Reduced Bone Mass Research Articles

Interruption of mitochondrial symbiosis is associated with the development of osteoporosis

Mitochondria maintain bacterial traits because of their endosymbiotic origins, yet the host cell recognizes them as non-threatening since the organelles are compartmentalized. Nevertheless, the controlled release of mitochondrial components into the cytoplasm can initiate cell death, activate innate immunity, and provoke inflammation. This selective interruption of endosymbiosis as early as 2 billion years ago allowed mitochondria to become intracellular signaling hubs. Recent studies have found that the interruption of mitochondrial symbiosis may be closely related to the occurrence of various diseases, especially osteoporosis (OP). OP is a systemic bone disease characterized by reduced bone mass, impaired bone microstructure, elevated bone fragility, and susceptibility to fracture. The interruption of intra-mitochondrial symbiosis affects the energy metabolism of bone cells, leads to the imbalance of bone formation and bone absorption, and promotes the occurrence of osteoporosis. In this paper, we reviewed the mechanism of mitochondrial intersymbiosis interruption in OP, discussed the relationship between mitochondrial intersymbiosis interruption and bone marrow mesenchymal stem cells, osteoblasts and osteoclasts, as well as the inheritance and adaptation in the evolutionary process, and prospected the future research direction to provide new ideas for clinical treatment.

The Impact of Body Mass Index and Benign Prostatic Hyperplasia on Bone Health of Middle-Aged and Older Men.

Osteoporosis significantly affects older adults by reducing bone mass and increasing fracture risk, thereby impacting morbidity and mortality. This study aimed to investigate the relationship between bone mineral density (BMD), body mass index (BMI), and trabecular bone score (TBS) among middle-aged and older men with or without benign prostatic hyperplasia (BPH). A retrospective study was conducted using health examination data from male participants aged 50-98years collected at a regional hospital in southern Taiwan. Simple and multiple linear regression analyses were employed to examine the relationships between TBS and the independent variables. A total of 3714 middle-aged and older men were included in the analysis. Findings indicated that higher BMI was associated with greater BMD; however, the relationship with TBS suggested potential bone quality degradation in cases of underweight and obesity. Multiple linear regression analysis demonstrated that age, waist circumference, BMD, underweight status, and obesity were significantly associated with TBS. This study revealed the associative relationship between BMI and bone health: higher BMI was associated with increased bone density but also related to a decline in bone quality as measured by TBS, particularly in cases of obesity. These results emphasized the importance of managing BMI to optimize both bone density and quality, especially in middle-aged and older men with or at risk of BPH.

Circular RNAs in the management of human osteoporosis.

Osteoporosis (OP) is a metabolic bone disease producing reduction in bone mass with consequent bone fragility. Circular ribonucleic acid (CircRNA) is a form of RNA that forms a loop structure rather than a linear one. CircRNA can be used for therapeutic purposes, including molecular targets or to test new therapies. A systematic search of different databases to July 2024 was performed to define the role of circRNA in OP therapy. Seventeen suitable studies were identified. CircRNAs may be useful in studying metabolic processes in OP and identify possible therapeutic targets and new drug therapies. The metabolic processes involved in OP are regulated by many genes and cytokines that can be targeted by CircRNAs. However, it is not easy to predict whether the in vitro responses of the studied CircRNAs and their interaction with drugs are also applicable in vivo. Metabolic processes can be affected by gene dysregulation of CircRNAs on various growth factors. Areas timely for developing research: Despite the predictability of CircRNA pharmacological response in vitro, such pharmacological response cannot be expected to be replicated in vivo. The data that support the findings of this study are available from the corresponding author.

The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease.

Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.

The VDR rs1544410 and rs11568820 Variants and the Risk of Osteoporosis in the Polish Population.

Vitamin D affects bone metabolism and calcium-phosphate metabolism. Its deficiency leads to bone mineralization disorders and is the cause of abnormal skeletal development from fetal life to the period of completed skeletal growth. In later periods of life, vitamin D deficiency leads to bone metabolism disorders, i.e., osteoporosis. Disturbance of the balance between osteoblasts responsible for bone formation and osteoclasts associated with bone resorption results in reduced bone mass and bone weakening, and consequently leads to susceptibility to fractures. Analysis of genetic variants of the vitamin D receptor (VDR) concerns their relationship with metabolic bone diseases, and the results of previous studies assessing the relationship of polymorphisms with bone mineral density, fracture risk, or osteoporosis are not clear. Therefore, the aim of our study was to determine the effect of rs1544410 and rs11568820 polymorphisms of the VDR gene on the risk of developing osteoporosis in the Polish population. The study included 197 women with osteoporosis, 98 women with osteopenia, and 147 healthy controls. The real-time PCR method was used to determine the rs1544410 and rs11568820 polymorphisms of the VDR1 gene. Analysis of the results in the group with osteopenia showed that for the rs1544410 polymorphism, heterozygous GA genotypes occurred in 37.8% of the study group and 47.6% of the controls (OR = 0.60; 95%CI: 0.34-1.05), and homozygous AA in 15.3% of the study group and 17.0% of the controls (OR = 0.68; 95%CI: 0.32-1.44) (p = 0.185, AIC = 332.4; AIC-Akaike information criterion). The best model for this variant turned out to be the dominant model OR = 0.62; 95%CI: 0.37-1.04; p = 0.071, AIC = 330.5. In the case of the rs11568820 polymorphism of the VDR gene, the GG genotype was more common in women with osteopenia compared to controls (75.5% vs. 70.1%). Genotypes containing at least one mutant A allele were present in 24.5% of women with osteopenia and 29.9% of controls (OR = 0.76; 95%CI: 0.43-1.36; p = 0.349; AIC = 332.9). Analyzing the rs1544410 polymorphism in women with osteoporosis, the GA genotype was present in 42.1% of the study group and 47.6% of patients with normal bone density (OR = 0.74; 95%CI: 0.46-1.19), and the AA genotype in 15.7% of the study group and 17.0% of controls (OR = 0.78; 95%CI: 0.41-1.46) (p = 0.441). In the case of the rs11568820 polymorphism, the GA genotype occurred in 22.3% of the study subjects and 27.2% of the control patients (OR = 0.76; 95%CI: 0.46-1.25), and the AA genotype in 2.0% of the study subjects and 2.7% of the controls (OR = 0.69; 95%CI: 0.17-2.83) (p = 0.511). For both variants, the model with the lowest AIC value was the dominant model, in which for the rs1544410 variant OR = 0.75; 95%CI: 0.48-1.17; p = 0.203; AIC = 472.0 was obtained, while for rs11568820-OR = 0.75; 95%CI: 0.47-1.22; p = 0.250; AIC = 472.3. The obtained results indicate that the rs1544410 and rs11568820 polymorphisms of the VDR gene do not affect the development of osteoporosis in the Polish population.

Piezo1 expression in mature osteocytes is dispensable for the skeletal response to mechanical loading

Mechanical loading is essential for bone growth and homeostasis, with osteocytes considered the primary mechanosensors. Deleting the mechanosensitive ion channel Piezo1 from Dmp1-Cre-targeted cells, which include both osteoblasts and osteocytes, resulted in reduced bone mass and impaired skeletal responses to mechanical stimuli. To specifically isolate Piezo1's role in osteocytes, we used Sost-Cre mice to generate mice with Piezo1 deletion exclusively in mature osteocytes. These mice exhibited lower bone mineral density, decreased cancellous bone mass, and reduced cortical thickness with decrease periosteal expansion. However, unlike mice lacking Piezo1 in both osteoblasts and osteocytes, those with Piezo1 deletion in mature osteocytes responded normally to mechanical loading. These findings suggest that Piezo1 expression in mature osteocytes contributes to bone maintenance under normal physiological condition, but is dispensable for the skeletal response to mechanical loading.

Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.

Combined Romosozumab and Raloxifene treatment targets impaired bone quality in a male murine model of diabetic kidney disease.

Comorbid diabetes and chronic kidney disease create a complex disease state with multi-faceted impacts on bone health, primarily reduced bone mass and tissue quality. To reduce fracture risk in this growing population, interventions are needed that target both bone mass and quality. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mass and strength in a murine model of combined diabetes and CKD (DKD), while Raloxifene (RAL) is a mild anti-resorptive used to treat osteoporosis that has also been shown to increase bone mechanical properties by increasing bone bound water content. We aimed to test whether combined RAL and Romo treatment could improve bone quality in our murine model of DKD more than either treatment alone. Using a previously established streptozotocin- and adenine-diet-induced model, male, C57BL/6J mice were randomly divided into four treatment groups and given daily subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 0.5 mg/kg RAL. In addition, two groups were also given a weekly dose of Romo (10 mg/kg). Overall, Romo increased whole-bone strength and RAL improved tissue-level mechanical properties. Combined RAL-Romo treatment led to significantly higher cortical and trabecular bone mass compared to untreated controls. These morphological improvements created corresponding improvements in cortical bending strength and vertebral trabecular compression strength. These results suggest that combined RAL-Romo treatment provides both mass and quality improvements to DKD bone.

Roles of osteoclasts in pathological conditions.

Bone is a unique organ crucial for locomotion, mineral metabolism, and hematopoiesis. It maintains homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts, which is regulated by the basic multicellular unit (BMU). Abnormal bone metabolism arises from an imbalance in the BMU. Osteoclasts, derived from the monocyte-macrophage lineage, are regulated by the RANKL-RANK-OPG system, which is a key factor in osteoclast differentiation. RANKL activates osteoclasts through its receptor RANK, while OPG acts as a decoy receptor that inhibits RANKL. In trabecular bone, high turnover involves rapid bone formation and resorption, influenced by conditions such as malignancy and inflammatory cytokines that increase RANKL expression. Cortical bone remodeling, regulated by aged osteocytes expressing RANKL, is less understood, despite ongoing research into how Rett syndrome, characterized by MeCP2 abnormalities, affects RANKL expression. Balancing trabecular and cortical bone involves mechanisms that preserve cortical bone, despite overall bone mass reduction due to aging or oxidative stress. Research into genes like sFRP4, which modulates bone mass, highlights the complex regulation by BMUs. The roles of the RANKL-RANK-OPG system extend beyond bone, affecting processes such as aortic valve formation and temperature regulation, which highlight the interconnected nature of biological research.

Biochemical Mechanisms and Rehabilitation Strategies in Osteoporosis-Related Pain: A Systematic Review.

Osteoporosis causes a bone mass reduction and often determines acute and chronic pain. Understanding the biochemical and neurophysiological mechanisms behind this pain is crucial for developing new, effective rehabilitative and therapeutic approaches. This systematic review synthesizes recent advances in muscle-bone interactions and molecular pathways related to osteoporosis-associated pain. We carried out a systematic review including studies published from 2018 to 2024 using PubMed, Scopus, clinicaltrials.gov and Cochrane Library. The Cochrane Collaboration tool was used to assess bias risk. The review adhered to PRISMA guidelines and is registered with PROSPERO (CRD42024574456); Results: Thirteen studies were included. It emerged that osteoporosis causes progressive bone loss due to disruptions in biochemical processes and muscle-bone interactions. This condition is also closely associated with the development of pain, both acute and chronic. Key findings include the role of the miR-92a-3p/PTEN/AKT pathway and the impact of muscle-bone disconnection on bone health. Mechanotransduction is critical for bone maintenance. Effective pain management and rehabilitation strategies include physical therapy and physical exercise, yoga, Pilates, and cognitive behavioral therapy (CBT); they all improve pain relief and functional outcomes by enhancing muscle strength, flexibility, and balance. Pharmacological options such as NSAIDs, opioids, and new agents like SHR-1222, along with surgical interventions like percutaneous vertebroplasty, offer additional pain reduction, especially when included in individualized rehabilitation projects; Conclusions: This review highlights advancements in understanding osteoporotic pain mechanisms and identifies promising treatments. Integrating targeted therapies and rehabilitation strategies can enhance patients' pain relief.

Association of Osteoporosis with Tooth Loss and Dental Radiomorphometric Indices.

Background/Objectives: Osteoporosis is a systemic disease associated with reduced bone mass, impaired bone microarchitecture, and thus an increased risk of bone fractures. Moreover, patients with osteoporosis are more likely to experience periodontal diseases and tooth loss. Some indices have been proposed to detect osteoporosis on dental panoramic radiographs. The aim of our retrospective study was to investigate the association between osteoporosis and the loss of alveolar bone and teeth and to evaluate the validity of several dental radiomorphometric indices for assessing osteoporosis. Methods: In patients with and without osteoporosis, tooth loss, alveolar bone loss, the panoramic mandibular index (PMI), mental index (MI), and mandibular cortical index (MCI) were determined. Results: Compared with the non-osteoporotic group, patients with osteoporosis showed more tooth loss and more severe alveolar bone loss. PMI and MI were lower in patients with osteoporosis than in the non-osteoporotic group. Analysis of MCI showed that category C3 (cortical layer forms strong endosteal cortical residues and is clearly porous) was significantly more common in patients with osteoporosis. Conclusions: Osteoporosis is associated with more tooth and alveolar bone loss. Furthermore, various dental radiomorphometric indices are altered in osteoporosis and could thus help to better assess osteoporosis of the jaw.

Gene-Activating Framework Nucleic Acid-Targeted Upregulating Sirtuin-1 to Modulate Osteoimmune Microenvironment for Diabetic Osteoporosis Therapeutics.

Diabetic osteoporosis, a prevalent chronic complication of diabetes, is marked by reduced bone mass, increased bone fragility, and susceptibility to fractures. A significant cause of this condition is the disruption of osteoblastic homeostasis due to prolonged hyperglycemia, which impedes bone regeneration and remodeling. Despite its prevalence, no effective treatments specifically target diabetic osteoporosis. Recently, small-activating RNA (saRNA) therapy has attracted attention for its targeting capacity, high efficacy, and minimal side effects. However, RNA's inherent properties, such as structural instability, susceptibility to degradation, and poor penetration, limit its applications. To address these limitations, a gene-activating tetrahedral framework nucleic acid (tFNA) with sirtuin-1 (SIRT1) gene activation function is developed, termed Tsa. Tsa exhibits an RNA-protecting effect and can effectively penetrate cell membranes to upregulate SIRT1 gene expression. At the histological level, Tsa treatment alleviates diabetic osteoporosis by increasing bone trabecular density and promoting new bone formation. At the cellular level, it switches macrophage polarization toward the anti-inflammatory M2 phenotype while inhibiting the inflammatory M1 phenotype, creating a favorable bone immune microenvironment for osteoblasts. At the genetic level, Tsa activates SIRT1 expression, which deacetylates Acetyl-p65 to block the NF-κB pathway and restore the osteoimmune environment. Overall, this research demonstrates a nanodrug "Tsa", capable of activating SIRT1 and modulating the bone immune environment, thereby showcasing its immense potential for diabetic osteoporosis treatment.

The Nexus Between Traditional Chinese Medicine and Immunoporosis: Implications in the Treatment and Management of Osteoporosis.

Osteoporosis (OP) is a globally prevalent bone disease characterized by reduced bone mass and heightened fracture risk, posing a significant health and economic challenge to aging societies worldwide. Osteoimmunology-an emerging field of study-investigates the intricate relationship between the skeletal and the immune systems, providing insights into the immune system's impact on bone health and disease progression. Recent research has demonstrated the essential roles played by various immune cells (T cells, B cells, macrophages, dendritic cells, mast cells, granulocytes, and innate lymphoid cells) in regulating bone metabolism, homeostasis, formation, and remodeling through interactions with osteoclasts (OC) and osteoblasts (OB). These findings underscore that osteoimmunology provides an essential theoretical framework for understanding the pathogenesis of various skeletal disorders, including OP. Traditional Chinese medicine (TCM) and its active ingredients have significant clinical value in OP treatment. Unfortunately, despite their striking multieffect pathways in the pharmacological field, current research has not yet summarized them in a comprehensive and detailed manner with respect to their interventional roles in immune bone diseases, especially OP. Consequently, this review addresses recent studies on the mechanisms by which immune cells and their communication molecules contribute to OP development. Additionally, it explores the potential therapeutic benefits of TCM and its active components in treating OP from the perspective of osteoimmunology. The objective is to provide a comprehensive framework that enhances the understanding of the therapeutic mechanisms of TCM in treating immune-related bone diseases and to facilitate the development of novel therapeutic strategies.

Role of microRNA in Diabetic Osteoporosis.

Diabetic osteoporosis (DOP), a complication associated with diabetes mellitus (DM), is a metabolic bone disorder characterized by a reduction in bone mass per unit volume, impaired bone tissue microarchitecture, heightened bone fragility, and increased susceptibility to fractures. Individuals with diabetes exhibit a significantly greater incidence of osteoporosis and related fractures than those without diabetes. These fractures present a significant challenge in terms of the healing process and can result in severe consequences, including fatalities. MicroRNAs (miRNAs), a class of noncoding RNAs, play a pivotal role in numerous human diseases and are implicated in the pathogenesis of DOP. This review initially elucidates the essential role of miRNAs in the pathogenesis of DOP. Next, we emphasize the potential significance of miRNAs as valuable biomarkers for diagnosing DOP and predicting DOP-related fractures. Furthermore, we explore the involvement of miRNAs in managing DOP through various pathways, including conventional pharmaceutical interventions and exercise therapy. Importantly, miRNAs exhibit potential as targeted therapeutic agents for effectively treating DOP. Finally, we highlight the use of novel materials and exosomes for miRNA delivery, which has significant advantages in the treatment of DOP and overcomes the limitations associated with miRNA delivery.

Prenatal dexamethasone exposure reduces osteoprogenitor proliferation in mice via histone modifications at the Mkp-1 gene locus

Prenatal dexamethasone exposure (PDE) has long-term consequences in bone development, though the underlying mechanisms remain unclear. Our results show that PDE offspring exhibit reduced bone mass, fewer osteoblasts and diminished osteoprogenitors proliferation. Further analyses show that PDE increases MKP-1 expression, while decreasing H3 lysine 9 dimethylation (H3K9me2) and H3 lysine 27 trimethylation (H3K27me3) at the Mkp-1 gene locus. Mechanistically, dexamethasone suppresses osteoprogenitors proliferation by upregulating MKP-1 expression, notably through the inhibition of H3K9me2 and H3K27me3 modifications, which promote demethylation and transcriptional activation of the Mkp-1 gene. Importantly, restoring histone methylation balance with PFI-90 or GSK-J4 treatment blocks the inhibitory effects of PDE on MAPK signaling in osteoprogenitors, and mitigates the detrimental impact of PDE on osteoprogenitor proliferation and bone development in the offspring. This study provides new insights into the epigenetic mechanism by which PDE disrupts long-term programming of fetal osteoprogenitor proliferation, ultimately impairing long bone growth in offspring.

Novel approach to bone comorbidity in resistant acromegaly.

Active acromegaly may lead to irreversible complications. Among them, acromegaly osteopathy and fragility (vertebral and hip) fractures have emerged as frequent and precocious events in the natural history of the disease, being correlated with longer disease duration and higher growth hormone (GH) levels, accounting for patients' reported poor quality of life, physical performance and other life-impacting complications. Differently from primary osteoporosis, bone mineral density is not a reliable tool to predict fracture risk in this clinical setting, as patients with active disease frequently have normal or slightly reduced bone mass; whereas bone quality is particularly compromised, as determined by low trabecular bone score (TBS) in patients with active disease as compared to healthy controls or patients with cured/controlled disease. The evidence of impaired bone microstructure has been profoundly investigated with different computed tomography (CT) techniques, reporting low trabecular number and thickness as well as wide but more porous cortical bone, providing an explanation for such a high prevalence of vertebral fractures (up to 40-50% in selected cohorts). Since data on bone-active drugs are scanty, disease control remains a cornerstone to prevent fractures. Nonetheless, some potential protective effects may derive from vitamin D supplementation and pasireotide therapies, independently from disease status. Aim of this manuscript is to review the current and emerging evidence on skeletal fragility in patients with active and resistant acromegaly.

BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization

Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.

Influence of disease activity and gonadal status on bone mineral density and turnover in acromegaly.

The purpose of this study was to evaluate the impact of disease activity and gonadal status on bone mineral density (BMD) and turnover markers (BTMs) in individuals with acromegaly. Subjects underwent laboratory tests for PTH, 25-hydroxyvitamin D, calcium, phosphorus, osteocalcin (OC) and C-telopeptide (CTX-1) and bone densitometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Sixty participants (48.6 ± 11.0years; 66,7% female) were included in this cross-sectional study. Phosphorus, OC, CTX-1, and LS BMD were greater in the active disease group than in the controlled/cured disease group (P = 0.025, P < 0.001, P = 0.007, and P = 0.016, respectively). When analyzing gonadal status, phosphorus, OC and CTX-1 were greater in the hypogonadal group than in the eugonadal group (P = 0.017, P = 0.015, and P = 0.033, respectively). Patients with hypogonadism had a higher prevalence of reduced bone mass compared to eugonadal patients (44 vs. 17%, P = 0.023). This study revealed increased levels of phosphorus and BTMs in patients with active acromegaly. In this group, the greater LS BMD values are likely due to the anabolic effects of GH and IGF-1 and/or to the influence of LS arthropathy. Moreover, hypogonadism negatively impacts bone metabolism in acromegaly, leading to elevated BTMs and a higher prevalence of reduced bone mass in individuals affected by both conditions.

Effects of Aging on the Immune and Periosteal Response to Fracture in Mice.

Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly and linked to high mortality. Understanding how aging affects fracture healing is essential for developing therapies to enhance bone regeneration in older adults. During the inflammatory phase of fracture healing, immune cells are recruited to the injury site as periosteal skeletal stem/progenitor cells (pSSPCs) rapidly proliferate and differentiate into osteochondral lineages, allowing for fibrocartilaginous callus formation and complete bone healing. Irrespective of age, how periosteal mesenchymal and immune cells interact during early fracture healing is incompletely understood, limiting our ability to potentially modulate these processes. To address this, we directly analyzed, in parallel, at a single-cell level, isolated murine CD45(+) and CD45(-) periosteal cells dissected from intact and fractured bones, collected three days after injury. Through comprehensive analysis, corroborated by bulk RNA-sequencing, flow cytometry, and histology, we found aging decreases pSSPCs proliferative, marked by a reduced expression of genes required for callus formation and an increased senescence signature. We found that the chemokine Cxcl9 was highly upregulated in aged intact Prrx1+ pSSPCs, predicted to interact with other pSSPCs directly, and associated with increased recruitment of CD8+ T cells at the fracture site three days after injury. Cell-to-cell communication analysis provided insight into the complexity of interactions among the many cell types regulating fracture healing and the impact of aging on these processes. Together, these results provide insight into age-induced alterations in fracture healing, informing the development of improved therapeutic approaches for fragility fractures.

Effects of Creatine Monohydrate Supplementation on Muscle, Bone and Brain- Hope or Hype for Older Adults?

Sarcopenia, generally characterized by the age-related reduction in muscle strength, lean/muscle mass and functional ability, is also associated with reduced bone mass and strength and impaired brain health and function. One potential intervention which has received much 'hype' over the past few decades to countermeasure these negative consequences of biological aging is creatine monohydrate supplementation. From a skeletal muscle perspective, the combination of creatine monohydrate supplementation and resistance training provides 'hope' for older adults as it improves measures of lean mass, regional (limb) muscle thickness, upper- and lower-body muscle strength and functional ability. Further, there is some evidence that creatine (supplementation or habitual diet) provides a ray of 'hope' for improving some aspects of cognitive function. The majority of research suggests that creatine is more 'hype' than 'hope' for improving measures of bone mass in older adults. Creatine monohydrate supplementation provides some anti-sarcopenic benefits for older adults.