Iliac crest biopsies were obtained from postmenopausal osteoporotic women enrolled in the TOP Study after 18 months of daily sc injections of placebo or 100 μg parathyroid hormone 1-84 (PTH). All subjects received daily treatment with calcium (700 mg) and vitamin D (400 IU). There were no significant differences between groups in age, weight, bone turnover markers, or spine and hip bone mineral density at baseline. Recently we reported (ASBMR, 2004) results of quantitative histomorphometry in these biopsies. Relative to placebo-treated subjects, cancellous bone volume (Cn.BV/TV), was 48% higher in subjects treated with PTH. This increase could be accounted for by increases in trabecular number (Tb.N) (24%) and thickness (Tb.Th) (17%) which resulted in a 21% decrease in trabecular separation (Tb.Sp). Prior to sectioning for histomorphometry, the biopsies (n = 8/group) were subjected to micro-computed tomography (Micro-CT 20, Scanco Medical, AG). The biopsies were scanned at a voxel size of 17 μm. Trabecular bone was segmented from the marrow or soft tissue using a threshold of 25.5% of the maximal gray scale value. Trabecular structures were quantified using 3-D morphometric analysis.
The values for trabecular structure obtained by μCT were very similar to those obtained by histomorphometry. Compared with placebo-treated subjects, mean Cn.BV/TV was 45% higher in PTH-treated subjects (PTH = 23.3% ± 2.0, placebo = 16.1% ± 1.4; P = 0.036). The higher Cn.BV/TV was the result of 12% and 17% increases, in mean Tb.N (PTH = 1.40/mm ± 0.06, placebo = 1.25/mm ± 0.04; P = 0.093) and mean Tb.Th (PTH = 186 μm ± 12, placebo = 159 μm ± 11; P = 0.128), respectively, with a 10% lower mean Tb.Sp (PTH = 696 μm ± 27, placebo = 771 μm ± 23; P = 0.036). Importantly, mean connectivity density (Conn.D) was 22% higher (PTH = 4.81/mm3 ± 0.34, placebo = 3.93/mm3 ± 0.52; P = 0.074). The mean structure model index (SMI) was also significantly lower (55%) in PTH-treated subjects relative to placebo-treated subjects (0.49 ± 0.25 vs 1.09 ± 0.16, respectively; P = 0.046), indicating a better connected trabecular architecture with a more plate-like structure, both indicative of a stronger bone.
In conclusion, relative to placebo, treatment of osteoporotic women for 18 months with PTH resulted in marked increases in Cn.BV/TV, improved trabecular connectivity and a more plate-like structure. Structural variables obtained by μCT and bone histomorphometry were remarkably similar. All of these results are consistent with an increase in bone strength and the marked reduction in vertebral fracture incidence observed in the TOP Study.
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Faculty Member's Name: DW Dempster, PhD
Consultant: NPS
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