Immobilized animal model. Bilateral hind limbs of 8-week-old male SPF Wistar rats are fixed with the knee in a fully extended position using plaster casts.

Immobilized animal model. Bilateral hind limbs of 8-week-old male SPF Wistar rats are fixed with the knee in a fully extended position using plaster casts.

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Purpose Immobilization osteopenia is a major healthcare problem in clinical and social medicine. However, the mechanisms underlying this bone pathology caused by immobilization under load-bearing conditions are not yet fully understood. This study aimed to evaluate sequential changes to the three-dimensional microstructure of bone in load-bearing i...

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... were anesthetized by intraperitoneal injection with sodium pentobarbital (40 mg/kg), then bilateral hind limbs of rats in the Im group were fixed with the knee fully extended and the ankle in 40-45˚of45˚of plantar flexion using plaster casts (Plasrun 1 ; Alcare Co., Tokyo, Japan). The plaster cast was fitted from 1 cm below the hip joint to the distal foot and was changed every other day to prevent loosening with progression of muscle atrophy (Fig 1). Observations for skin abrasions and vein occlusions were performed at every cast rewinding. ...

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... However, bed rest and cast fixation limit the amount of mechanical stress applied to bone, which can cause immobilization-induced bone atrophy. Loss of bone density and degenerative changes in the bone microstructure occur in immobilization-induced bone atrophy; these lesions are caused by pathological changes in the cortical and cancellous bone 3 . ...
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Objectives This study aimed to determine whether mechanical stress via muscle contractile exercise with belt electrode-skeletal muscle electrical stimulation (B-SES) device effectively prevents immobilization-induced bone atrophy. Methods Wistar rats were randomly divided into the control (CON) group, immobilization (IM) group (immobilized treatment only), HES and LES groups (immobilized treatment and high or low-intensity electrical muscular stimulation through B-SES device). Bilateral femurs were used for X-ray micro-CT and biomechanical tests. Results The maximum load value was significantly lower in the IM and HES groups than in the CON group and significantly higher in the LES group than in the IM group. The maximum crushing load was significantly lower in the IM, HES, and LES groups than in the CON group, and significantly higher in the HES and LES groups than that in the IM group. In micro-CT, the mechanical stress by B-SES device did not affect degenerative microstructural changes in the cortical bone, but prevented those changes in the cancellous bone. Conclusions Applying mechanical stress via B-SES device suppressed the loss of cancellous bone density and degenerative microstructural changes caused by immobilization, which in turn suppressed the reduction of bone strength. From these findings, muscle contractile exercise may be effective in preventing immobilization-induced bone atrophy.
... In conditions such as bed rest and spinal cord injury, bone loss is rapid and acute, ranging from 5% to 25%, depending on the skeletal sites and injury severity [48]. Rodent models representing these clinically mechanically unloaded or muscle disuse conditions, including tail suspension, cast immobilization, intramuscular botox injections, and tendon resection, exhibit bone loss, which might potentially jeopardize bone regeneration [49][50][51][52]. ...
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Reduced skeletal loading associated with many conditions, such as neuromuscular injuries, can lead to bone fragility and may threaten the success of implant therapy. Our group has developed a botulinum toxin A (botox) injection model to imitate disease-reduced skeletal loading and reported that botox dramatically impaired the bone formation and osseointegration of titanium implants. Semaphorin 3A (sema3A) is an osteoprotective factor that increases bone formation and inhibits bone resorption, indicating its potential therapeutic role in improving osseointegration in vivo. We first evaluated the sema3A effect on whole bone morphology following botox injections by delivering sema3A via injection. We then evaluated the sema3A effect on the osseointegration of titanium implants with two different surface topographies by delivering sema3A to cortical bone defect sites prepared for implant insertion and above the implants after insertion using a copper-free click hydrogel that polymerizes rapidly in situ. Implants had hydrophobic smooth surfaces (PT) or multiscale biomimetic micro/nano topography (SLAnano). Sema3A rescued the botox-impaired bone formation. Furthermore, biomimetic Ti implants improved the bone-to-implant contact (BIC) and mechanical properties of the integrated bone in the botox-treated rats, which sema3A enhanced. This study demonstrated the value of biomimetic approaches combining multiscale topography and biologics in improving the clinical outcomes of implant therapy.
... Зміни мікроархітектури кістки в умовах іммобілізації мають двофазний перебіг: на першому етапі виникає посилена трабекулярна перфорація, згодом збільшується товщина трабекул, при цьому міцність кістки зберігається. У подальшому кісткова маса та якість кістки різко знижуються й підвищується ризик перелому [1,[14][15][16]. ...
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Background. Disuse (рost-immobilization) osteoporosis is defined as secondary loss of bone mass in case of the absence or insufficient mechanical load on the skeleton. This di­sease can be associated with various risk factors, including long-time bed rest. The purpose of the research was to analyze modern lite­rary data on the mechanisms of development, principles of diagnosis and treatment of disuse osteoporosis and to present own clinical data of disuse osteoporosis in the patients with multiple injuries of the skeleton in the conditions of war in Ukraine. Materials and methods. The review was based on the analysis of literature sources from the PubMed, WOS, Scopus, Google, Google Scholar, Cochrane Library databases for the years 2007–2022. The search was conducted using keywords: disuse osteoporosis, immobilization, bed rest, bone mineral density (BMD), bone remode­ling, regene­ration. Results. The data on the theory of the mechanostat are considered as links in the appearance of disuse osteoporosis. In conditions of immobilization, bone remodeling processes are slowing down. Histomorphometric studies confirm a decrease in trabecular bone density, thickness of the cortical layer, and an increase in its porosity. A change in bone architecture with a biphasic course is observed. Disruption of the synchronicity of remodeling processes with a decrease in the rate of osteoblastoge­nesis and an increase in osteoclastogenesis was noted, and the role of osteocytes as mechanosensors was emphasized. Disuse osteoporosis leads to a violation of biochemical marker of bone meta­bolism. Early laboratory manifestations of bed rest were recorded in the form of a violation of calcium level, an increase in bone resorption markers, while bone formation markers did not change significantly. Bone loss in disuse osteoporosis is manifested by a decrease in BMD indices. The greatest decrease was recorded in the lower extremities’ bones and the vertebrae of the lumbar spine. Modern methods of treatment of disuse osteoporosis involve the use of antiresorptive and osteoanabolic agents but clinical data are limited, which requires multicenter randomized studies. The article presents 3 clinical examples of disuse osteoporosis after gunshot fractures of the lower extremities’ bones.