[Equality across ages : addressing gender discrimination among older patients]. / Égalité à tous les âges : aborder la discrimination de genre chez les patient-e-s âgé-e-s.

The aim of this article is to draw attention to sex- and gender-related differences in the management of elderly patients. This issue is illustrated with two diseases linked to gender and sex: osteoporosis and high blood pressure. On one hand, patients of the sex less affected by the disease may feel less concerned; on the other hand, these patients are at greater risk of being under-diagnosed by medical and nursing staff. In addition, studies tend to overlook patients of the less-affected sex, resulting in guidelines that do not take account of sex or gender specific characteristics. There is even less literature on gender-related disparities in care in the elderly population than in the young, but it can be assumed that this risk of disparities exists even more in relation to specificities in diagnosis and care of elderly patients.

Cet article vise à attirer l'attention sur le risque de différences de prise en charge des patient-e-s âgé-e-s liées au sexe et au genre, illustré par deux pathologies considérées l'une comme féminine, l'autre comme masculine : l'ostéoporose et l'hypertension artérielle. Dans ce type de pathologies, les patient-e-s du sexe le moins touché par la maladie peuvent se sentir moins concerné-e-s et ont un risque accru de sous-diagnostic de la part du corps médicosoignant. De plus, les études tendent à négliger les patient-e-s du sexe moins touché, aboutissant à des guidelines ne tenant pas compte de spécificités liées au sexe ou au genre. La littérature sur les disparités de prise en charge liées au genre dans la population âgée est encore très limitée. Néanmoins, il est important de prendre en compte les spécificités liées au genre au même titre que celles liées à l'âge avancé.

Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis and remains an incurable fatal disease. Therefore, the identification of molecular markers involved in cancer progression is urgently needed to develop more-effective therapies. The present study investigated the role of the Wnt signaling modulator Dickkopf-1 (DKK1) in the growth and metastatic progression of mCRPC. DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in two different metastatic castration-resistant prostate cancer cell lines (PC3 and DU145). A xenograft tumor model was used to assess tumor growth and metastases. In in vitro experiments, both DKK1 silencing and deletion reduced cell growth and migration of both cell lines. DKK1 knockout clones (DKK1-KO) exhibited cell cycle arrest, tubulin reorganization, and modulation of tumor metastasis-associated genes. Furthermore, in DKK1-KO cells, E-cadherin re-expression and its membrane co-localization with ß-catenin were observed, contributing to reduced migration; Cadherin-11, known to increase during epithelial-mesenchymal transition, was down-regulated in DKK1-KO cells. In the xenograft mouse model, DKK1 deletion not only reduced tumor growth but also inhibited the formation of lung metastases. In conclusion, our findings support the key role of DKK1 in the growth and metastatic dissemination of mCRPC, both in vitro and in vivo.

A contribution to the French validation of the clinical anxiety scale amongst health care workers in Switzerland.

BACKGROUND: Anxiety disorders are frequent but remain often underdiagnosed and undertreated. Hence, valid screening instruments are needed to enhance the diagnostic process. The Clinical Anxiety Scale (CAS) is a 25-item anxiety screening tool derived from the Hamilton Anxiety Scale (HAM-A). However, this scale is not available in French. The General anxiety disorder - 7 (GAD-7) scale, which has been validated in French, is a 7-item instrument with good psychometric properties. This study contributes to the validation of an adapted French version of the CAS, using the GAD-7 as the reference. METHODS: A forward-backward English-French-English translation of the CAS was performed according to standard practice. The French versions of the CAS and GAD-7 were completed by 127 French speaking healthcare professionals. CAS internal consistency was assessed using Crohnbach's alpha, and test-retest reliability was tested after 15 days in a subsample of 30 subjects. Convergent validity with GAD-7 was assessed using Pearson's correlation coefficient. Test-retest reliability was explored using one-way random effects model to calculate the intra-class correlation coefficient (ICC). RESULTS: French CAS showed excellent internal consistency (Cronbach's alpha 0.97), high convergent validity with GAD-7 (Pearson's R 0.81, p < 0.001), and very good test-retest reliability (ICC = 0.97, 95% CI 0.93-0.98). CONCLUSION: The proposed French version of the CAS showed high reliability and validity that need to be further investigated in different populations.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Using sequential pharmacotherapy for the treatment of osteoporosis: an update of the literature.

INTRODUCTION: Osteoporosis, which is characterized by compromised bone density and heightened susceptibility to fractures, is a substantial public health concern, especially among the aging population. Underdiagnosis, undertreatment, and therapy non-adherence contribute to its impact. Anabolic and dual-action agents like teriparatide, abaloparatide, and romosozumab have emerged as effective treatments, allowing rapid gains in bone mineral density (BMD) and reducing fracture risk. However, administering treatments in the correct order is paramount, with an 'anabolic first' approach gaining traction for patients at high risk of fractures. This strategy involves starting anabolic therapies, followed by antiresorptive agents as maintenance therapy. It is important to note that the effectiveness of anabolic agents differs between treatment-naive and previously treated patients: tailored treatment approaches are therefore necessary. This comprehensive strategy adheres to clinical guidelines, emphasizing individualized care, early intervention, and patient-centered management to mitigate the burden of osteoporosis and enhance patients' quality of life. AREA COVERED: The aim of this review is to summarize recent evidence on the sequential treatment of osteoporosis and to provide recommendations on the best treatment strategies. EXPERT OPINION: Effective treatments, such as anabolic agents, are key in high-risk patients, who require an 'anabolic first' approach. Sequential therapy, specifically tailored to a patient's history, can help to optimize prevention and management of fractures.

[Estimating renal function in older patients : which is the best formula?] / Estimation de la fonction rénale chez la personne âgée : quelle formule utiliser ?

An accurate assessment of renal function is crucial for the diagnosis and follow up of kidney diseases. However, there is currently no clear consensus on the optimal method on how to measure renal function in older individuals (>65 years of age). The Cockcroft-Gault formula, the MDRD equation, and the CKD-EPI equation are among the most used equations. However, they have several limitations when applied to the older population. Other formulas specifically developed for the older, such as the Berlin Initiative Study (BIS) and the Full Age Spectrum (FAS) equation, demonstrated conflicting results and require more external validation. This article provides an overview of the currently available methods to assess renal function in the older persons and summarizes their shortcomings.

Une évaluation correcte de la fonction rénale est essentielle pour diagnostiquer et prendre des décisions cliniques importantes. Cependant, il n'y a pas de consensus clair sur la meilleure méthode pour mesurer la fonction rénale chez les personnes âgées. Les équations les plus couramment utilisées sont la formule de Cockcroft-Gault et les équations MDRD et CKD-EPI, mais elles présentent des limitations dans cette population. D'autres formules spécifiquement développées pour les aînés, telles que l'étude de l'initiative de Berlin (BIS) et l'équation du spectre complet de l'âge (FAS), ont montré des résultats contradictoires et nécessitent des études de validation externe. En conclusion, les médecins doivent être conscients des différentes options disponibles et des limitations de chaque méthode pour prendre des décisions cliniques éclairées.

The Role of Nutrition in the Treatment of Sarcopenia in Old Patients: From Restoration of Mitochondrial Activity to Improvement of Muscle Performance, a Systematic Review.

Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.

Hyponatremia and aging-related diseases: key player or innocent bystander? A systematic review.

BACKGROUND: Hyponatremia is frequent in older age; whether it is a key player, a surrogate marker, or an innocent bystander in age-related diseases is still unclear. OBJECTIVE: To understand the role of hyponatremia in falls, osteoporosis, fractures, and cognitive impairment in old patients. METHOD: Eligibility criteria for study inclusions were: written in English, peer-reviewed observational and intervention studies, clinical trial, prospective and retrospective controlled cohort studies, and case-controlled studies without limitations regarding the date of publication. INFORMATION SOURCES: Protocol available on the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021218389). MEDLINE, Embase, and PsycINFO were searched. Final search done on August 8, 2021. Risk-of-bias assessment: Risk-of-Bias Assessment tool for Non-randomized Studies (RoBANS) and the Bradford Hill's criteria for causality. RESULTS: Includes studies: One-hundred thirty-five articles retained for the revision. Synthesis of results - Falls: Eleven studies were included. Strong association between hyponatremia and falls in all the studies was found. Osteoporosis and fractures: nineteen articles were included. The association between hyponatremia and osteoporosis is unclear. Cognitive impairment: Five articles were included. No association between hyponatremia and cognitive impairment was found. DISCUSSION: Interpretation: Falls, osteoporosis, and fractures are multifactorial. Hyponatremia is not temporally related with the outcomes; we suggest that hyponatremia may be regarded as a marker of unhealthy aging and a confounder instead of a causal factor or an innocent bystander for falls and fractures. Concerning cognitive impairment, there are no evidence supporting a real role of hyponatremia to be regarded as an innocent bystander in neurodegeneration.

Risk Factors for Early Hospital Readmission in Geriatric Patients: A Systematic Review.

The number of older patients is constantly growing, and early hospital readmissions in this population represent a major problem from a health, social and economic point of view. Furthermore, the early readmission rate is often used as an indicator of the quality of care. We performed a systematic review of the literature to better understand the risk factors of early readmission (30 and 90 days) in the geriatric population and to update the existing evidence on this subject. The search was carried out on the MEDLINE, EMBASE and PsycINFO databases. Three independent reviewers assessed the potential inclusion of the studies, and then each study was independently assessed by two reviewers using Joanna Briggs Institute critical appraisal tools; any discrepancies were resolved by the third reviewer. Studies that included inpatients in surgical wards were excluded. Twenty-nine studies were included in the review. Risk factors of early readmission can be classified into socio-economic factors, factors relating to the patient's health characteristics, factors related to the use of the healthcare system and clinical factors. Among these risk factors, those linked to patient frailty play an important role, in particular malnutrition, reduced mobility, risk of falls, fatigue and functional dependence. The early identification of patients at higher risk of early readmission may allow for targeted interventions in view of discharge.

Musculoskeletal Diseases Role in the Frailty Syndrome: A Case-Control Study.

Frailty syndrome severely burdens older age, and musculoskeletal diseases are of paramount importance in its development. The aim of this study is to unravel the contribution of musculoskeletal diseases to frailty syndrome. This is a case-control study, and we enrolled 55 robust community-dwelling age- and gender-matched patients, with 58 frail and pre-frail subjects. Frailty was diagnosed according to the Fried criteria (FP), and the Fragility Index (FI) was calculated. In all the subjects, a comprehensive geriatric assessment was carried out. Their nutritional status was evaluated by the Mini Nutritional Assessment and Bioelectrical Impedance Analyses. Their bone density (BMD), bone turnover, muscle mass, strength and performance were evaluated. Here, we show that the prevalence of frailty varies according to the diagnostic criteria used and that FP and FI showed a moderate to good agreement. Despite age and gender matching, frail subjects had lower muscle strength, performance and BMD. Their quality of life and cognitive performance were reduced in the frail subjects compared to the robust ones. Muscular strength and performance, together with mood, significantly predicted the diagnosis of frailty, whereas BMD and bone turnover did not. In conclusion, we show that sarcopenia plays a pivotal role in predicting the diagnosis of frailty, whereas osteoporosis does not.

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study.

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Fighting social isolation in times of pandemic COVID-19: the role of video calls for older hospitalized patients.

BACKGROUND: Loneliness and social isolation are associated with anxiety and psychological discomfort, especially amongst the oldest and fragile persons. AIMS: SILVER evaluates the acceptance of video calls by old hospitalized patients and their relatives during the ban on visits due to the COVID-19. Moreover, SILVER evaluates if the use of different communication technology is associated with different outcomes in terms of anxiety, fear of self and of others' death and mood. METHODS: SILVER is an observational multicentre study. Patients hospitalized in two geriatric units in Switzerland and in one orthogeriatric unit in Italy and their relatives were enrolled. Participants can freely choose to use phone or video calls and were evaluated over a week. We measured anxiety, fear of death and mood at baseline and at the end of the study with standard scales. The use of video or phone calls was associated to a change in these parameters by two-way ANOVA for repeated measures. RESULTS: Sixty-four patients and relatives were enrolled, 26.5% used phone calls and 73.5% video calls. The use of video calls was associated with a reduction in anxiety and fear of death in patients and relatives as compared to participants using phone calls. DISCUSSION: Old patients and their relatives accepted and appreciated the use of video calls during hospitalization; moreover, participant using video calls appears to be less anxious and less afraid of death. CONCLUSIONS: Video calls may be a useful communication tool for hospitalized older patients to keep social relationships with relatives and reduce their anxiety and fear of death. TRIAL REGISTRATION: Retrospectively registered on 1st September 2021 in ClinicalTrials.gov (NCT05000099).

From the Bench to the Bedside: Branched Amino Acid and Micronutrient Strategies to Improve Mitochondrial Dysfunction Leading to Sarcopenia.

With extended life expectancy, the older population is constantly increasing, and consequently, so too is the prevalence of age-related disorders. Sarcopenia, the pathological age-related loss of muscle mass and function; and malnutrition, the imbalance in nutrient intake and resultant energy production, are both commonly occurring conditions in old adults. Altered nutrition plays a crucial role in the onset of sarcopenia, and both these disorders are associated with detrimental consequences for patients (e.g., frailty, morbidity, and mortality) and society (e.g., healthcare costs). Importantly, sarcopenia and malnutrition also share critical molecular alterations, such as mitochondrial dysfunction, increased oxidative stress, and a chronic state of low grade and sterile inflammation, defined as inflammageing. Given the connection between malnutrition and sarcopenia, nutritional interventions capable of affecting mitochondrial health and correcting inflammageing are emerging as possible strategies to target sarcopenia. Here, we discuss mitochondrial dysfunction, oxidative stress, and inflammageing as key features leading to sarcopenia. Moreover, we examine the effects of some branched amino acids, omega-3 PUFA, and selected micronutrients on these pathways, and their potential role in modulating sarcopenia, warranting further clinical investigation.

Association between Immunosenescence, Mitochondrial Dysfunction and Frailty Syndrome in Older Adults.

Aging is associated with changes in the immune system, increased inflammation and mitochondrial dysfunction. The relationship between these phenomena and the clinical phenotype of frailty is unclear. Here, we evaluated the immune phenotypes, T cell functions and mitochondrial functions of immune cells in frail and robust older subjects. We enrolled 20 frail subjects age- and gender-matched with 20 robust controls, and T cell phenotype, response to immune stimulation, cytokine production and immune cell mitochondrial function were assessed. Our results showed that numbers of CD4+ and CD8+ T cells were decreased in frail subjects, without impairment to their ratios. Memory and naïve T cells were not significantly affected by frailty, whereas the expression of CD28 but not that of ICOS was decreased in T cells from frail subjects. T cells from robust subjects produced more IL-17 after CD28 stimulation. Levels of serum cytokines were similar in frail subjects and controls. Mitochondrial bioenergetics and ATP levels were significantly lower in immune cells from frail subjects. In conclusion, we suggest that changes in T cell profiles are associated with aging rather than with frailty syndrome; however, changes in T cell response to immune stimuli and reduced mitochondrial activity in immune cells may be considered hallmarks of frailty.

[To D or not to D ? Why and how to treat vitamin D deficiency in older patients]. / « To D or not to D ¼ : pourquoi et comment traiter l'hypovitaminose D chez les personnes âgées.

Vitamin D deficiency is so frequent in older patients (aged 65 years and older) that the international consensus does not recommend routine vitamin D measurement. Assessment of overall health status is a cornerstone before considering vitamin D supplementation, as the effect of vitamin D supplementation has only been demonstrated in vulnerable or dependent but not for robust older patients. The effect of the different modalities of oral vitamin D supplementation are equivalent : 800-1'200 IU/day, 10'000 IU/week or 30'000-50'000 IU/month. Monitoring of vitamin D blood level monitoring is not necessary because of a large therapeutic margin. In the presence of osteoporosis, a dietary or supplementation intake of 1'200 mg per day of calcium should be added.

L'hypovitaminose D est très fréquente chez les personnes âgées (65 ans et plus), à tel point que le consensus international est de ne pas doser la vitamine D en routine. L'évaluation de l'état de santé global est primordiale avant d'envisager une supplémentation en vitamine D, son effet ayant été démontré seulement chez les personnes âgées vulnérables ou dépendantes, mais pas chez les robustes. L'efficacité des modalités de supplémentation en vitamine D per os sont équivalentes : 800-1200 UI/jour, 10 000 UI/semaine ou 30 000-50 000 UI/mois. Un monitoring du taux sanguin de vitamine D n'est pas nécessaire en raison d'une large marge thérapeutique. En présence d'une ostéoporose, cette supplémentation devrait être complétée par un apport alimentaire ou une supplémentation de 1200 mg de calcium par jour.

The doll therapy as a first line treatment for behavioral and psychologic symptoms of dementia in nursing homes residents: a randomized, controlled study.

BACKGROUND: Patients living with dementia are severely affected by the development of behavioral and psychologic symptoms (BPSD) which represent a burden for patients and caregivers. The use of psychotropic drugs in the control of BPSD is widely diffused, however the use of a first line non-pharmacologic approach is highly recommended. Here we evaluate the effect of doll therapy (DT) in the management of BPSD, on the reduction of caregiver burden and delirium incidence in nursing home residents by a randomized controlled trial. METHODS: We enrolled fifty-two nursing homes residents living with dementia and BPSD. Subjects were randomized to DT (26) or standard treatment (ST, 26), we measured BPSD, caregiver burden and delirium with standard clinical scales at baseline, after 45 and 90 days. In order to evaluate the presence of BPSD we used Neuropsychiatric Inventory (NPI) scale and the A.Di.CO scale, the caregiver burden was measured by the Greutzner scale and delirium by the Confusion Assessment Method (CAM) scale. RESULTS: DT was more effective in reducing agitation and aggressiveness as respect to ST. Moreover DT globally reduced the presence of BPSD as dysphoria, wandering and apathy. We observed a significant reduction of the professional caregiver burden and the incidence of delirium was significantly reduced in subjects treated with DT. CONCLUSIONS: We show that DT is more effective that ST in the control of BSPD in patients affected by moderate to severe dementia. Moreover we suggest that DT may effective in reducing the incidence of delirium. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov the 10th June 2, 2021 trial registration number NCT04920591.

Vitamin D Deficiency and Risk of Metabolic Syndrome in Aging Men.

The elderly population is rapidly increasing; hence, the disability due to age-related diseases has become an important socioeconomic burden. Amongst age-related diseases cardiovascular ones (CVD) have a huge impact on morbidity and mortality and are associated with metabolic syndrome (MetS). Several studies investigated the role of hypovitaminosis D in the pathogenesis of MetS and of CVD, this review unravels the relationship between aging/senescence, vitamin D, gender, and pathogenesis of MetS.

Circulating Long Non-Coding RNA GAS5 Is Overexpressed in Serum from Osteoporotic Patients and Is Associated with Increased Risk of Bone Fragility.

Osteoporosis (OP) is a multifactorial disorder in which environmental factors along with genetic variants and epigenetic mechanisms have been implicated. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of bone metabolism and OP aetiology. In this study, we analyzed the expression level and the genetic association of lncRNA GAS5 in OP patients compared to controls. Quantitative RT-PCR analysis of GAS5 was performed on the serum of 56 OP patients and 28 healthy individuals. OP subjects were divided into three groups of analysis: 29 with fragility fractures of lumbar spine (OP_VF), 14 with fragility fractures of femoral neck (OP_FF) and 13 without fractures (OP_WF). Genotyping of the rs145204276 insertion/deletion polymorphism has also been performed by Restriction fragment length polymorphism (RFLP) and direct sequencing analyses. Expression of circulating GAS5 is significantly increased in OP patients compared to controls (p < 0.01), with a statistically higher significance in fractured OP individuals vs. healthy subjects (p < 0.001). No statistically significant change was found in female OP patients; conversely, GAS5 is upregulated in the subgroup of fractured OP women sera (p < 0.01) and in all OP males (p < 0.05). Furthermore, a direct correlation between GAS5 expression level and parathyroid hormone (PTH) concentration was found in OP patients (r = 0.2930; p = 0.0389). Genetic analysis of rs145204276 revealed that the deletion allele was correlated with a higher expression of GAS5 in OP patients (0.22 ± 0.02 vs. 0.15 ± 0.01, ** p < 0.01). Our results suggest circulating GAS5 as a putative biomarker for the diagnosis and prognosis of OP and OP-related fractures.