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

Abstract

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. 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. The Fracture Prevention Trial was randomized, double blind, and placebo-controlled. The trial was conducted at global clinical research centers. Patients consisted of postmenopausal women with osteoporosis. 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). 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. Patients administered teriparatide 20 and 40 microg/d exhibited significantly lower matrix mineralization, mineral crystallinity, and collagen cross-link ratio when compared with placebo. These findings indicate that the bone-forming effect of teriparatide results in bone with a molecular profile reminiscent of younger bone.