCT). In a subset of 65 postmenopausal women with established osteoporosis who participated in the EUROFORS study, HRCT scans of T(12), quantitative CT of L(1)-L(3), and DXA of L(1)-L(4) were performed after 0, 6, and 12 mo of teriparatide treatment (20 microg/d). We compared BMD and 3D microstructural variables in three groups of women, based on prior antiresorptive treatment: treatment-naïve; pretreated; and pretreated women showing inadequate response to treatment. We found statistically highly significant increases in most microstructural variables and BMD 6 mo after starting teriparatide. After 12 mo, apparent bone volume fraction (app. BV/TV) increased by 30.6 +/- 4.4% (SE), and apparent trabecular number (app. Tb.N.) increased by 19.0 +/- 3.2% compared with 6.4 +/- 0.7% for areal and 19.3 +/- 2.6% for volumetric BMD. The structural changes were partially independent of BMD as shown by a significantly larger standardized increase and a standardized long-term precision at least as good as DXA. Patients who had shown inadequate response to prior osteoporosis treatment did show improvements in BMD and structural measures comparable to treatment-naïve patients. HRCT is a feasible method for longitudinal microstructural analysis of human vertebrae in vivo, offers information beyond BMD, and is sufficiently precise to show profound effects of teriparatide after 12 mo.