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Bone Mineral and Collagen Quality in Iliac Crest Biopsies of Patients Given Teriparatide: New Results from the Fracture Prevention Trial

Mineralized Tissue Section (E.P.P.), Research Division, The Hospital for Special Surgery, New York, New York 10021; and Eli Lilly and Co. (E.V.G., D.W.D., E.F.E.), Indianapolis, Indiana 46285

Address all correspondence and requests for reprints to: Dr. Emmett Glass, Eli Lilly and Co., Lilly Corporate Center, Drop code 6134, Indianapolis, Indiana 46285. E-mail: glassem{at}lilly.com.

Context: Evidence suggests that both bone mineral density and bone quality should be taken into account when assessing bone strength and fracture risk. Bone quality is a multifactor entity, of which bone architecture and material properties are two important components. Matrix mineralization, hydroxyapatite characteristics, and collagen cross-link ratio are key determinants of material properties. Fourier transform infrared imaging (FTIRI) yields data on these characteristics from bone sections.

Objective: We sought to determine collagen cross-link ratios and matrix mineralization of bone from patients randomized to teriparatide [recombinant human PTH (1–34)] treatment using FTIRI.

Design: The Fracture Prevention Trial was randomized, double blind, and placebo-controlled.

Setting: The trial was conducted at global clinical research centers.

Patients: Patients consisted of postmenopausal women with osteoporosis.

Interventions: Patients were randomized to receive daily sc injections of placebo (n = 12) or 20 µg (n = 13) or 40 µg (n = 13) teriparatide. Biopsies were obtained after 12 months of treatment or at the end of treatment (range, 19–24 months for end of treatment paired biopsies).

Main Outcome Measures: Biopsies were analyzed by FTIRI to determine the matrix mineralization (mineral to matrix), mineral crystallinity, and collagen cross-link ratio (pyridinoline/dehydrodihydroxylysinonorleucine) with a spatial resolution of approximately 6.3 µm.

Results: Patients administered teriparatide 20 and 40 µg/d exhibited significantly lower matrix mineralization, mineral crystallinity, and collagen cross-link ratio when compared with placebo.

Conclusions: These findings indicate that the bone-forming effect of teriparatide results in bone with a molecular profile reminiscent of younger bone.

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				S. Boonen, F. Marin, B. Obermayer-Pietsch, M. E. Simoes, C. Barker, E. V. Glass, P. Hadji, G. Lyritis, H. Oertel, T. Nickelsen, et al. Effects of Previous Antiresorptive Therapy on the Bone Mineral Density Response to Two Years of Teriparatide Treatment in Postmenopausal Women with Osteoporosis J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 852 - 860. [Abstract] [Full Text] [PDF]