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Osteoporotic fracture has been understudied in men. In US male veterans aged 50 years and older between 2002 and 2019, hip fracture incidence increased between 2006 and 2019, fewer than 6% of men underwent DXA, and fewer than 0.5% of men were treated. Investigation of low screening and treatment rates is warranted. PURPOSE: In the United States, the annual incidence of osteoporotic hip fracture is estimated to be 250,000 to 300,000; the one-year mortality in some studies has been as high as 32%. Reports that hip fracture rates in US women 65 years and older may no longer be declining led to this investigation of hip fracture in men, a less studied population. We assessed the trends in the incidence of hip fracture in US male veterans 50 years and older of age as well as the rates of diagnosis and treatment in such men. METHODS: We assessed the recent trends of hip fracture incidence in a nation-wide male veteran population 50 years and older of age. Using data from the US Veterans Affairs Informatics and Computing Infrastructure (VINCI) 2002-2019, we calculated the annual age-standardized hip fracture incidence. Secondary objectives included evaluating the annual proportion of hip fracture patients who underwent dual-energy X-ray absorptiometry (DXA) before or after the fracture and/or received osteoporosis medication after the hip fracture over the study period. RESULTS: Hip fracture incidence increased in male veterans from 2006 to 2019. Fewer than 6% of men underwent a DXA scan and fewer than 0.5% received osteoporosis medications up to two years after a hip fracture. CONCLUSIONS: Despite available screening methods such as DXAs and medications for primary and secondary prevention of osteoporotic fractures, hip fracture incidence is not decreasing in older male veterans. Our study highlights a need for closer attention to fracture risk in men.

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CONTEXT: People living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. OBJECTIVE: To determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DESIGN: Cross-sectional analyses of bone properties in people with SCI. PARTICIPANTS: Twenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). OUTCOME MEASURES: Distal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (µFEA); sex hormones; metabolic and inflammatory markers. RESULTS: The mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score - 3.3), trabecular (-2.93), and cortical vBMD (-1.87), and Failure Load by µFEA (-2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (ß = 0.77, p = 0.02), thickness (ß = 0.52, p = 0.04) and number (ß = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (ß = 0.59, p = 0.01), trabecular thickness (ß = 0.43, p = 0.04), cortical thickness (ß = 0.63, p = 0.01) and cortical porosity (ß = 0.74 p = 0.04). CONCLUSIONS: Radius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading. CLINICALTRIALS: gov registration #: (NCT03576001).

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Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

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OBJECTIVE: Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs. STUDY DESIGN: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023. MAIN OUTCOME MEASURE: Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts"). RESULTS: Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046). CONCLUSION: Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843.

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El hueso es un tejido dinámico, que se encuentra en constante adaptación durante la vida de los vertebrados con el fin de alcanzar tamaño, forma, preservar la integridad estructural del esqueleto y regular la homeostasis mineral. Su desarrollo durante la infancia es determinante para alcanzar la estatura, así como la resistencia a fracturas en edad avanzada. Las hormonas sexuales juegan un papel importante en el remodelado óseo, tanto en hombres como en mujeres y las alteraciones en los perfiles hormonales pueden conducir al desarrollo de enfermedades asociadas con el metabolismo del hueso. En mujeres, la deficiencia de estrógenos durante la menopausia es una de las principales causas de osteoporosis, mientras que en hombres los andrógenos pueden influir en la salud ósea al unirse directamente a los receptores de andrógenos o indirectamente a receptores de estrógenos. En esta revisión se explora el papel y los efectos de las hormonas sexuales sobre el metabolismo óseo, las vías de señalización implicadas y los efectos que pueden conducir al desarrollo de enfermedades como la osteoporosis. (AU)

Bone is a dynamic tissue that undergoes constant adaptation throughout the life of vertebrates to achieve size, shape, preserve the structural integrity of the skeleton, and regulate mineral homeostasis. Bone growth during childhood is crucial to achieve height and resistance to fractures later in life. Sex hormones play a key role in bone remodeling in men and women alike, and changes to hormonal profiles can trigger bone metabolism-related diseases. In women, estrogen deficiency during menopause is one of the leading causes of osteoporosis, while in men, androgens can have an impact on bone health by binding directly to androgen receptors or indirectly to estrogen receptors. This review explores the role and effects of sex hormones on bone metabolism, the signaling pathways involved, and the effects that can trigger diseases such as osteoporosis. (AU)

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OBJECTIVE: To identify key research gaps regarding medication therapy to prevent osteoporotic fractures in men. DATA SOURCES: Articles from the peer-reviewed literature containing empirical studies of the use of medication therapy for fracture prevention in men, either in clinical trials or observational studies. STUDY SELECTION AND DATA EXTRACTION: We searched PubMed with search terms including "osteoporosis AND medication therapy management". We read all articles to ensure that they were indeed empirical studies of our topic. For each included study, we searched for all articles in the bibliography, all articles that cited the article, and all related articles, using these functions in PubMed. DATA SYNTHESIS: We have identified six research gaps that could inform the more rational, evidence-based treatment of male osteoporosis. Specifically, among men, we lack key information about: (1) whether treatment can prevent clinical fractures, (2) rates of side effects and complications of therapy, (3) the role of testosterone in treatment, (4) the comparative effectiveness of different therapeutic regimens, (5) role of drug holidays for those receiving bisphosphonates and sequential therapies, and (6) effectiveness of therapy for secondary prevention. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Addressing these six topics should be key goal for the next decade of research on male osteoporosis.

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Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.

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Background: Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). Methods: An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. Results: In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = <0.001). Only 12% of elderly men had normal bone mineral density score. Serum testosterone, chronic obstructive pulmonary disease (COPD) and benign prostatic hypertrophy (BPH) were significantly associated with male osteoporosis with a p-value of 0.019, 0.016 and 0.010, respectively. Vitamin D levels, type 2 diabetes mellitus, hypertension and coronary artery disease did not show any significant association with male osteoporosis. Conclusion: Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures.

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Besides important metabolic repercussions, iron overload is reported to be associated with deleterious effects on articulations and bones. We present the case of a male patient diagnosed with severe osteoporosis and vertebral fracture, in whom the evaluation for secondary osteoporosis revealed hereditary hemochromatosis.

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Men with distal forearm fractures have reduced bone density, an increased risk of osteoporosis and of further fractures. The aim of the study was to investigate the structural determinants of these observations using quantitative CT (qCT). Ninety six men with low-trauma distal forearm fracture and 101 age-matched healthy control subjects were recruited. All subjects underwent a quantitative CT on a standard 64-slice whole body CT scanner. These were analysed on Mindways QCT PRO™ Software to generate volumetric and geometric data at the lumbar spine, femoral neck and total hip, ultra-distal and distal 33 % radius. Biochemical investigations, health questionnaires and measurements of bone turnover were made. Men with fracture had significantly lower total and trabecular vBMD at all sites. The greatest percentage reduction was at the ultra-distal radius (13.5 % total and 11.7 % trabecular vBMD). In the fracture group cortical vBMD was significantly higher in the femoral neck (p < 0.001) and maintained at the ultra-distal radius compared with control subjects. However, cortical cross-sectional area (CSA) and thickness were significantly reduced at the femoral neck (p < 0.001 and p = 0.002 respectively) and forearm sites (CSA ultradistal radius p = 0.001, cortical thickness p = 0.002, CSA distal one third radius p = 0.045 and cortical thickness p = 0.005). Cross sectional moment of inertia (CSMI) and section moduli were significantly reduced at the femoral neck (CSMI1 p = 0.002, CSMI2 p = 0.012 and section moduli Z1 p < 0.001, Z2 p = 0.004) and the ultra-distal radius (CSMI1 p = 0.008 and section moduli Z1 p = 0.018, Z2 p = 0.007). In stepwise logistic regression analysis distal forearm fracture showed the strongest association with a model comprising ultra-distal forearm trabecular vBMD (negative), procollagen type I N-terminal propeptide (PINP, positive) and sex hormone binding globulin (SHBG, negative). In conclusion, these observations explain the structural reasons for the increased fracture risk in men with distal forearm fractures.

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Objective: Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism, but results of human studies mainly conducted in females are controversial. The present study aims to investigate the possible role of FSH excess in male bone health, by comparing for the first time primary and central hypogonadism. Design and Methods: 119 men were enrolled in this cross-sectional observational study at the time of the first diagnosis of hypogonadism. All participants had spontaneous pubertal development. Regarding patients with hypergonadotropic hypogonadism (Hyper-H), Klinefelter syndrome (KS) patients were distinguished from the other forms (non-KS-Hyper-H) based on the onset of FSH elevation. Bone mineral density (BMD) at both lumbar spine (LS) and femoral neck (FN), as well as the prevalence of morphometric vertebral fractures (VFx), were assessed. Results: Across the whole cohort, higher LS and FN BMD were associated with older age at diagnosis and higher body mass index (BMI), respectively. After adjusting for potential confounders (age at diagnosis, BMI, smoking habits, degree of hypogonadism defined by calculated free testosterone, and 25OH vitamin D levels), non-KS-Hyper-H patients showed significantly lower LS BMD and tended to show lower FN BMD values, as compared to those with hypogonadotropic hypogonadism (Hypo-H). In KS men, LS BMD was significantly lower than in those with non-KS-Hyper-H. No significant differences in the prevalence of VFx were found between the groups. Conclusions: These findings suggest a potential negative effect of FSH excess on the male bone mass, especially at spine. The duration of high FSH levels may also contribute to these findings.

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Osteoporosis is often accompanied by bone loss with fat accumulation of the red marrow. A novel technique for quantification of iron and fat content by MRI IDEAL-IQ can visualize hematopoietic areas and fatty deposits in bone marrow; however, the relationship between these indices and total hip bone mineral density (BMD) remains unclear. In this study, the proximal femur of 104 men who underwent pelvic MRI and bone densitometry prior to treatment for non-metastatic prostate cancer was retrospectively examined to investigate the R2* value to quantify iron and proton density fat fraction (PDFF) to assess bone marrow fat content. R2* was significantly positively correlated with BMD (r = 0.6017, p < 0.0001), and PDFF was not correlated with BMD (r = -0.1302, p = 0.0512). Patients with BMD T-score ≤ -2.5 had significantly lower R2* than patients with BMD T-score > -2.5; however, there was no significant difference in PDFF. In the ROC analysis, which examined the predictive ability of R2* with BMD T-score ≤ -2.5 as an outcome, the cut-off value of R2* was 50.7 s-1 (AUC 0.817). These results show R2* correlated with BMD. R2* may be a non-invasive surrogate marker for diagnosing male osteoporosis.

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Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men.

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A total of 277 Hong Kong Chinese men participated in this prospective cohort study. Their osteoporosis knowledge was average. Their perceived susceptibility to osteoporosis was low. Barriers to lifestyle modifications were the strongest predictor for self-efficacy in adopting these activities. These results are useful for planning osteoporosis public awareness campaigns for men. PURPOSE: Male osteoporosis had long been neglected despite one-third of fractures occurring in men. Lifestyle modification through education is the main tactic in osteoporosis prevention, but current programs and strategies are designed for postmenopausal women. Understanding men's knowledge, health belief, and self-efficacy in adopting osteoporosis prevention strategies can help to design a specific program for men. METHODS: A prospective cohort study was conducted in three men's health clinics in Hong Kong from September to October 2020, recruiting 277 men aged ≥ 20 years. They completed a questionnaire consisting of sociodemographic data, 14 general questions from the Facts on Osteoporosis Quiz (FOOQ), Male Osteoporosis Knowledge Quiz (MOKQ), Osteoporosis Health Belief Scale (OHBS), and Osteoporosis Self-Efficacy Scale (OSES). Scores from these scales and their association with sociodemographic data were reported. Correlations between age, knowledge, health beliefs, and self-efficacy were studied using the Health Belief Model. RESULTS: The mean age was 36.4 years old, and 52% had university education. Their mean FOOQ + MOKQ score was 10.8 out of 20; mean OHBS score was 129.2 out of 210; and mean OSE-Exercise and OSE-Calcium scores were 66.4 and 68.9 out of 100 respectively. Self-efficacy of exercise was correlated with young age, perceived exercise benefits, and little barriers to exercise (p < 0.01). Self-efficacy of calcium intake was positively correlated with health motivation and self-efficacy of exercise and negatively correlated with barriers to calcium intake (p < 0.01). CONCLUSION: Male osteoporosis awareness programs should focus on improving knowledge, enhancing awareness on susceptibility, promoting benefits of lifestyle modification, and helping men overcome perceived barriers.

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Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) therapy. Its use is associated with a loss of bone mineral density (BMD) and a greater risk of falls and osteoporotic fractures. In this prospective cohort study, we examined the impact of ADT on muscle and bone strength in men initiating ADT for PCa. Participants were evaluated at three time points: immediately before (week 0), and 6 and 24 weeks after ADT initiation. Study measures included fasting blood levels (for markers of muscle and bone metabolic activity), MRI and QCT imaging (for muscle fat content, and bone density and architecture), and validated clinical tests of muscle strength and gait. Sixteen men completed all study visits. At baseline and throughout the study, participants exercised a median of four times/week, but still experienced weight gain (+2.0 kg at week 24 versus week 0, p = 0.004). Biochemically, all men sustained dramatic early and persistent reductions in sex hormones post-ADT, along with a progressive and significant increase in serum C-telopeptide of type I collagen (CTX, +84% at week 24 versus week 0). There was a trend for rise in serum sclerostin (p = 0.09) and interleukin 6 (IL-6) (p = 0.08), but no significant change in serum myostatin (p = 0.99). Volumetric BMD by QCT declined significantly at the femoral neck (-3.7% at week 24 versus week 0), particularly at the trabecular compartment. On MRI, there were no significant changes in thigh muscle fat fraction. On physical testing, men developed weaker grip strength, but experienced no worsening in lower extremity and lumbar spine muscle strength, or on functional tests of gait. In conclusion, in physically active men, ADT for 24 weeks results in a significant increase in bone resorption and reduction in BMD, but nonsignificant changes in thigh muscle quality (on imaging) or strength and gait (on functional testing). © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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In October 2020, Chinese Society of Osteoporosis and Bone Mineral Research issued the Guidelines for Diagnosis and Treatment of Male Osteoporosis. Taken together with the Guideline for Diagnosis and Treatment of Primary Osteoporosis (2017), this article interprets guideline for male osteoporosis from the aspects of osteoporosis epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, and treatment.

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OBJECTIVE: The primary purpose of this cross-sectional study was to investigate the characteristics of age-related changes in bone microstructure on high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) on dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers in men. The secondary purpose of this study was to examine how bone microstructure is related to aBMD and biochemical markers. METHODS: The subjects were 128 healthy Japanese men (20-97 years old). Bone microstructure was measured in the distal radius and tibia using second-generation HR-pQCT; aBMD in the proximal femur and lumbar spine was measured with DXA; and tartrate-resistant acid phosphatase-5b (TRACP-5b), type I procollagen-N-propeptide (P1NP), 25(OH) vitamin D, and pentosidine concentrations were measured by blood tests. RESULTS: In trabecular bone, the trabecular volumetric BMD (Tb.vBMD) and trabecular number (Tb.N) were lower with age (r = -0.23, -0.35) (r = -0.36,-0.33), and trabecular separation (Tb.Sp) and the star volume of marrow space (V*ms) were higher with age (r = 0.29, 0.41) (r = 0.34, 0.38) in both the radius and tibia. In cortical bone, cortical volumetric BMD (Ct.vBMD) was lower with age (r = -0.25, -0.52), and cortical porosity (Ct.Po) was higher with age (r = 0.67, 0.62) in both the radius and tibia. In the tibia, cortical thickness (Ct.Th) and cortical area (Ct.Ar) were lower with age (r = -0.40) (r = -0.43), whereas, in the radius, they were maintained, and periosteal perimeter (Ct.Pm) was higher with age (r = 0.35). aBMD in the proximal femur and P1NP were lower, and pentosidine was higher with increased age, whereas aBMD in the lumbar spine, TRACP-5b, and 25(OH) vitamin D had no relationships with age. DXA and HR-pQCT showed strong correlations particularly with femoral aBMD and tibial Tb.vBMD and Ct.Ar (r = 0.61) (r = 0.61), whereas no DXA parameters were related with Ct.Po. In correlations between biochemical markers and HR-pQCT, TRACP-5b and total P1NP were negatively correlated with Ct.vBMD (r = -0.31) (r = -0.35), but almost no other correlations were seen. CONCLUSIONS: Age-related changes of the bone microstructure in men were characterized by decreases in trabecular and cortical vBMD associated with decreased trabecular number, cavitation of the trabecular structure, and increased cortical porosity. Femoral aBMD was strongly related to bone microstructure in the tibia, whereas both lumbar aBMD and femoral aBMD were not related to Ct.Po, and biochemical markers showed almost no relationships with bone microstructure.

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BACKGROUND: Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. METHODS: The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. RESULTS: A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. CONCLUSIONS: The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.

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In the present observational cohort study in 4902 men and 9804 women, we found that the factors associated with osteoporosis care utilization in men were comorbidities, adjuvant hormonal therapy for prostate cancer, vertebral or hip fractures, and glucocorticoid treatment. INTRODUCTION: Male osteoporosis is associated with an important clinical and economic burden worldwide; nevertheless, undertreatment of men with osteoporosis is common. Understanding the factors associated with referral to bone specialists may help to define future interventions to improve access to osteoporosis care for male patients. METHODS: We conducted a retrospective analysis of a nationwide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk by considering clinical and densitometric risk factors, including the presence of prior hip or vertebral and non-vertebral or non-hip fractures. We compared the clinical characteristics of male individuals with an age-matched cohort of women. Propensity score generation with a 2:1 female-to-male ratio was performed using a logistic regression model to age-match the cohorts. RESULTS: We analyzed a sample of 4902 men at high risk for osteoporosis. We found that the factors associated with osteoporosis care utilization in men were the presence of comorbidities (OR 1.939, 95% CI 1.799-2.090), adjuvant hormonal therapy for prostate cancer (OR 1.482, 95% CI 1.315-1.670), the presence of vertebral or hip fractures (OR 1.490, 95% CI 1.378-1.611), and glucocorticoid treatment (OR 2.573, 95% CI 2.274-2.832). CONCLUSIONS: Men are more commonly referred to the bone specialist with a prevalent fragility fracture and/or diagnosis of secondary osteoporosis as compared with women. Our study suggests that there is a lack of screening for the primary prevention of osteoporosis in men as compared with that in women.

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Osteoporotic fractures of the vertebrae and the proximal end of the femur dramatically impair quality of life and increase morbidity and mortality. Although up to 40% of all osteoporotic fractures occur in men, physicians tend to underestimate the osteoporosis in men, and it remains underdiagnosed and undertreated. Though, there is no evidence that current approved osteoporosis medications work any less well in men than in women, insufficient awareness of the risk of fractures, fear of side effects of drugs and other barriers have made management challenging in men at risk for fracture. Our review provides updates on pathophysiology and current options for diagnosis and treatment of male osteoporosis.

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