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

• Published in: The journal of clinical endocrinology and metabolism 2005-08, Vol.90 (8), p.4644-4649
• Main Authors: Paschalis, Eleftherios P., Glass, Emmett V., Donley, David W., Eriksen, Erik F.
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biopsy; Bone Density - drug effects; Calcification, Physiologic - drug effects; Collagen - metabolism; Cross-Linking Reagents - metabolism; Endocrinopathies; Female; Fractures, Bone - metabolism; Fractures, Bone - pathology; Fractures, Bone - prevention & control; Fundamental and applied biological sciences. Psychology; Humans; Ilium - metabolism; Ilium - pathology; Medical sciences; Middle Aged; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - metabolism; Osteoporosis, Postmenopausal - pathology; Teriparatide - administration & dosage; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-2489

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.