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

Abstract

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 microg (n = 13) or 40 microg (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 microm. RESULTS: Patients administered teriparatide 20 and 40 microg/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.