Fractures In Postmenopausal Women Research Articles

Effects of romosozumab on bone mineral density and fractures in postmenopausal women: a meta-analysis

Purpose: Romosozumab, a mono-clonal antibody has been approved for the treatment of postmenopausal women with osteoporosis and high fracture risk. This meta-analysis evaluated the effect of romosozumab on Bone Mineral Density (BMD) and fracture occurrence in postmenopausal women with osteoporosis.Methods: A systematic search was done adhered to the PRISMA guidelines in PubMed, Ovid and Clinicaltrials.gov and eligible studies were selected. The details related to study participants, changes in BMD at the lumber spine (LS), total hip (TH) and femoral neck (FN) and the occurrence of fractures during the period were extracted. The mean differences of BMDs between the two groups and odds ratios (OR) of fractures were considered as the outcome of the studies.Results: Of the 11 potentially eligible articles, only four studies fulfilled the selection criteria and they were included in the final analysis. Romosozumab therapy for 12 months increased mean BMD at the LS by 12.7% (95% CI, 9.7, 15.6), TH by 4.8% (95% CI, 3.3,6.3) and FN by 4.1% (95% CI, 3.1, 5.2). Treatment with romosozumab decreased the odds of new vertebral fractures and vertebral fractures by 58% (OR=0.42, CI, 0.23,0.91) and 25% (OR=0.75, CI, 0.53,1.06) respectively at the end of 12 months.Conclusion: Romosozumab significantly increases BMD at LS, TH and FN and reduces the risk of new vertebral and non-vertebral fractures in postmenopausal women with osteoporosis.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

A practical approach for anabolic treatment of bone fragility with romosozumab.

Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management. The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures. Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent. Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

Association between reduced physical activity and 10-years risk of fracture in postmenopausal women with osteopenia/osteoporosis

Association between reduced physical activity and 10-years risk of fracture in postmenopausal women with osteopenia/osteoporosis

P043 The different roles of FRAX risk factors as predictors of fragility fractures in peri-menopausal vs post-menopausal patients: results from a large population-based cohort study

Abstract Background/Aims The marked rise in the prevalence of fragility fractures affecting both women undergoing the transition to menopause (i.e. peri-menopause), and post-menopausal women, confers a significant burden on patients’ health and quality of life. The risk factors for fractures in post-menopausal women have been previously well-explored, and tend to align with the FRAX variables. However, there is less consensus regarding the fracture risk factors in peri-menopausal women. We compare the association between FRAX risk factors and fractures across peri-menopausal and post-menopausal women, selected from the same large population-based cohort. Methods Female patients referred for a DXA scan at the Royal Lancaster Infirmary between 2004-2011 provided information relating to any previous fragility fracture(s), FRAX risk factors, and menopause status (i.e. not post-menopausal vs post-menopausal) through a questionnaire. Patients aged 41 to 51 (median menopause age in UK) who had not undergone the menopause, as per their questionnaire response, were categorised as ‘peri-menopausal’. Logistic regression modelling, which included adjustment for potential confounders, was performed using r(version 4.3.1). Results Our study included 23388 patients, including 3785 peri-menopausal patients and 20774 post-menopausal patients, with a mean age of 47.5 (SD:3.0) and 66.1 (SD:10.4) respectively. The prevalence of fragility fractures was greater in the post-menopausal than peri-menopausal cohort (42.8% vs 25.5% respectively; p &amp;lt; 0.001). Across post-menopausal patients, following adjustment for the other FRAX risk factors, significant predictors of increased fracture risk were age (odds ratio (OR): 1.04 (95% CI:1.03-1.04, p &amp;lt; 0.001), smoking (OR:1.16 (CI:1.09-1.23, p &amp;lt; 0.001), alcohol (OR:1.54, CI:1.36-1.74, p &amp;lt; 0.001), and a family history of fracture(s) (OR:1.21 (CI:1.13-1.29, p &amp;lt; 0.001). Comparatively, across peri-menopausal patients, only alcohol (OR:1.57, CI:1.08-2.26, p = 0.016) and smoking (OR:1.22 (CI:1.00-1.48, p = 0.045) positively predicted fracture risk. Corticosteroid use was associated with a reduced fracture risk across both post-menopausal (OR:0.84, CI:0.79-0.90, p &amp;lt; 0.001) and peri-menopausal (OR:0.79, CI: 0.64-0.97, p = 0.024) cohorts. Conclusion Different FRAX risk factors predict fracture occurrence across post-menopausal and peri-menopausal patients; notably, only smoking and alcohol consumption predict an increased fracture risk in the latter group. Interestingly, corticosteroids were associated with a reduced risk of fractures across both groups. This finding may be elucidated by the fact that low-dose corticosteroids can exert an anti-inflammatory effect, and may protect bone cells. However, our finding is limited by the fact that the indication, dose and duration of corticosteroids were unknown. More generally, our study is limited by the fact that patients’ peri-menopausal status was not clinically confirmed, but inferred based on patients’ age and self-reported menopause status. Our results suggest that the FRAX risk factors, which were derived from analysis of predominantly 50-80 year old patients, may require adjustment for peri-menopausal patients (many of whom are aged &amp;lt;50). Future studies should assess whether our conclusions apply to specific fracture sites, and are replicated across more demographically diverse patient populations. Disclosure K. Song: None. M. Bukhari: None.

Osteoporotic quality of life, self-efficacy, and fracture protection behaviors in postmenopausal women

SummaryIt is important for postmenopausal women to acquire bone health protective behaviors to protect them from fractures. For this reason, it is necessary to evaluate bone health during menopause and to inform women.PurposeThis study was conducted to examine osteoporotic fracture protection behaviors, quality of life, and self-efficacy in postmenopausal women.MethodsIn the study, the data were evaluated with the socio-demographic data form, Osteoporotic Fracture Protection Scale, Osteoporosis Self-Efficacy-Efficacy Scale, European Osteoporosis Foundation Quality of Life Questionnaire-41, which includes introductory information on socio-demographic characteristics.ResultsIt was determined that the postmenopausal women included in our study were between the ages of 45–92; more than half of them had chronic diseases; their average BMI was 29; and their DEXA score was − 3.00 ± 0.41. Among the people included in our study, those with a history of fractures had lower self-efficacy scores. It was determined that the fracture prevention scale scores of the participants were above the average, and the average of the osteoporosis-related quality of life score was high. In addition, it was determined that there was a strong positive correlation between self-efficacy and fracture prevention scale.ConclusionIt is important to determine behaviors to prevent osteoporotic fractures in postmenopausal women, to raise the necessary awareness and to inform patients about the precautions to be taken. It is thought that it will increase patients’ quality of life by increasing their disease-related self-efficacy. Therefore, there is a need for research on providing education to op patients and examining the results.

Summary of the 2023 Thai Menopause Society Clinical Practice Guideline on Menopausal Hormone Therapy.

The Thai Menopause Society is an academic organization consisting of healthcare professionals engaged in menopause medicine. The position statement was first issued in 1994 and updated in 2003 and 2023. Herein, we reviewed the important updates of the 2023 position statement on menopausal hormone therapy (MHT) as an international reference for healthcare professionals in Thailand. An advisory panel of clinicians and research experts in the field of menopause reviewed the recommendation of published International Consensus Statements and updated the evidence using the MEDLINE database through PubMed. The evidence-based information and relevant publications were assessed, and a consensus on recommendations was subsequently achieved using the level of evidence to determine the recommendation strength and evidence quality. MHT remains the most effective treatment for vasomotor symptoms and genitourinary syndromes of menopause even after 20 years. Additionally, it is effective in preventing bone loss and fractures in postmenopausal women. The cardiovascular risk of MHT increased in women who initiated MHT after 60 years of age. Hormone therapy should be individualized following the hormone type, dose, administration route, use duration, and progestogen inclusion. The necessary pretreatment evaluation and appropriate follow-up recommendations were added for improved MHT standard care. The updated 2023 Clinical Practice Guideline on MHT is useful for gynecologists, general physicians, endocrinologists, and other healthcare professionals in treating menopausal women receiving hormone therapy in Thailand.

Evaluation of Bone Density Changes Before and After One Year of Denosumab (Prolia) Administration in Osteoporosis Patients

Background: Osteoporosis, a widespread disease associated with aging, is characterized by a decrease in bone tissue density. With the global population aging, numerous studies aim to present methods for preventing or treating this disease to avoid pathological fractures by preserving bone density. Objectives: This study aimed to compare the changes in bone density in females with osteoporosis before and after receiving denosumab for at least one year. Methods: This clinical trial was conducted on 202 patients with osteoporosis who were referred to two private clinics in Tehran between 2019 and 2020. Each patient received two subcutaneous injections of 60 mg denosumab (Prolia) once every six months. Bone density was measured using the DXA method, and the T-score and the risk of bone fracture were calculated and compared using the FRAX instrument before drug administration and six months after the second dose injection. Results: The average age of the participants was 69.0 ± 8.0 years. Significant differences were observed in vertebral bone density (-2.55 ± 0.06 to -2.00 ± 0.07) and femur bone density (-2.10 ± 0.10 to -1.88 ± 0.06) before and after denosumab treatment (P &lt; 0.05). Furthermore, the risk of major fractures (23.0 ± 1.9 to 18.9 ± 1.5) and hip fractures (8.5 ± 1.3 to 5.7 ± 0.9) significantly decreased before and after treatment with denosumab (P &lt; 0.05). A significant improvement in bone density was observed across all age groups of patients before and after treatment with denosumab (P &lt; 0.05). Conclusions: Denosumab significantly reduces the risk of bone fractures and enhances bone density in postmenopausal women. It proves to be an effective medication for reducing the increased risk of fractures in postmenopausal women and for improving their bone density.

Physical function trajectory after wrist or lower arm fracture in postmenopausal women: results from the Women’s Health Initiative Study

SummaryLong-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older.IntroductionPhysical functioning trajectory following lower arm or wrist fracture is not well understood.PurposeThis study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age.MethodsWe performed a nested case–control study of prospective data from the Women’s Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining.ResultsMean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19–1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29–1.88); age 70–79 years aOR 1.29 (95% CI 1.09–1.52); age < 70 years aOR 1.15 (95% CI 0.86–1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level.ConclusionsWomen with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.

Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women

Previous research has found that vegetarian diets are associated with lower bone mineral density and higher risk of fractures, but these studies did not differentiate the quality of the plant-based foods. To examine the association between the quality of plant-based diets (not necessarily vegan but also omnivorous) and hip fracture risk among postmenopausal women in the Nurses' Health Study. This cohort study analyzed data from 70 285 postmenopausal women who participated in the US Nurses' Health Study from 1984 through 2014. Data were analyzed from January 1 to July 31, 2023. Hip fractures were self-reported on biennial questionnaires. Diet was assessed every 4 years using a validated semiquantitative food frequency questionnaire. Plant-based diet quality was assessed using 2 previously established indices: the healthful Plant-Based Diet Index (hPDI), for which healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee) received positive scores, whereas less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, and sweets or desserts) and animal foods received reversed scores; and the unhealthful Plant-Based Diet Index (uPDI), for which positive scores were given to less healthy plant foods and reversed scores to healthy plant and animal foods. Quintile scores of 18 food groups were summed, with a theoretical range for both indices of 18 to 90 (highest adherence). Cox proportional hazards regression with time-varying covariates was used to compute hazard ratios (HRs) and 95% CIs for hip fracture. In total, 70 285 participants (mean [SD] age, 54.92 [4.48] years; 100% White women) were included, and 2038 cases of hip fracture were ascertained during the study and for up to 30 years of follow-up. Neither the hPDI (HR for highest vs lowest quintile, 0.97 [95% CI, 0.83-1.14]) nor the uPDI (HR for highest vs lowest quintile, 1.02 [95% CI, 0.87-1.20]) for long-term diet adherence was associated with hip fracture risk. However, when examining recent intake for the highest vs lowest quintiles, the hPDI was associated with 21% lower risk of hip fracture (HR, 0.79 [95% CI, 0.68-0.92]; P = .02 for trend), and the uPDI was associated with 28% higher risk (1.28 [95% CI, 1.09-1.51]; P = .008 for trend). Findings of this cohort study indicated that long-term adherence to healthful or unhealthful plant-based diets as assessed by hPDI and uPDI scores was not associated with hip fracture risk. Future research should clarify whether the associations observed with recent dietary intake are due to short-term effects of these dietary patterns, reverse causality, or both.

Comparative Study of Serum Calcium Level Between Postmenopausal and Premenopausal Women

In postmenopausal women, more significant bony consequences are associated with low blood calcium levels. A observational cross-sectional study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka from July 2014 to June 2015. Serum calcium levels were compared between postmenopausal women as cases and premenopausal women as controls. The study sample size was 100 of which 50 were postmenopausal, and 50 were premenopausal. Mean (±SD) of serum calcium level was significantly higher in the premenopausal group than in the postmenopausal group. Serum calcium level was 8.66±0.43 mg/dL in postmenopausal women and 9.12±0.59mg/dL in premenopausal women. Both the values were within the normal reference range, but the difference was statistically significant with a p-value of 0.001. By this research work, it is observed that postmenopausal women are more prone to develop osteoporosis with a decreased serum calcium concentration. Routine check-up of this biochemical parameter may provide valuable information for preventing osteoporotic fractures in postmenopausal women.&#x0D; Bangladesh J Med Biochem 2019; 12(1): 1-5

Spinal osteoarthritis is a risk of vertebral fractures in postmenopausal women

Recent studies have revealed that despite high bone mineral density (BMD), osteoarthritis (OA) is a risk factor for osteoporotic fractures. However, the relationship between spinal OA and vertebral fractures has not yet been fully investigated. This longitudinal analysis used a subset of ongoing cohort study consist with Japanese postmenopausal women. The prevalence of spinal OA was determined using Kellgren–Lawrence grading method. The incidence of vertebral fractures were determined by semiquantitative analysis of spinal X-ray films. The relationship between the presence of spinal OA and incidence of vertebral fractures was evaluated using the Cox regression analysis. In total, 1480 women were followed up for 8.1 ± 6.4 years. Among them, 923 were diagnosed with spinal OA, and incident vertebral fractures were observed in 473 participants. After adjusting for confounding variables, the spinal OA (≥ grade 2) was a significant predictor of incident vertebral fractures (hazard ratio, 1.52; 95% confidence interval: 1.19–1.93, p = 0.001). Using ROC analysis, the thresholds of lumbar BMD for incident vertebral fractures were 0.952 g/cm2 for patients with spinal OA and 0.753 g/cm2 for patients without spinal OA. The presence of spinal OA is a risk factor for incident vertebral fractures despite high lumbar BMD.

Association between Postmenopausal Osteoporosis and IL-6、TNF-α: A Systematic Review and A Meta-analysis.

Postmenopausal osteoporosis (PMOP) greatly increases the risk of bone fracture in postmenopausal women, seriously affects the quality of life of patients, and is an important global public health problem. Persistent chronic systemic inflammation may be involved in the change process of PMOP, and many cytokines, such as TNF-alpha and Interleukin-6, play an important role in the inflammatory response. Therefore, This study takes commonly representative inflammatory factors as indicators to better determine their role in PMOP patients by means of databases from multiple studies for use in Meta-analysis. Systematic review of studies on the relationship between PMOP and markers of inflammation: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Each effect size was expressed with a 95% confidence interval (CI), and I2 quantified the heterogeneity. The final results were aggregated and evaluated using random or fixed effects models. Twenty-one original studies were identified. There were twenty studies involving IL-6 and eleven involving TNF-α. Overall, The levels of IL-6[MD=23.93, 95%CI (19.65, 28.21)] and TNF-α[MD=2.9, 95%CI (2.37, 3.44)] were increased in PMOP patients compared with postmenopausal women without osteoporosis; The levels of IL-6[MD=42.4, 95%CI (38.62, 46.19)] and TNF-α[MD=0.40, 95%CI (0.36, 0.44)] were significantly higher than those of premenopausal healthy women. The levels of inflammatory cytokines IL-6 and TNF-α were significantly increased in PMOP patients compared with controls, suggesting that persistent chronic inflammatory reaction exists in PMOP patients, which may be an important cause of aggravated osteoporosis in postmenopausal women. Therefore, the level of IL-6 and TNF-α indexes may be of great significance for the early prevention, diagnosis, treatment and prognosis assessment of PMOP.

Obesity Variants in the GIPR Gene Are not Associated With Risk of Fracture or Bone Mineral Density.

It is not clear if antagonizing the GIP (glucose-dependent insulinotropic polypeptide) receptor (GIPR) for treatment of obesity is likely to increase the risk of fractures, or to lower bone mineral density (BMD) beyond what is expected with rapid weight loss. The objective of this study was to investigate the risk of fracture and BMD of sequence variants in GIPR that reduce the activity of the GIP receptor and have been associated with reduced body mass index (BMI). We analyzed the association of 3 missense variants in GIPR, a common variant, rs1800437 (p.Glu354Gln), and 2 rare variants, rs139215588 (p.Arg190Gln) and rs143430880 (p.Glu288Gly), as well as a burden of predicted loss-of-function (LoF) variants with risk of fracture and with BMD in a large meta-analysis of up to 1.2 million participants. We analyzed associations with fractures at different skeletal sites in the general population: any fractures, hip fractures, vertebral fractures and forearm fractures, and specifically nonvertebral and osteoporotic fractures in postmenopausal women. We also evaluated associations with BMD at the lumbar spine, femoral neck, and total body measured with dual-energy x-ray absorptiometry (DXA), and with BMD estimated from heel ultrasound (eBMD). None of the 3 missense variants in GIPR was significantly associated with increased risk of fractures or with lower BMD. Burden of LoF variants in GIPR was not associated with fractures or with BMD measured with clinically validated DXA, but was associated with eBMD. Missense variants in GIPR, or burden of LoF variants in the gene, are not associated with risk of fractures or with lower BMD.

The Role of Irisin throughout Women's Life Span.

Since its discovery, much attention has been drawn to irisin's potential role in metabolic and reproductive diseases. This narrative review summarizes and updates the possible role played by this fascinating molecule in different physiological (puberty and menopause) and pathological (polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), endometriosis, and gestational diabetes) conditions that can affect women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic-pituitary-gonadal axis activation, and appears to play a role in the timing of puberty onset. Serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in PCOS is still controversial, although an "irisin resistance" mechanism has been hypothesized. In addition to its impact on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with FHA. In clinical settings, further controlled, prospective and randomized clinical trials are needed to investigate the casual relationship between irisin levels and the conditions described and, in turn, to establish the role of irisin as a prognostic/diagnostic biomarker or a therapeutic target.

Relationship between menopausal hormone therapy and incidence of fractures in postmenopausal women

Objective Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. Method This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen–progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. Results EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50–59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. Conclusion In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT.

Identification of a potential signature to predict the risk of postmenopausal osteoporosis

BackgroundPostmenopausal osteoporosis (PMOP) is related to the elevated risk of fracture in postmenopausal women. Thus, to effectively predict the occurrence of PMOP, we explored a novel gene signature for the prediction of PMOP risk. MethodsThe WGCNA analysis was conducted to identify the PMOP-related gene modules based on the data from GEO database (GSE56116 and GSE100609). The “limma” R package was applied for screening differentially expressed genes (DEGs) based on the data from GSE100609 dataset. Next, LASSO Cox algorithm were applied to identify valuable PMOP-related risk genes and construct a risk score model. GSEA was then conducted to analyze potential signaling pathways between high-risk (HR) score and low-risk (LR) score groups. ResultsA novel risk model with five PMOP-related risk genes (SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1) was developed for predicting PMOP risk status. RT-qPCR and western blot assays validated that compared to postmenopausal non-osteoporosis (non-PMOP) patients, SCUBE3, ULBP1, SEPT12 levels were obviously elevated, and TNNC1 and SPON1 levels were reduced in blood samples from PMOP patients. Additionally, PMOP-related pathways such as MAPK signaling pathway, PI3K-Akt signaling pathway and HIF-1 signaling pathway were significantly activated in the HR-score group compared to the LR-score group. The circRNA-gene-miRNA and gene-transcription factor networks showed that 533 miRNAs, 13 circRNAs and 40 TFs might be involved in regulating the expression level of these five PMOP-related genes. ConclusionCollectively, we developed a PMOP-related gene signature based on SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1 genes, and higher risk score indicated higher risk suffering from PMOP.

Triglyceride Glucose Index is Strongly Associated with a Fragility Fracture in Postmenopausal Elderly Females with Type 2 Diabetes Mellitus Combined with Osteoporosis: A 6-Year Follow-Up Study.

The triglyceride glucose (TyG) index serves as an indicator of insulin resistance (IR), which is also associated with bone metabolism. However, research on the relationship between the TyG index and a fragility fracture in individuals with type 2 diabetes mellitus (T2DM) or osteoporosis (OP) remains sparse. This study aims to explore the association between the TyG index and fragility fracture risk in postmenopausal elderly females with T2DM combined with OP based on an ambispective cohort study. A total of 220 postmenopausal women hospitalized with T2DM combined with OP between January 2015 and December 2020 were eligible for inclusion in this study. All participants were followed up every 6 months for 6 years with a median of 42 months. According to the tertiles of the TyG index, participants were divided into three groups: low-level (≤ 8.79, n =73), moderate-level (8.80-9.32, n=73), and high-level (≥ 9.33, n=74). The association between the TyG index and fragility fracture risk was then assessed. Out of 220 patients, 46 experienced fragility fracture events (20.9%). Multivariate Cox regression analysis showed that the TyG index was positively associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Furthermore, compared to the low-level group, with the TyG index level increase by 1.0, the risk for fragility fracture increased 1.293-fold in the high-level group (HR=2.293, 95% CI=1.007-5.221, P < 0.05). Kaplan-Meier survival analysis indicated that fragility fractures were more likely to occur in patients with high levels of TyG index (log-rank, all P < 0.05). Our study showed that the TyG index was strongly associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Therefore, special attention should be paid to postmenopausal elderly females with T2DM combined with OP in routine clinical practice.