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.Introduction: 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). Materials and Methods: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 g/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. Results: 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. Conclusions: 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.

Multi-level patient-specific modelling of the proximal femur. A promising tool to quantify the effect of osteoporosis treatment

“…However, the value of BMD measurements at a single time point is limited, because it has been shown that bone density explains only 70 per cent of the variance in the mechanical properties of bone (Goulet et al 1994). This result is in line with the finding that several clinical trials, investigating the effect of antiresorptive drugs, have shown that BMD cannot predict bone fracture risk accurately Graeff et al 2007). Furthermore, the difference between two consecutive BMD measurements provides only poor indications of changes in femoral strength due to osteoporosis treatment.…”

Differing effects of PTH 1–34, PTH 1–84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: An 18-month open-labeled observational study using HR-pQCT

“…First, a fraction of participants in each treatment group had received prior bisphosphonate treatment, which has been observed to blunt the response to anabolic therapy in the spine and hip. (40,41) There was no consistent pattern to suggest a blunting of the response in BTM, DXA, or HR-pQCT parameters in the case of previous bisphosphonate use in those treated with PTH 1-34 and PTH 1-84 (data not shown). Because the fraction of previous bisphosphonate users in those treated with PTH 1-34 (28%) was (nonsignificantly) lower compared with PTH 1-84 (45%), we cannot, however, exclude that this difference has impacted findings.…”

Short-term bone marker responses to teriparatide and strontium ranelate in patients with osteoporosis previously treated with bisphosphonates

“…The EUROFORS study showed that the use of teriparatide was associated with a significant improvement in the structural variables, obtained by high resolution CT, and bone mineral density in patients with an inadequate response to previous antiresorptive treatment, including bisphosphonates (23).…”