title: μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.
abstract: Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: chantald@seas.upenn.edu.
authors.forename: Chantal M J
authors.initials: CM
authors.lastname: de Bakker
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: alaltman@mail.med.upenn.edu.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Altman
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: weits@mail.med.upenn.edu.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Tseng
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mtribble@seas.upenn.edu.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tribble
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: connie1@seas.upenn.edu.
authors.forename: Connie
authors.initials: C
authors.lastname: Li
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: abhic@mail.med.upenn.edu.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chandra
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: qinling@mail.med.upenn.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: xiaoweil@mail.med.upenn.edu.
authors.forename: X Sherry
authors.initials: XS
authors.lastname: Liu
mesh_terms: D019386:Alendronate / Q000008:administration & dosage* / Q000627:therapeutic use*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption; D001842:Bone and Bones / Q000473:pathology*; D004359:Drug Therapy, Combination; D021621:Imaging, Three-Dimensional; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D019386:Alendronate
keywords: Animal models/rodent; Anti-resorptive treatment; Bone stiffness; In vivo μCT; Parathyroid hormone; Trabecular bone microstructure