Reduced Bone Density Research Articles

Ochronotic arthropathy: skeletal manifestations and orthopaedic treatment

Alkaptonuria is an extremely rare disorder of tyrosine metabolism caused by an autosomal recessive enzymatic deficiency of homogentisic acid (HGA) oxidase, causing its accumulation in collagenous structures, especially in hyaline cartilage. It is characterized by a triad of homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and arthropathy of the spine and large weight-bearing joints. Several clinical manifestations were described including coronary and valvular calcification, aortic stenosis, limited chest expansion, and renal, urethral and prostate calculi as well as ocular and cutaneous pigmentation. Skeletal affection usually presents as spondylotic changes of the spine. The knee is the most common peripheral joint to be involved. Enthesopathy or tendon ruptures may occur, and reduced bone density is not unusual. A low-protein diet and ascorbic acid may reduce HGA levels. Nitisinone can safely and effectively reduce HGA production and urinary excretion. In severe ochronotic arthropathy, joint arthroplasty can offer reliable pain relief and excellent functional outcomes. Cementless fixation is successful in young patients.

Does pregnancy in adolescence increase the chances of osteoporosis among aged women? Findings from the ELSI study.

Bone mineral density changes during the life span, rising rapidly during adolescence, plateauing around 30 years of age and decreasing in later years. Life events such as pregnancy and lactation temporarily reduce bone density, and their long-term effects on osteoporosis development are still unclear. This study aimed to analyse the association between pregnancy in adolescence and osteoporosis in aged women. This was a cross-sectional study conducted with data from the ELSI-Brazil baseline (2015-2016). The sample consisted of 2634 women aged 60 years old or over with complete information for the variables of interest. Data collection was conducted through individual home interviews and physical assessments. The dependent variable was osteoporosis and the independent variable of interest was pregnancy in adolescents under 20 years of age. The association between the variables was tested using multiple logistic regression. The prevalence of osteoporosis was 32%, and the percentage of women who reported pregnancy in adolescence was 38%. After adjusting for socio-economic and health variables, an association was observed between pregnancy in adolescence and osteoporosis (OR = 1.38; 95% CI = 1.09-1.73), which indicates that specific bone health interventions for teenage mothers could help prevent osteoporosis later in life. Women who reported pregnancy before age 20 were more likely to report osteoporosis in old age, indicating that pregnancy in adolescence can be a criterion for directing actions to prevent osteoporosis in aged women.

Identifying Molecular Mechanisms of Cinnamomum cassia in the Treatment of Osteoporosis Based on Network Pharmacology and Validations

Background Osteoporosis is a common condition among the elderly, characterized by reduced bone density and an increased susceptibility to fractures. The efficacy of Cinnamomum cassia in treating osteoporosis is recognized, though its precise molecular mechanisms remain unclear. Purpose To investigate the molecular mechanisms underlying the therapeutic effects of C. cassia using network pharmacology, molecular docking technology (MDT), and molecular dynamics simulation (MDS). Materials and Methods Bioinformatics databases identified active compounds and disease targets. Protein-protein interaction (PPI) networks were constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. MDT and MDS validated the binding affinity between C. cassia’s active compounds and key targets. Results Ten active compounds of C. cassia were identified, modulating the PPAR, HIF-1, AMPK, and cAMP signaling pathways. Key genes include PPARG, PTGS2, PPARA, BDNF, and RXRA. Molecular docking and simulations confirmed high binding affinity between active compounds and targets, supporting their role in regulating bone metabolism. Conclusion This study highlights the multi-target mechanisms of C. cassia in treating osteoporosis, emphasizing its therapeutic potential through pathway-based modulation of key genes. These findings provide a basis for further research in modernizing traditional Chinese medicine for osteoporosis management.

Insights into skeletal involvement in adult Gaucher disease: a single-center experience.

Gaucher disease (GD) is a lysosomal storage disorder causing systemic and skeletal complications. This study evaluates bone health in adult GD type 1 patients, focusing on skeletal complications, bone mineral density (BMD), and biochemical markers. A cohort of adult GD type 1 patients followed up at Ege University Pediatric Metabolism Department were retrospectively examined. This study included 32 patients with GD type 1, comprising 11 males (34.4%) and 21 females (65.6%). The median age at diagnosis was 20.5years (min: 3-max:65), and at enrolment, it was 35years (min:18-max:71). Most patients (93.8%) had organomegaly, and 93.8% had cytopenia. Common genetic variants were p.Asn409Ser (60.9%), p.Leu483Pro (7.8%), and p.Asp448His(4.7%). All patients were on enzyme replacement therapy (ERT) for a median of 11years (min:2-max:18). Bone complications included pathologic fractures in six patients (19%) and avascular necrosis in 12 patients (37.5%). Bone pain was reported by 93.7% of patients at admission and persisted in 59.4% during follow-up. DXA scans showed abnormal bone mineral density (BMD) in 62.5% of patients initially, with a significantly low bone density in 3.1% and reduced bone density in 59.3%. BMD improved with treatment, as evidenced by a significant increase in Z scores (p < 0.05). Elevated chitotriosidase (75%), ferritin (50%), and immunoglobulin G (21.9%) levels were noted but did not correlate with BMD. Seven patients (22%) were splenectomized, all with bone issues. Bone health in GD involves multiple factors beyond biochemical markers. While ERT improves BMD, bone pain and fractures remain significant issues. Comprehensive management, including regular BMD monitoring and better vitamin D supplementation adherence, is crucial. Further research is needed to improve treatments for bone complications in GD.

Efficacy of GnRH antagonists in the treatment of uterine fibroids: a meta-analysis.

Uterine fibroids are the most common pelvic tumors in women, representing the primary indication of hysterectomy. Gonadotropin-releasing hormone (GnRH) antagonists represent a new therapeutic option for premenopausal women. The aim of this review is to evaluate the efficacy and safety of GnRH antagonists in the treatment of uterine fibroids (size reduction and symptom control). A review of studies from electronic databases (PubMed and Cochrane Central) published up to December 2023 was performed. Eleven randomized clinical trials with a total of 4164 patients were included in the review, which evaluated GnRH antagonists (Relugolix, Elagolix, Linzagolix and Cetrorelix) against placebo or GnRH agonists in premenopausal women with uterine fibroids and heavy menstrual bleeding. The results of the measures evaluated to determine the efficacy and safety of GnRH antagonists versus placebo are favorable for the variables of control of uterine bleeding (Relative risk (RR) = 5.09; 95% CI 3.19 to 8.14), percentage reduction of fibroid volume (Mean difference (MD) = -27.36; 95% CI -38.89 to -15.83) and lower reduction of bone density (MD -0.35; 95% CI -0.47 to -0.24). The results do not allow us to conclude whether there are differences between the alternatives compared in the control of vasomotor symptoms. GnRH antagonists represent an effective alternative for uterine fibroids treatment as they allow a superior reduction in menstrual bleeding and uterine fibroid volume compared to the placebo group.

Pym-18a, a novel pyrimidine derivative ameliorates glucocorticoid induced osteoblast apoptosis and promotes osteogenesis via autophagy and PINK 1/Parkin mediated mitophagy induction.

Glucocorticoid-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis, marked by reduced bone density and impaired osteoblast function. Current treatments have serious side effects, highlighting the need for new drug candidates. Pyrimidine derivatives have been noted for their potential in suppressing osteoclastogenesis, but their effects on osteogenesis and GIOP remain underexplored. Our recent study identified a novel pyrimidine derivative, Pym-18a, which enhances osteoblast functions. In this study, Pym-18a was found to mitigate the detrimental effects of Dexamethasone (Dex) in osteoblast cells and in GIOP in Balb/C mice. Pretreatment with Pym-18a followed by Dex (100 µM) for 24 h restored osteoblast alkaline phosphatase activity and viability. Pym-18a reduced Dex-induced apoptosis and reactive oxygen species (ROS) generation at cellular and mitochondrial levels and preserved mitochondrial membrane potential. Dex impaired autophagy and mitophagy, but Pym-18a pretreatment increased expression of autophagy markers (LC3II) and mitophagy markers (PINK1, Parkin, TOM20) while decreasing P62 expression. The osteogenic effects of Pym-18a were diminished in the presence of 3-MA (an autophagy inhibitor). In silico studies showed mTOR inhibition by Pym-18a, corroborated by its suppression of Dex-induced mTOR activation. In vivo, Pym-18a (10 mg/kg) significantly improved bone microarchitecture, trabecular connectivity, and strength, and corrected P1NP and CTX levels altered by Dex. Pym-18a also promoted autophagy, mitophagy, and suppressed mTOR activation in GIOP mice. Overall, Pym-18a mitigates detrimental effect of Dex by modulating autophagy and PINK/Parkin-mediated mitophagy through mTOR inhibition, suggesting it as a potential novel therapeutic option for GIOP.

Clinical Practice Guideline: The Diagnosis and Treatment of Osteoporosis.

Osteoporosis is a common disease that affects approximately 6 million people in Germany alone. Osteoporotic fractures impair the quality of life and may make independent living impossible. Recommendations on the diagnosis and treatment of osteoporosis are indispensable for the effective care of this large group of patients. For a thorough updating of the German clinical practice guideline (an evidence-based guideline with recommendations for clinical practice) on osteoporosis, a comprehensive, systematic search for relevant publications was carried out, including guidelines from other countries. The retrieved literature was assessed with standardized (Oxford) criteria, and clinically relevant key questions were answered according to the PICO scheme ("population, intervention, comparison, outcomes"). The assessment of clinical risk factors for osteoporosis is the basis of osteoporosis diagnostics, which should be carried out quickly after a fracture. If risk factors are present in a postmenopausal woman or a man aged 50 or above, bone densitometry testing with dual-energy x-ray absorptiometry (DXA) is recommended. The further diagnostic evaluation should proceed in stepwise fashion depending on the clinical symptoms, the fracture status, and the degree of bone density reduction. Pharmacotherapy should be adapted to the fracture risk. Osteoanabolic treatment is recommended with high priority if the patient is judged to have a very high risk of fracture (10% or more in the next three years). The further course and duration of treatment should be determined individually, depending on the evolution of the patient's clinical state. Prerequisites for the optimal treatment of patients with osteoporosis include a correct diagnosis and interdisciplinary and interprofessional collaboration to determine and provide the proper treatment. 71% of persons with osteoporosis in Germany are still untreated, and this gap must be closed.

Mechanisms of Ferroptosis in bone disease: A new target for osteoporosis treatment.

Osteoporosis (OP) is a common disease in the elderly, characterized by decreased bone strength, reduced bone density, and increased fracture risk. There are two clinical types of osteoporosis: primary osteoporosis and secondary osteoporosis. The most common form is postmenopausal osteoporosis, which is caused by decreased estrogen production after menopause. Secondary osteoporosis, on the other hand, occurs when certain medications, diabetes, or nutritional deficiencies lead to a decrease in bone density. Ferroptosis, a new iron-dependent programmed cell death process, is critical in regulating the development of osteoporosis, but the underlying molecular mechanisms are complex. In the pathologic process of osteoporosis, several studies have found that ferroptosis may occur in osteocytes, osteoblasts, and osteoclasts, cell types closely related to bone metabolism. The imbalance of iron homeostasis in osteoblasts and excessive iron accumulation can promote lipid peroxidation through the Fenton reaction, which induces ferroptosis in osteoblasts and affects their role in regulating bone metabolism. Ferroptosis in osteoblasts inhibits bone formation and reduces the amount of new bone production. Osteoclast-associated ferroptosis abnormalities, on the other hand, may alter the homeostasis of bone resorption. In this paper, we start from the molecular mechanism of ferroptosis, and introduce the ways in which ferroptosis affects the physiological and pathological processes of the body. After that, the effects of ferroptosis on osteoblasts and osteoclasts will be discussed separately to elucidate the molecular mechanism between ferroptosis and osteoporosis, which will provide a new breakthrough for the prevention and treatment of osteoporosis and a more effective and better idea for the treatment strategy of osteoporosis.

Bone mass distribution of 892 distal tibiae and implications for the treatment of medial malleolar fractures.

The medial malleolus is involved in up to 50 % of ankle fractures. When surgery is required, a thorough understanding of bone mass distribution within the distal tibia is crucial for selecting and positioning screws to ensure stable fixation. Despite its clinical significance, data on the bone mass distribution in the distal tibia remains limited. A total of 892 anonymized computed tomography data sets were analyzed to assess bone mass distribution in the distal tibia. Patients were categorized based on age, sex and stratified into those with normal (Hounsfield units (HU) ≥ 122) and reduced (HU < 122) bone density. Utilizing color-coded thermal maps, bone density and bone mass distribution in the distal tibia was visualized. Subsequently, simulation of potential screw trajectories for medial malleolar fracture treatment were conducted and bone density along those trajectories measured. Patients exhibiting reduced bone density (n = 442) were significantly older (69 (IQR 60-78)) than those with regular bone density (n = 450) aged (62 (IQR 47-72)) and more often female (p < 0.0001). The highest bone density was located within the proximal one centimeter from the distal tibial articular surface. Another region of dense bone was found at the transition from the distal tibia to the medial malleolus. Bone density was lowest at the distal tibial shaft region beginning at around 30 mm (in females) and 33 mm (in males) from the tip of the medial malleolus. Our data highlights the areas with the highest bone density in the distal tibia. When fixing medial malleolar fractures with unicortical partially threaded screws, this data suggests that screws with a length between 36 and 41 mm should be used at the anterior colliculus and intercollicular. However, regardless of our findings, fracture morphology must be considered, and the AO principles of fracture fixation should be adhered to. III.

Hypoxia Promotes Osteoclast Differentiation by Weakening USP18-Mediated Suppression on the NF-κB Signaling Pathway

Osteoporosis, a prevalent metabolic bone disorder, is characterized by reduced bone density and increased fracture risk. The pathogenesis of osteoporosis is closely associated with an imbalance in bone remodeling, in which the resorption function of osteoclasts exceeds the formation function of osteoblasts. Hypoxia has been implicated in the promotion of osteoclast differentiation and the subsequent development of osteoporosis. The ubiquitin–proteasome system (UPS) and its regulatory enzymes, deubiquitinating enzymes (DUBs), play a significant role in bone homeostasis. In this study, we investigated the contribution and mechanism of Ubiquitin-specific protease 18 (USP18), a DUB, in osteoclast differentiation under hypoxic conditions. BMDMs and RAW264.7 cells were treated with RANKL to induce osteoclastogenesis and were subjected to overexpression or knockdown of USP18 under normoxic or hypoxia conditions. Osteoclast formation was assessed using TRAP staining, and the expression of osteoclast marker genes was determined using qRT-PCR. The activation of the NF-κB signaling pathway was evaluated using immunoblotting. We found that hypoxia significantly enhanced the differentiation of BMDMs and RAW264.7 cells into osteoclasts, accompanied by a notable downregulation of USP18 expression. The overexpression of USP18 inhibited RANKL-induced osteoclast differentiation, while the knockdown of USP18 promoted that process, unveiling the inhibitory effect of USP18 in osteoclastogenesis. Furthermore, the overexpression of USP18 rescued the hypoxia-induced increase in osteoclast differentiation. Mechanistic insights revealed that USP18 inhibits osteoclastogenesis by suppressing the NF-κB signaling pathway, with a potential target on TAK1 or its upstream molecules. This study indicates that hypoxia promotes osteoclast differentiation through the downregulation of USP18, which, in turn, relieves the suppression of the activation of the NF-κB signaling pathway. The USP18 emerges as a potential therapeutic target for osteoporosis treatment, highlighting the importance of the hypoxia–DUB axis in the pathogenesis of the disease.

Effect of adipose tissue on the development of multiple myeloma.

Multiple myeloma(MM), also referred to as Kahler's disease, is a cancer characterized by the uncontrolled growth of abnormal plasma cells and is associated with alterations in the bone tissue microenvironment. Bone marrow adipose tissue (BMAT), which comprises approximately ten percent of total body fat, can influence the progression, survival, and drug resistance of MM cells through paracrine, hormonal, and metabolic pathways. Obesity can lead to an increase in BMAT mass, which not only disrupts bone metabolism but also reduces bone density, potentially progressing from monoclonal gammopathy of undetermined significance, a benign condition, to MM. A range of factors, including impaired fatty acid metabolism, increased production of adipokines that support myeloma, and heightened expression of oncogenic microRNAs in multiple myeloma, contribute to the progression of this incurable blood cancer. To better understand the relationship between excess adipose tissue accumulation and the risk of developing multiple myeloma, a comprehensive review of published data was conducted.

Asymmetrical Damage of the Wrist Joint Induces Lateralized Cortical Bone Loss in the Metacarpal Diaphysis in Patients with Rheumatoid Arthritis.

Background/Objectives: Osteoporosis is common in rheumatoid arthritis (RA), occurring either systemically or locally around inflamed joints. Decreased metacarpal bone density is a known marker of RA progression and hand function impairment. Although RA is generally characterized by symmetrical arthritis, some patients exhibit asymmetrical joint involvement. This study investigates the frequency of unilateral metacarpal bone density reduction in RA patients and aims to identify associated factors. Methods: This study included 143 RA patients (107 females, mean age 62.4 yrs., mean disease duration 11.1 yrs.). Bilateral hand X-rays were used to measure the cortical thickness rate (CTR) of the 2nd to 4th metacarpals. Unilateral bone density reduction was defined as a thin-to-thick-side CTR ratio (CTRR) < 0.8. Associations between CTR reduction and unilateral wrist joint damage (WJD) were analyzed. Results: Unilateral CTR reduction (CTRR < 0.8) was observed in 16.8% of patients, significantly associated with unilateral WJD. Among patients with unilateral WJD, 50.0% showed CTRR lateral (+) compared to 10.1% without unilateral WJD (p < 0.01). ANCOVA revealed significant effects of WJD laterality on CTRR, with an interaction effect showing greater CTRR laterality when thin-side WJD was present without thick-side WJD. Post-biologic treatment, CTR values decreased in both hands, indicating no improvement in bone density reduction. Conclusions: Approximately 17% of RA patients exhibited unilateral relative metacarpal bone density reduction, closely associated with unilateral WJD. This first detailed report on bone density laterality in RA underscores the need for early intervention and rehabilitation strategies in RA patients with hand involvement.

FEA-based Virtual Operation and Stress Distribution Analysis of DHS Screws in Proximal Femoral Bone Fractures: A Strategic Guide for Orthopedic Surgeons in Operational Planning

Background Accidents are the major reasons causing hip bone fractures. These are due to reduced bone density due to aging effect which may cause fractures typically in proximal part of the femur bone. Purpose The purpose of this work is to concentrate on preoperative planning by using a 3D model developed with a virtual operation using a dynamic hip screw (DHS). Methods DHS is generally preferred for the stabilization of stable fractures. The virtual operation was performed on the proximal femoral fracture site, typically for stable fractures. Finite element analysis (FEA) of operated bone was performed to estimate Von Misses stress distribution on the implant post-operatively, resulting in less stress on the fracture site. Results FEA indicates a transfer of stress of the fracture site (35–62%) on the implant, resulting in the operation’s success. Such work will assist orthopedic surgeons in determining load-bearing capacities after the mobilization of the patient. Conclusion Virtual surgery helps the surgeon to identify fracture geometry, the success of the operation, and proper fixation of the implant to avoid post-surgery complications. This aids in the quick recovery of patients, resulting in early rehabilitation.

Anterior chain activation and high intensity gait training to improve walking in an adult with cerebral palsy: a case report.

Adults living with Cerebral Palsy (CP) who are non-ambulatory are at increased risk for falls, contractures, reduced bone density, and pain. There is limited evidence for core strength training, anterior chain activation exercises, or high intensity gait training (HIGT) to improve gait function in adults with CP. The purpose of this case report is to describe the use of anterior chain muscle activation and HIGT to improve walking in a non-ambulatory adult male with quadriplegic CP. The participant was a 26 y.o. male living with spastic quadriplegic CP with a goal to cross the finish line of an adaptive triathlon while ambulating. The outpatient physiotherapy protocol emphasized anterior chain activation exercises and HIGT to improve strength, gait, and mobility at a frequency of 1-2 times a week for 8 months. The minimal detectable change of 19 points was achieved on the Function in Sitting Test (FIST). The original ambulation goal was exceeded to a maximum of 76 meters overground. The participant was able to walk across the finish line using a gait trainer while supervised at an adaptive triathlon. Focusing on anterior chain exercises and HIGT was effective to minimize extensor spasticity by strengthening body flexors allowing improved mobility and gait.

Dehydroepiandrosterone and Bone Health: Mechanisms and Insights.

Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal glands, plays a key role in various physiological processes, including bone health. Its age-related decline is linked to reduced bone density, though the mechanisms by which DHEA affects bone metabolism remain complex. This review summarises the diverse effects of DHEA on bone metabolism and density, highlighting its therapeutic potential; Methods: A literature search on the effects of DHEA on bone-related parameters was conducted from PubMed and Scopus using a specific search string, and after removing duplicates and irrelevant articles, 36 relevant full-text studies were included; Results: DHEA promotes osteoblast differentiation and proliferation, regulates the RANKL/OPG ratio, and inhibits osteoclastogenesis and bone resorption. Its osteogenic effects are mediated through multiple signalling pathways. In ovariectomised rat models, DHEA enhances trabecular bone volume, stimulates osteoblast proliferation, and increases oestradiol production and aromatase activity. In elderly individuals with low androgen levels, DHEA supplementation increases sulphated DHEA and oestradiol levels and improves bone mineral density, particularly in the ultra-distal radius of women and the femoral neck of men. However, the clinical use of DHEA remains debated due to inconsistent study results. Its effects on bone health may vary based on factors such as age, gender, and health conditions, emphasising the need for further research to clarify its mechanisms and optimise its use; Conclusions: In conclusion, while DHEA shows potential as a modulator of bone health, comprehensive clinical trials are required to assess its efficacy and safety, particularly in at-risk populations.

Marginal health care expenditures and health-related quality of life burden in patients with osteoporosis in the United States.

Osteoporosis, marked by reduced bone density, significantly impacts quality of life. Recent estimates on its economic and humanistic burden in the United States are scarce. To evaluate the marginal burden of osteoporosis on total all-cause health care costs and health-related quality of life (HRQoL) in the United States. This retrospective cross-sectional study utilized 2019-2021 Medical Expenditure Panel Survey data, including adults aged ≥50 years with or without osteoporosis. HRQoL was assessed using physical component summary (PCS) and mental component summary (MCS) scores. Descriptive analyses reported sociodemographic/clinical characteristics, healthcare expenditures, and PCS/MCS scores. A two-part model assessed the marginal effect of osteoporosis on total healthcare expenditures. Multivariable generalized linear model (GLM) estimated the marginal differences in MCS and PCS scores between the osteoporosis and nonosteoporosis groups, while multivariable linear regression assessed factors associated with HRQoL among patients with osteoporosis. There were approximately 2.89 million patients with osteoporosis and 25 million without osteoporosis. The marginal total health care expenditures were $8572.15 (95% CI: $6546.39-$14,597.92) higher for the osteoporosis Vs. nonosteoporosis group. Age, sex, marital status, year, and certain comorbidities were significant predictors of HRQoL among osteoporosis patients. Multivariable GLM indicated PCS scores were 6.29 units lower (95% CI:-7.08 to-4.15) and MCS scores were 4.22 units lower (95% CI:-8.34 to-3.31) among osteoporosis Vs. nonosteoporosis patients. Patients with osteoporosis showed higher economic burden and lower HRQoL than those without, highlighting the need for policy changes and innovative approaches to improve HRQoL and reduce healthcare expenses for osteoporosis management.

Unveiling the role of melatonin-related gene CSNK1D in osteoclastogenesis and its implications for osteoporosis treatment.

Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone density and quality, increasing fragility and fracture risk. Osteoclast (OC) activity and circadian rhythm play a role in the pathogenesis of OP. Melatonin is a circadian regulator that affects bone metabolism, but its molecular mechanism has not been studied in detail. This study aimed to identify the relationship between melatonin-related genes and OP through bioinformatics methods and to verify it experimentally.We analysed microarray data from the GSE35959 dataset, identifying differentially expressed genes in OP patients. Circadian rhythm-related genes and melatonin-related genes intersect with these differentially expressed genes, highlighting that CSNK1D is a central gene. Functional enrichment, correlation and protein-protein interaction analyses were conducted. Experimental validation involved in vitro differentiation assays using RAW264.7 cells and in vivo studies with an ovariectomy-induced rat model of OP to evaluate the role of CSNK1D in osteoclastogenesis to verify its effect on OP. Differential expression analysis revealed 272 significant genes, with CSNK1D identified as central to the circadian rhythm and to melatonin and OP interplay. Functional analyses showed involvement of CSNK1D in OC differentiation and inflammatory pathways. in vitro experiments confirmed CSNK1D upregulation during OC differentiation, and small interfering RNA-mediated knockdown reduced OC marker expression and TRAP+ cell formation. in vivo, CSNK1D expression is associated with bone loss in OP rats. Melatonin-related CSNK1D promotes OC differentiation and promotes the development of OP. These findings suggest CSNK1D as a potential therapeutic target for OP, offering insights into new treatment strategies integrating circadian rhythm regulation.

Effect of biomechanical load factors on the stress-strain state of teeth and underlying bone tissue

Background: The biomechanical conditions under which teeth, implants, and bone tissue function clearly determine their resistance to overloading and subsequent destruction. However, mathematical modeling has not previously been used to compare functional stress in teeth across a wide range of sensitive biomechanical load conditions. Aim: To compare the stress-strain state parameters of tooth and socket tissues under various biomechanical load conditions. Materials and methods: A mathematical model was used to assess the stress-strain state parameters of dental tissue and sockets under vertical and oblique load (150N) with various modeling settings, compared to reference model parameters. The following parameters were assessed: enamel attrition, bone density reduction, bone resorption by 30% and 50%, supra-occlusion, tooth cavity, composite restoration, and ceramic inlay. Results: Enamel attrition significantly increases stress under vertical and oblique loads: 1.9 and 1.6 times for enamel, and 1.5 and 1.2 times for dentin, respectively. Tooth cavities increase stress by 1.2 and 1.8 times (enamel; vertical and oblique loads, respectively), and 1.3 times (dentin; vertical load). Increased functional load causes a proportional increase in stress in hard tooth tissues and adjacent bone tissues. Supra-occlusion causes a sharp increase in stress in the enamel, with a point stress concentration. When a tooth cavity is filled with a composite or ceramic material, the stress-strain state parameters are similar to those in intact teeth (however, the enamel still experiences a 1.5-fold increase in stress under vertical pressure). Conclusion: 3D mathematical modeling revealed a significant difference in maximum stress in tooth and socket tissues compared to normal biomechanical conditions, as well as when comparing various sensitive load conditions. Stress in tooth and bone tissues increased in all cases of abnormal biomechanical conditions, especially when oblique load was applied.

Impact of microgravity and lunar gravity on murine skeletal and immune systems during space travel

Long-duration spaceflight creates a variety of stresses due to the unique environment, which can lead to compromised functioning of the skeletal and immune systems. However, the mechanisms by which organisms respond to this stress remain unclear. The present study aimed to investigate the impact of three different gravitational loadings (microgravity, 1/6 g [lunar gravity], and 1 g) on the behavior, bone, thymus, and spleen of mice housed for 25–35 days in the International Space Station. The bone density reduction under microgravity was mostly recovered by 1 g but only partially recovered by 1/6 g. Both 1 g and 1/6 g suppressed microgravity-induced changes in some osteoblast and osteoclast marker gene expression. Thymus atrophy induced by microgravity was half recovered by both 1 g and 1/6 g, but gene expression changes were not fully recovered by 1/6 g. While no histological changes were observed due to low gravity, alterations in gene expression were noted in the spleen. We found that in bone and thymus, lunar gravity reduced microgravity-induced histological alterations and partially reversed gene expression changes. This study highlighted organ-specific variations in responsiveness to gravity, serving as an animal test for establishing a molecular-level gravity threshold for maintaining a healthy state during future spaceflight.

Strength Training Among Male Master Cyclists-Practices, Challenges, and Rationales.

Background: Cycling performance declines with age due to reduced aerobic capacity, along with reductions in muscle mass and bone density. Strength training can help counter these effects. This study aims to explore the strength training practices, challenges, and decision-making rationale of male master cyclists to optimize performance and health as they age. Methods: A total of 555 male master cyclists aged 35 and above completed an online questionnaire, distributed via social media platforms, that included Likert-type, single- and multiple-selection, and open-ended questions. Participants were then divided into two age groups: 35-49 years (n = 359) and ≥50 years (n = 196). Analyses involved descriptive statistics, Wilcoxon signed-rank tests, Mann-Whitney U-tests, and chi-square tests, with qualitative data analyzed using content analysis. Results: More cyclists engaged in strength training during the off-/pre-season, with a significant reduction in both frequency and the number of cyclists engaging in strength training during the race season. The strength training practice was focused mainly on core and lower body, employing hypertrophy and maximal strength training methods. Key challenges included fatigue induced by strength training and limited time to perform strength training. The main rationale for the strength training revolved around improving cycling performance, reducing injury risk, and the health benefits of strength training. Both age categories, but the older group in particular, reported bone health as a primary rationale for strength training. Conclusions: While strength training offers performance and health benefits, issues of fatigue and time constraints remain substantial, suggesting the need for tailored training programs to improve adherence and effectiveness.