title: PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.
abstract: Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1707-1715, 2017.
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bartlow
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Oest
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Mann
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Zimmerman
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Bilal B
authors.initials: BB
authors.lastname: Butt
authors.affiliation: Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Damron
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D005269:Femur / Q000187:drug effects*; D006128:Growth / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010281:Parathyroid Hormone; D000077211:Zoledronic Acid
keywords: bone strength; juvenile mice; parathyroid hormone (PTH); zoledronic acid