Analysis of the effects of spaceflight and local administration of thrombopoietin to a femoral defect injury on distal skeletal sites

Ariane Zamarioli,Joao P B Ximenez,Nabarun Chakraborty,Kevin A Maupin,Melissa A Kacena,Aarti Gautam,Rasha Hammamieh,Paul J Childress,Gremah Adam,Zachery R Campbell

doi:10.1038/s41526-021-00140-0

Abstract

With increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space (“Flight”) and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.

Highlights

The emergence of commercialized space companies, NASA’s Artemis Program and Space Launch System, and continued development of additional national space programs are driving human spaceflight to greater horizons[1,2,3,4,5]
For each bone, we report significant (p < 0.05) and trending data (p < 0.09) for comparisons between groups in the same Habitat (i.e. saline as a vehicle control (Saline) + Earth versus TPO + Earth or Saline + Flight versus TPO + Flight) to understand the effects of treatment both on Earth and in flight as well as comparisons between spaceflight and Earth to assess the influence of gravity on the treatment (i.e. TPO + Earth versus TPO + Flight or Saline + Earth versus Saline + Flight)
In the sections below, for each bone examined, we present the results in the following order

Summary

Introduction

The emergence of commercialized space companies, NASA’s Artemis Program and Space Launch System, and continued development of additional national space programs are driving human spaceflight to greater horizons[1,2,3,4,5]. Missions planned to planetary bodies such as the Moon and Mars are in early stages with the intent of launching in the coming decades. These missions seek to establish more permanent human habitation on orbital stations and potential planetary colonies, which will require a surge of human participation[6]. The year-long study of twin astronauts Mark and Scott Kelly demonstrated long-duration spaceflight has effects ranging from ocular disturbances, significant radiation exposure resulting in epigenetic changes, and changes in muscle and bone[7]. Another study demonstrated that exposure to the microgravity environment of space resulted in losses in the spine, femoral neck, trochanter, and pelvis of about 1–1.6%, with considerable variation between individuals[9]. As BMD is lost, structural integrity is compromised leading to increased potential of fracture

Methods

Results

Conclusion