Developing an exercise intervention to minimise hip bone mineral density loss following traumatic lower limb amputation: a Delphi study.

Objective: To elicit expert opinion and gain consensus on specific exercise intervention parameters to minimise hip bone mineral density (BMD) loss following traumatic lower limb amputation.

Methods: In three Delphi rounds, statements were presented to a panel of 13 experts from six countries. Experts were identified through publications or clinical expertise.

OPN, BSP, and Bone Quality-Structural, Biochemical, and Biomechanical Assessment in OPN, BSP, and DKO Mice.

Osteopontin (OPN) and Bone Sialoprotein (BSP), abundantly expressed by osteoblasts and osteoclasts, appear to have important, partly overlapping functions in bone. In gene-knockout (KO, -/-) models of either protein and their double (D)KO in the same CD1/129 genetic background, we analyzed the morphology, matrix characteristics, and biomechanical properties of femur bone in 2 and 4 month old, male and female mice. OPN mice display inconsistent, perhaps localized hypermineralization, while the BSP are hypomineralized throughout ages and sexes, and the low mineralization of young DKO mice recovers with age.

Dietary supplementation with nacre reduces cortical bone loss in aged female mice.

Aging is associated with detrimental bone loss leading to fragility fractures in both men and women. Notably, a majority of bone loss with aging is cortical, as well as a large number of fractures are non-vertebral and at the non-hip sites. Nacre is a product of mollusks composed of calcium carbonate embedded in organic components.

Adequacy of in-mission training to treat tibial shaft fractures in mars analogue testing.

Long bone fractures are a concern in long-duration exploration missions (LDEM) where crew autonomy will exceed the current Low Earth Orbit paradigm. Current crew selection assumptions require extensive complete training and competency testing prior to flight for off-nominal situations. Analogue astronauts (n = 6) can be quickly trained to address a single fracture pattern and then competently perform the repair procedure.

Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation.

Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974).

Effects of Posture and Walking on Tibial Vascular Hemodynamics Before and After 14 Days of Head-Down Bed Rest.

Human skeletal hemodynamics remain understudied. Neither assessments in weight-bearing bones during walking nor following periods of immobility exist, despite knowledge of altered nutrient-artery characteristics after short-duration unloading in rodents. We studied 12 older adults (8 females, aged 59 ± 3 years) who participated in ambulatory near-infrared spectroscopy (NIRS) assessments of tibial hemodynamics before (PRE) and after (POST) 14 days of head-down bed rest (HDBR), with most performing daily resistance and aerobic exercise countermeasures during HDBR.

Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice.

Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders.

Musculoskeletal research in human space flight - unmet needs for the success of crewed deep space exploration.

Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper "Human Physiology - Musculoskeletal system", this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight.

Imaging of the human cochlea using micro-computed tomography before and after cochlear implantation: comparison with cone-beam computed tomography.

Purpose: Analysis of cochlear structures and postoperative temporal bone (TB) imaging are gaining importance in the evaluation of cochlear implantation (CI°). Our aims were to explore the microarchitecture of human cochlea using micro-computed tomography (μCT), analyze electrode's placement inside cochlea after CI°, and compare pre-/post-implantation μCT scans with cone-beam CT (CBCT) scans of same TBs.

Methods: Cadaveric TBs were scanned using μCT and CBCT then underwent CI° using straight electrodes.

Hindlimb unloading in C57BL/6J mice induces bone loss at thermoneutrality without change in osteocyte and lacuno-canalicular network.

Impaired mechanical stimuli during hindlimb unloading (HLU) are believed to exacerbate osteocyte paracrine regulation of osteoclasts. We hypothesized that bone loss and deterioration of the osteocyte lacuno-canalicular network are attenuated in HLU mice housed at thermoneutrality (28 °C) compared with those housed at ambient temperature (22 °C). Following acclimatization, 20-week-old male C57BL/6J mice were submitted to HLU or kept in pair-fed control cages (CONT), for 5 days (5d) or 14d, at 22 °C or 28 °C.

Preclinical safety study of nacre powder in an intraosseous sheep model.

Objectives: The purpose of this preclinical study was to evaluate the safety, the local tissue effects and bone healing performance (osteoconduction, osseointegration) of nacre powder in a sheep intraosseous implantation model. This represents the first preclinical study to assess nacre safety and efficacy in supporting new bone formation in accordance with the ISO 10993 standard for biomedical devices.

Methods: The local tissue effects and the material performance were evaluated 8 weeks after implantation by qualitative macroscopic observation and qualitative as well as semiquantitative microscopic analyses of the bone sites.

The effects of combined amplitude and high-frequency vibration on physically inactive osteopenic postmenopausal women.

To evaluate whole-body vibration (WBV) osteogenic potential in physically inactive postmenopausal women using high-frequency and combined amplitude stimuli. Two-hundred fifty-five physically inactive postmenopausal women (55-75 years) with 10-year major osteoporotic fracture risk (3%-35%) participated in this 18-month study. For the first 12 months, the vibration group experienced progressive 20-min WBV sessions (up to 3 sessions/week) with rest periods (30-60 s) between exercises.

Protective Effect on Bone of Nacre Supplementation in Ovariectomized Rats.

Nacre has emerged as a beneficial natural product for bone cells and tissues, but its effect was only studied by gavage in the ovariectomized mouse model. We sought to assess the antiosteoporotic effect of nacre through a nutritional supplementation in the ovariectomized rat model. Sixteen-week-old female Wistar rats were either Sham-operated or bilateral ovariectomized (OVX) and then fed with standard diet (Sham and OVX groups) or standard diet supplemented with either 0.

DI-5-Cuffs: Bone Remodelling and Associated Metabolism Markers in Humans After Five Days of Dry Immersion to Simulate Microgravity.

The dry immersion (DI) model closely reproduces factors of spaceflight environment such as supportlessness, mechanical and axial unloading, physical inactivity, and induces early increased bone resorption activity and metabolic responses as well as fluid centralization. The main goal of this experiment was to assess the efficacity of venoconstrictive thigh cuffs, as countermeasure to limit cephalad fluidshift, on DI-induced deconditioning, in particular for body fluids and related ophthalmological disorders. Our specific goal was to deepen our knowledge on the DI effects on the musculoskeletal events and to test whether intermittent counteracting fluid transfer would affect DI-induced bone modifications.

YAP Transcriptional Activity Dictates Cell Response to TNF .

YAP/TAZ are transcription co-factors recently described responsive to pro-inflammatory cytokines and involved in inflammatory-related disorders. However, the role of tumor necrosis factor (TNF), a major pro-inflammatory cytokine, on YAP signaling is not well understood and controversial. Here, we observe , using wild type and YAP knockout HEK293 cells, that TNF triggers YAP nuclear translocation and transcriptional activity, thus being dependent on Rho family of GTPases.

Dissociation of Bone Resorption and Formation in Spaceflight and Simulated Microgravity: Potential Role of Myokines and Osteokines?

The dissociation of bone formation and resorption is an important physiological process during spaceflight. It also occurs during local skeletal unloading or immobilization, such as in people with neuromuscular disorders or those who are on bed rest. Under these conditions, the physiological systems of the human body are perturbed down to the cellular level.

YAP/TAZ: Key Players for Rheumatoid Arthritis Severity by Driving Fibroblast Like Synoviocytes Phenotype and Fibro-Inflammatory Response.

Objective: The role of YAP/TAZ, two transcriptional co-activators involved in several cancers, was investigated in rheumatoid arthritis (RA).

Methods: Fibroblast like synoviocytes (FLS) from patients with RA or osteoarthritis were cultured in 2D or into 3D synovial organoids. Arthritis rat model (n=28) and colitis mouse model (n=21) were used.

Osteocytes and Weightlessness.

Purpose Of Review: Osteocytes are considered to be the cells responsible for mastering the remodeling process that follows the exposure to unloading conditions. Given the invasiveness of bone biopsies in humans, both rodents and in vitro culture systems are largely adopted as models for studies in space missions or in simulated microgravity conditions models on Earth.

Recent Findings: After a brief recall of the main changes in bone mass and osteoclastic and osteoblastic activities in space-related models, this review focuses on the potential role of osteocytes in directing these changes.

The Skeletal Cellular and Molecular Underpinning of the Murine Hindlimb Unloading Model.

Bone adaptation to spaceflight results in bone loss at weight bearing sites following the absence of the stimulus represented by ground force. The rodent hindlimb unloading model was designed to mimic the loss of mechanical loading experienced by astronauts in spaceflight to better understand the mechanisms causing this disuse-induced bone loss. The model has also been largely adopted to study disuse osteopenia and therefore to test drugs for its treatment.

Hypergravity as a gravitational therapy mitigates the effects of knee osteoarthritis on the musculoskeletal system in a murine model.

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g).

Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission.

Spaceflight-induced bone losses have been reliably reproduced in Hind-Limb-Unloading (HLU) rodent models. However, a considerable knowledge gap exists regarding the effects of low-dose radiation and microgravity together. Ten-week-old male C57BL/6J mice, randomly allocated to Control (CONT), Hind-Limb Unloading (HLU), and Hind-Limb Unloading plus Irradiation (HLUIR), were acclimatized at 28 °C, close to thermoneutral temperature, for 28 days prior to the 14-day HLU protocol.

Ultrafast Laser Processing of Nanostructured Patterns for the Control of Cell Adhesion and Migration on Titanium Alloy.

Femtosecond laser texturing is a promising surface functionalization technology to improve the integration and durability of dental and orthopedic implants. Four different surface topographies were obtained on titanium-6aluminum-4vanadium plates by varying laser processing parameters and strategies: surfaces presenting nanostructures such as laser-induced periodic surface structures (LIPSS) and 'spikes', associated or not with more complex multiscale geometries combining micro-pits, nanostructures and stretches of polished areas. After sterilization by heat treatment, LIPSS and spikes were characterized to be highly hydrophobic, whereas the original polished surfaces remained hydrophilic.

Effects of centrifugation and whole-body vibrations on blood-brain barrier permeability in mice.

Modifications of gravity levels induce generalized adaptation of mammalian physiology, including vascular, brain, muscle, bone and immunity functions. As a crucial interface between the vascular system and the brain, the blood-brain barrier (BBB) acts as a filter to protect neurons from pathogens and inflammation. Here we compare the effects of several protocols of hypergravity induced by centrifugation and whole-body vibrations (WBV) on BBB integrity.

Laser-Based Hybrid Manufacturing of Endosseous Implants: Optimized Titanium Surfaces for Enhancing Osteogenic Differentiation of Human Mesenchymal Stem Cells.

Additive manufacturing (AM) is becoming increasingly important in the orthopedic and dental sectors thanks to two major advantages: the possibility of custom manufacturing and the integration of complex structures. However, at smaller scales, surface conditions of AM products are not mastered. Numerous non-fused powder particles give rise to roughness values (Sa) greater than 10 μm, thus limiting biomedical applications since the surface roughness of, e.