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 four weeks were given PTH(1–34) or vehicle (control) daily for eight weeks, or four 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 vs. 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.

Orchestrated delivery of PTH [1–34] followed by zoledronic acid prevents radiotherapy‐induced bone loss but does not abrogate marrow damage

“…A preload (1 N) was applied to each bone before loading to failure at 1 mm/min (Q‐Test; MTS). Bending strength was the primary outcome measure 15,26 …”

“…Significance was set at p ≤ 0.05. Sample size was determined for morphology and biomechanics outcomes based on prior work from our group7,14,15,17,26,30 and for flow cytometry study from the literature 31,32.…”