Award Title: Unsolved Issues for the Skeleton and role of FGF23-Klotho axis; Contribution of a Bone Digital Twin [Bone On ISS
Funder: UK Space Agency

Abstract: Prediction of fracture risk relies on measures of gross bone mass, but bone strength is also determined by bone size,
shape, and material properties. This study will investigate the effect of space flight on the material properties of bone using
a novel reference point indentation method in the human tibia. Reference point indentation is a novel, minimally invasive,
method of measuring bone material properties in vivo at the tissue level by testing the resistance of the outer cortex of the
tibia to penetration. A small needle is placed on the bone surface and a micro-indentation (<0.3 mm depth) is made in the
cortex in response to a fixed level of force (40 N). By producing a small fracture, the properties of the collagen matrix
(alongside other material characteristics) can be tested. Reference point indentation distinguishes between osteoporotic
fracture cases and stress fracture cases compared with controls, and is sensitive to changes in bone strength with drug
treatments and exercise, even in the absence of changes with state-of-the-art imaging. State-of-the art imaging techniques
of weight-bearing and non-weight-bearing bone and analyses of novel blood and urine markers will help us to better
characterise the bone response to spaceflight. Measurements will be taken before and serially for up to 2 years after
spaceflight on the International Space Station. The aim of this approach is to improve monitoring of skeletal health in
response to, and recovery from, space flight. This trial is a collaborative trial and is sponsored by the Europen Space
Agency (ESA), the Italian Space Agency (ASI), the German Space Agency (DLR), and the French Space Agency (CNES)
and approved to start by ESA on astronauts on-board the International Space Station

Lay Abstract: Prediction of fracture risk relies on measures of gross bone mass, but bone strength is also determined by bone size,
shape, and material properties. This study will investigate the effect of space flight on the material properties of bone using
a novel reference point indentation method in the human tibia. Reference point indentation is a novel, minimally invasive,
method of measuring bone material properties in vivo at the tissue level by testing the resistance of the outer cortex of the
tibia to penetration. A small needle is placed on the bone surface and a micro-indentation (<0.3 mm depth) is made in the
cortex in response to a fixed level of force (40 N). By producing a small fracture, the properties of the collagen matrix
(alongside other material characteristics) can be tested. Reference point indentation distinguishes between osteoporotic
fracture cases and stress fracture cases compared with controls, and is sensitive to changes in bone strength with drug
treatments and exercise, even in the absence of changes with state-of-the-art imaging. State-of-the art imaging techniques
of weight-bearing and non-weight-bearing bone and analyses of novel blood and urine markers will help us to better
characterise the bone response to spaceflight. Measurements will be taken before and serially for up to 2 years after
spaceflight on the International Space Station. The aim of this approach is to improve monitoring of skeletal health in
response to, and recovery from, space flight. This trial is a collaborative trial and is sponsored by the Europen Space
Agency (ESA), the Italian Space Agency (ASI), the German Space Agency (DLR), and the French Space Agency (CNES)
and approved to start by ESA on astronauts on-board the International Space Station

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: MUSCULOSKELETAL