[Bone mineral density in women with rheumatoid arthritis: A link between immune and biochemical markers].

AIM: To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA). MATERIALS AND METHODS: The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (LI-LIV), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D3, myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed. RESULTS: PTH (ß=-0.22, -0.35 and -0.30 for LI-LIV, FN and TH, respectively), CRP (ß=-0.18, 0.23 and -0.22 for LI-LIV, FN and TH, respectively) and leptin (ß=0.35, 0.32 and 0.42 for LI-LIV, FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of LI-LIV and TH (ß=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (ß=-0.21, -0.24, respectively) and IL-6 and BMD of FN (ß=0.37). CONCLUSION: The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.

Early changes of bone metabolites and lymphocyte subsets may participate in osteoporosis onset: a preliminary study of a postmenopausal osteoporosis mouse model.

Purpose: Metabolic and immune changes in the early stages of osteoporosis are not well understood. This study aimed to explore the changes in bone metabolites and bone marrow lymphocyte subsets and their relationship during the osteoporosis onset. Methods: We established OVX and Sham mouse models. After 5, 15, and 40 days, five mice in each group were sacrificed. Humeri were analyzed by microCT. The bone marrow cells of the left femur and tibia were collected for flow cytometry analysis. The right femur and tibia were analyzed by LC-MS/MS for metabolomics analysis. Results: Bone microarchitecture was significantly deteriorated 15 days after OVX surgery. Analysis of bone metabolomics showed that obvious metabolite changes had happened since 5 days after surgery. Lipid metabolism was significant at the early stage of the osteoporosis. The proportion of immature B cells was increased, whereas the proportion of mature B cells was decreased in the OVX group. Metabolites were significantly correlated with the proportion of lymphocyte subsets at the early stage of the osteoporosis. Conclusion: Lipid metabolism was significant at the early stage of the osteoporosis. Bone metabolites may influence bone formation by interfering with bone marrow lymphocyte subsets.

Mechanistic study on the alleviation of postmenopausal osteoporosis by Lactobacillus acidophilus through butyrate-mediated inhibition of osteoclast activity.

In China, traditional medications for osteoporosis have significant side effects, low compliance, and high costs, making it urgent to explore new treatment options. Probiotics have demonstrated superiority in the treatment of various chronic diseases, and the reduction of bone mass in postmenopausal osteoporosis (PMOP) is closely related to the degradation and metabolism of intestinal probiotics. It is crucial to explore the role and molecular mechanisms of probiotics in alleviating PMOP through their metabolites, as well as their therapeutic effects. We aim to identify key probiotics and their metabolites that affect bone loss in PMOP through 16srDNA sequencing combined with non-targeted metabolomics sequencing, and explore the impact and possible mechanisms of key probiotics and their metabolites on the progression of PMOP in the context of osteoporosis caused by estrogen deficiency. The sequencing results showed a significant decrease in Lactobacillus acidophilus and butyrate in PMOP patients. In vivo experiments confirmed that the intervention of L. acidophilus and butyrate significantly inhibited osteoclast formation and bone resorption activity, improved intestinal barrier permeability, suppressed B cells, and the production of RANKL on B cells, effectively reduced systemic bone loss induced by oophorectomy, with butyric acid levels regulated by L. acidophilus. Consistently, in vitro experiments have confirmed that butyrate can directly inhibit the formation of osteoclasts and bone resorption activity. The above research results indicate that there are various pathways through which L. acidophilus inhibits osteoclast formation and bone resorption activity through butyrate. Intervention with L. acidophilus may be a safe and promising treatment strategy for osteoclast related bone diseases, such as PMOP.

Joint effects between cadmium exposure and dietary antioxidant quality score on osteoporosis and bone mineral density.

To explore the relationship between dietary antioxidant quality score (DAQS) and Cd exposure both alone and in combination with osteoporosis and bone mineral density (BMD) among postmenopausal women. In total, 4920 postmenopausal women from the National Health and Nutrition Examination Survey were included in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses to assess the association between DAQS and Cd exposure with femur neck BMD, total femur BMD, osteoporosis among postmenopausal women, respectively, and the coexistence effect of DAQS and Cd exposure. Four hundred and ninety-nine had osteoporosis. DAQS (OR = 0·86, 95 % CI 0·77, 0·97) and high DAQS (OR = 0·60, 95 % CI 0·36, 0·99) were found to be associated with decreased odds of osteoporosis, while Cd exposure (OR = 1·34, 95 % CI 1·04, 1·72) and high Cd exposure (OR = 1·45, 95 % CI 1·02, 2·06) were related to increased odds of osteoporosis. A positive correlation was observed between high DAQS and both total femur BMD and femur neck BMD. Conversely, Cd exposure was found to be negatively correlated with total femur BMD and femur neck BMD. Additionally, taking low-Cd and high-quality DAQS group as reference, the joint effect of Cd exposure and DAQS showed greater increased odds of osteoporosis and decreased total femur BMD and femur neck BMD as Cd level and DAQS combinations worsened. There may be an interaction between Cd exposure and DAQS for femur neck BMD, total femur BMD, and osteoporosis in postmenopausal women.

Low BMI, blood calcium and vitamin D, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Aim: To explore the risk factors of osteoporosis in postmenopausal women in China. Method: This study collected all patient data from January 2014 to December 2015. Basic information and questionnaires were collected from 524 postmenopausal women in Sanya and Hainan Province. The questionnaire was administered to the enrolled participants by endocrinologists. Biochemical parameters were measured using fasting blood samples, and bone density was measured by dual energy X-ray absorptiometry at the department of radiology of Hainan hospital, PLA General Hospital. Participants with an R-value of ≤-2.5 were diagnosed with osteoporosis. After deleting missing values for each factor, 334 participants were divided into the osteoporosis (n=35) and non-osteoporosis (n=299) groups according to the R-values. Results: The participants had a median age of 60.8 years (range: 44-94 years). Among the 334 postmenopausal women included in this study, 35 (10.5%) were diagnosed with osteoporosis. Univariate analysis showed statistically significant differences in age, BMI, type of work, alkaline phosphatase, years of smoking, blood calcium levels, kyphosis, fracture, and asthma between the two groups (P<0.05). In addition, multivariate logistic analysis showed that age (odds ratio [OR]: 1.185, 95% confidence interval [CI]: 1.085-1.293, P<0.001) and kyphosis times (OR:1.468, 95% CI: 1.076-2.001, P=0.015) were positively correlated with postmenopausal osteoporosis, whereas BMI (OR: 0.717, 95% CI: 0.617-0.832, P<0.001), blood calcium levels (OR: 0.920, 95% CI: 0.854-0.991, P=0.027), vitamin D levels (OR: 0.787, 95% CI: 0.674-0.918, P=0.002), and outdoor activity time (OR: 0.556, 95% CI: 0.338-0.915, P=0.021) were negatively correlated with postmenopausal osteoporosis. Conclusion: Low BMI, blood calcium and vitamin D levels, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Higher lacto-vegetarian dietary score is associated with reduced risk of postmenopausal osteoporosis: A case-control study in a sample of Iranian postmenopausal women.

Osteoporosis is a systemic skeletal disease manifesting as weak and fragile bones. Dietary patterns have been described as an affecting constituent of bone metabolism. There is no consensus on the advantages or harms of vegetarian diets on bone health. This study aimed to design a lacto-vegetarian dietary score (LVDS) to evaluate the similarity of an individual's dietary pattern to the lacto-vegetarian dietary pattern and assess its association with postmenopausal osteoporosis (PMO). We hypothesized that individuals with greater LVDS will have a lower risk for PMO. In this hospital-based, case-control study, 220 cases (definitively diagnosed with osteoporosis) and 220 age-matched controls were registered. Usual dietary intakes were evaluated by a validated 147-item semiquantitative food frequency questionnaire. To design the LVDS, the energy-adjusted intakes of 12 food groups were categorized into quintiles, and positive or reverse points were assigned. To determine the association between the LVDS and PMO, binary logistic regression was used. Those in the top tertile of the LVDS had a lower chance of PMO compared with those in the bottom tertile (odds ratio, 0.11; 95% confidence interval, 0.06-0.22). An inverse relation was obtained between vegetables, fruits, legumes, nuts, dairy, soy protein, and egg consumption and PMO. Higher consumption of vegetable and animal oils significantly increased the risk of PMO. A dietary pattern similar to the lacto-vegetarian dietary pattern and concentrated on greater consumption of legumes, nuts, dairy, fruits, vegetables, and soy protein can be suggested as a protective method against PMO. Further, longitudinal studies are required to confirm these findings.

Secoisolariciresinol diglucoside regulates estrogen receptor expression to ameliorate OVX-induced osteoporosis.

OBJECTIVE: Secoisolariciresinol diglucoside (SDG) is a phytoestrogen that has been reported to improve postmenopausal osteoporosis (PMOP) caused by estrogen deficiency. In our work, we aimed to investigate the mechanism of SDG in regulating the expressions of ERs on PMOP model rats. METHODS: Ovariectomization (OVX) was used to establish PMOP model in rats. The experiment was allocated to Sham, OVX, SDG and raloxifene (RLX) groups. After 12-week treatment, micro-CT was used to detect the transverse section of bone. Hematoxylin and Eosin staining and Safranine O-Fast Green staining were supplied to detect the femur pathological morphology of rats. Estradiol (E2), interleukin-6 (IL-6), bone formation and bone catabolism indexes in serum were detected using ELISA. Alkaline phosphatase (ALP) staining was used to detect the osteogenic ability of chondrocytes. Immunohistochemistry and Western blot were applied to detect the protein expressions of estrogen receptors (ERs) in the femur of rats. RESULTS: Compared with the OVX group, micro-CT results showed SDG could lessen the injury of bone and improve femoral parameters, including bone mineral content (BMC) and bone mineral density (BMD). Pathological results showed SDG could reduce pathological injury of femur in OVX rats. Meanwhile, SDG decreased the level of IL-6 and regulated bone formation and bone catabolism indexes. Besides, SDG increased the level of E2 and conversed OVX-induced decreased the expression of ERα and ERß. CONCLUSION: The treatment elicited by SDG in OVX rats was due to the reduction of injury and inflammation and improvement of bone formation index, via regulating the expression of E2 and ERs.

A clinical prediction model for 10-year risk of self-reported osteoporosis diagnosis in pre- and perimenopausal women.

A machine learning model using clinical, laboratory, and imaging data was developed to predict 10-year risk of menopause-related osteoporosis. The resulting predictions, which are sensitive and specific, highlight distinct clinical risk profiles that can be used to identify patients most likely to be diagnosed with osteoporosis. PURPOSE: The aim of this study was to incorporate demographic, metabolic, and imaging risk factors into a model for long-term prediction of self-reported osteoporosis diagnosis. METHODS: This was a secondary analysis of 1685 patients from the longitudinal Study of Women's Health Across the Nation using data collected between 1996 and 2008. Participants were pre- or perimenopausal women between 42 and 52 years of age. A machine learning model was trained using 14 baseline risk factors-age, height, weight, body mass index, waist circumference, race, menopausal status, maternal osteoporosis history, maternal spine fracture history, serum estradiol level, serum dehydroepiandrosterone level, serum thyroid-stimulating hormone level, total spine bone mineral density, and total hip bone mineral density. The self-reported outcome was whether a doctor or other provider had told participants they have osteoporosis or treated them for osteoporosis. RESULTS: At 10-year follow-up, a clinical osteoporosis diagnosis was reported by 113 (6.7%) women. Area under the receiver operating characteristic curve of the model was 0.83 (95% confidence interval, 0.73-0.91) and Brier score was 0.054 (95% confidence interval, 0.035-0.074). Total spine bone mineral density, total hip bone mineral density, and age had the largest contributions to predicted risk. Using two discrimination thresholds, stratification into low, medium, and high risk, respectively, was associated with likelihood ratios of 0.23, 3.2, and 6.8. At the lower threshold, sensitivity was 0.81, and specificity was 0.82. CONCLUSION: The model developed in this analysis integrates clinical data, serum biomarker levels, and bone mineral densities to predict 10-year risk of osteoporosis with good performance.

Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice.

Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss.

Risk factors of osteoporosis and osteopenia in postmenopausal women based on the L2-L4 BMD T score of the lumbar spine: a study in Iran.

OBJECTIVE: To determine the risk factors of osteoporosis and osteopenia of the spine in postmenopausal women. METHOD: An analytical cross-sectional study was performed on postmenopausal women. The T-score of the lumbar spine (L2-L4) was measured by densitometry and compared between osteoporotic, osteopenia, and normal women. RESULTS: One thousand three hundred fify-nine postmenopausal women were evaluated. The prevalence of osteopenia and osteoporosis was 58.2% and 12.8% respectively. Age, BMI, parity, total breastfeeding years, dairy use, calcium-D supplements, and regular exercise were significantly different in women with osteoporosis, osteopenia, and normal women. Ethnicity, diabetes, and previous fracture history were only other among women with osteoporosis (not osteopenia) and normal women. For osteopenia of the spine, age [AOR 1.08 (1.05-1.11; p < .001)] was the risk factor, and BMI = >30 [AOR 0.36 (0.28-0.58; p < .001)] and BMI 25-<30 [AOR 0.55 (0.34-0.88; p = .012)] were protective factors. Hyperthyroidism (AOR 23.43, p = .010), Kurdish ethnicity (AOR 2.96, p = .009), not having regular exercise (AOR 2.22, p = .012), previous fracture history (AOR 2.15, p = .041)], and age (AOR 1.14, p < .001)], were risk factors for osteoporosis, while BMI ≥30 [AOR 0.09, p < .001], BMI 25-<30 [AOR 0.28, p = .001], and diabetes [AOR 0.41, p = .038] were protective factors for osteoporosis of the spine. CONCLUSION: Hyperthyroidism, low BMI <25, parity ≥ 6, Kurdish ethnicity, not having regular exercise, history of previous fracture, and age, were risk factors for osteoporosis of the spine respectively, while low BMI and age were risk factors for osteopenia.

Association between Phytochemical Index and Osteoporosis in Women: A Prospective Cohort Study in Korea.

Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between phytochemical-rich food intake and osteoporosis incidence in premenopausal and postmenopausal women. The data analyzed included 4600 women aged 40-69 who were free of osteoporosis at baseline, with dietary intake evaluated through a semi-quantitative food frequency questionnaire and osteoporosis prevalence determined using interviewer-administered questionnaires and bone mineral density tests. The phytochemical index (PI) was calculated to reflect the intake levels of phytochemical-rich foods. Postmenopausal women in the highest PI quartile had a 16% lower risk of osteoporosis (95% confidence interval (CI): 0.71 to 0.99, p for trend = 0.02) than those in the lowest quartile, while no significant association was observed among premenopausal women (hazard ratio: 0.98, 95% CI: 0.78 to 1.24, p for trend = 0.8). These findings suggest that consuming phytochemical-rich foods may have a protective effect against osteoporosis in postmenopausal women, offering valuable scientific insights. However, additional research is needed to validate these findings using biochemical data. Overall, this study highlights the potential of dietary interventions to reduce the risk of osteoporosis in postmenopausal women.

Nutrient Patterns and Risk of Osteopenia in Postmenopausal Women.

Nutrient patterns (NPs) and the synergistic effect between nutrients have been shown to be associated with changes in bone mineral density (BMD). This study aimed to identify NPs and to associate them with BMD categories in postmenopausal women. This cross-sectional, observational, analytical study was carried out with women in menopause for at least 12 months, aged ≥50 years. Sociodemographic, lifestyle, and clinical variables were investigated. BMD was assessed using dual energy X-ray absorptiometry. A dietary assessment was conducted using a food frequency questionnaire, and three nutrient patterns (NP1, NP2, and NP3) were extracted from the principal component analysis. Multivariate logistic regression was applied to investigate the association between BMD classifications and NP consumption. A total of 124 women, aged on average, 66.8 ± 6.1 years, were evaluated. Of these, 41.9% had osteopenia and 36.3% had osteoporosis. The NP1 (OR: 6.64, [CI95%: 1.56-28.16]; p = 0.010), characterized by vitamin B12, pantothenic acid, phosphorus, riboflavin, protein (total and animal), vitamin B6, potassium, vitamin D, vitamin E, calcium, cholesterol, ß-carotene, omega 3, magnesium, zinc, niacin, and selenium; and the NP2 (OR: 5.03, [CI95%: 1.25-20.32]; p = 0.023), characterized by iron, vegetable protein, thiamine, folate, fibers (soluble and insoluble), PUFA, vitamin A, vitamin K, alpha-tocopherol, copper, sodium, and retinol, was inversely associated with osteopenia. The lower consumption of NP1 and NP2 by postmenopausal women was associated with a higher risk of osteopenia, but not osteoporosis.

The Effect of Ceratonia siliqua Supplement on Bone Mineral Density in Ovariectomy-induced Osteoporosis in Rats.

AIM: This study aimed to investigate the effect of Ceratonia siliqua on bone mineral density (BMD) as a non-pharmaceutical alternative treatment for postmenopausal osteoporosis. MATERIALS AND METHODS: Thirty mature female Wistar rats were randomly separated into three groups of 10: Control, ovariectomized (OVX), and ovariectomized-plus-C. siliqua (OVX+CS). Total and proximal BMD were measured by dual-energy X-ray absorptiometry (DEXA) in all groups before ovariectomy, and at 3 and 6 months postoperatively. At the end of the study, the femurs were subjected to a three-point bending test. RESULTS: DEXA revealed no statistically significant difference in absolute values or percentage changes for total tibial BMD between OVX+CS and OVX groups throughout the study. In the proximal tibia, both absolute values and BMD percentage changes from baseline were higher in the OVX+CS group compared to the OVX group after 3 and 6 months of C. siliqua administration. Three-point bending test revealed a significantly higher thickness index in the OVX+CS group compared to the OVX group and a higher cross-sectional area index compared to the control group. CONCLUSION: Long-term administration of C. siliqua may be considered a non-pharmaceutical alternative treatment for postmenopausal osteoporosis. Further research is required to properly investigate the effects, and suitable treatment dose and schedule.

Effectiveness of whole-body vibration on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

The present study observed significant effects of whole-body vibration (WBV) on bone mineral density (BMD) in postmenopausal women, with high-quality evidence for high-frequency, low-magnitude, and high-cumulative-dose use. The aim was to update a previous systematic review with meta-analysis to observe the effects of WBV on BMD in postmenopausal women. For the meta-analysis, the weighted mean difference between WBV and control groups, or WBV and conventional exercise, was used for the area of bone mineral density (aBMD) of the lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and Ward's area, or volumetric trabecular bone mineral density (vBMDt) of the radius and tibia. Methodological quality was assessed using the PEDro scale and the quality of evidence using the GRADE system. In total, 23 studies were included in the systematic review and 20 in the meta-analysis. Thirteen studies showed high methodological quality. WBV compared with control groups showed significant effects on aBMD in the primary analysis (lumbar spine and trochanter), sensitivity (lumbar spine), side-alternating vibration (lumbar spine and trochanter), synchronous vibration (lumbar spine), low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high frequency and high magnitude (lumbar spine, trochanter, and Ward's area), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), and positioning with semi-flexed knees (trochanter). Of these results, only high frequency associated with low magnitude and high cumulative dose with low magnitude showed high-quality evidence. At this time, considering the high quality of evidence, it is possible to recommend WBV using high frequency (≈ 30 Hz), low magnitude (≈ 0.3 g), and high cumulative dose (≈ 7000 min) to improve lumbar spine aBMD in postmenopausal women. Other parameters, although promising, need to be better investigated, considering, when applicable, the safety of the participants, especially in vibrations with higher magnitudes (≥ 1 g).

Lophatherum gracile Bronghiart Suppresses Receptor Activator of Nuclear Factor Kappa-B Ligand-Stimulated Osteoclastogenesis and Prevents Ovariectomy-Induced Osteoporosis.

Lophatherum gracile Bronghiart, used in traditional herbal medicine, has many biological properties including antiviral, antipyretic, antitumor, vasorelaxation, and neutrophilic inflammatory effects. However, its modulatory effects on bone metabolism have not been investigated previously. In this study, we examined the effects of a water extract of the leaves of L. gracile (WELG) on osteoclast differentiation and bone loss, and explored its underlying mechanisms. We found that WELG inhibits osteoclastogenesis by suppressing both receptor activator of nuclear factor-κB ligand (RANKL)-induced early activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB)- and RANKL-induced modulation of the positive and negative regulators of osteoclastogenesis in osteoclast precursors. In vivo study demonstrated that WELG protects against bone loss, weight gain, and fat accumulation without affecting uterine atrophy in an ovariectomy-induced postmenopausal osteoporosis mice model. In addition, photochemical analysis of WELG identified active constituents known to have bone-protective effects. Overall, the results of this study suggest that WELG can be a potential candidate for therapy and prevention of postmenopausal osteoporosis.

Normalisation of High Bone Remodelling due to Oestrogen Deficiency by Traditional Chinese Formulation Kang Shuai Lao Pian in Ovariectomised Rats.

Postmenopausal osteoporosis transpires due to excessive osteoclastic bone resorption and insufficient osteoblastic bone formation in the presence of oestrogen insufficiency. Kang Shuai Lao Pian (KSLP) is a red ginseng-based traditional Chinese medicine known for its anti-ageing properties. However, studies on its effect on bone loss are lacking. Thus, the current study examined the skeletal protective effects of KSLP in an ovariectomised rodent bone loss model. Three-month-old female Sprague Dawley rats (n=42) were randomised into baseline, sham and ovariectomised (OVX) groups. The OVX rats were supplemented with low- (KSLP-L; 0.15 g/kg), medium- (KSLP-M; 0.30 g/kg), high-dose KSLP (KSLP-H; 0.45 g/kg) or calcium carbonate (1% w/v). The daily supplementation of KSLP was performed via oral gavage for eight weeks. Gavage stress was stimulated in the ovariectomised control with distilled water. The rats were euthanised at the end of the study. Whole-body and femoral bone mineral content and density scans were performed at baseline and every four weeks. Blood samples were obtained for the determination of bone remodelling markers. Histomorphometry and biomechanical strength testing were performed on femurs and tibias. High bone remodelling typically due to oestrogen deficiency, indicated by the elevated bone formation and resorption markers, osteoclast surface, single-labelled surface and mineralising surface/bone surface ratio, was observed in the untreated OVX rats. Whole-body BMD adjusted to body weight and Young's modulus decreased significantly in the untreated OVX rats. High-dose KSLP supplementation counteracted these degenerative changes. In conclusion, KSLP improves bone health by normalising bone remodelling, thereby preventing bone loss and decreased bone strength caused by oestrogen deficiency. Its anti-osteoporosis effects should be validated in patients with postmenopausal osteoporosis.

Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis.

Osteoporosis is a skeletal system disease characterized by low bone mass and altered bone microarchitecture, with an increased risk of fractures. Classical theories hold that osteoporosis is essentially a bone remodeling disorder caused by estrogen deficiency/aging (primary osteoporosis) or secondary to diseases/drugs (secondary osteoporosis). However, with the in-depth understanding of the intricate nexus between both bone and the immune system in recent decades, the novel field of "Immunoporosis" was proposed by Srivastava et al. (2018, 2022), which delineated and characterized the growing importance of immune cells in osteoporosis. This review aimed to summarize the response of the immune system (immune cells and inflammatory factors) in different types of osteoporosis. In postmenopausal osteoporosis, estrogen deficiency-mediated alteration of immune cells stimulates the activation of osteoclasts in varying degrees. In senile osteoporosis, aging contributes to continuous activation of the immune system at a low level which breaks immune balance, ultimately resulting in bone loss. Further in diabetic osteoporosis, insulin deficiency or resistance-induced hyperglycemia could lead to abnormal regulation of the immune cells, with excessive production of proinflammatory factors, resulting in osteoporosis. Thus, we reviewed the pathophysiology of osteoporosis from a novel insight-immunoporosis, which is expected to provide a specific therapeutic target for different types of osteoporosis.

Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications.

Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota.

Roles of Altered Macrophages and Cytokines: Implications for Pathological Mechanisms of Postmenopausal Osteoporosis, Rheumatoid Arthritis, and Alzheimer's Disease.

Postmenopausal osteoporosis (PMOP) is characterized by the uncoupling of bone resorption and bone formation induced by estrogen deficiency, which is a complex outcome related to estrogen and the immune system. The interaction between bone and immune cells is regarded as the context of PMOP. Macrophages act differently on bone cells, depending on their polarization profile and secreted paracrine factors, which may have implications for the development of PMOP. PMOP, rheumatoid arthritis (RA), and Alzheimer's disease (AD) might have pathophysiological links, and the similarity of their pathological mechanisms is partially visible in altered macrophages and cytokines in the immune system. This review focuses on exploring the pathological mechanisms of PMOP, RA, and AD through the roles of altered macrophages and cytokines secretion. First, the multiple effects on cytokines secretion by bone-bone marrow (BM) macrophages in the pathological mechanism of PMOP are reviewed. Then, based on the thought of "different tissue-same cell type-common pathological molecules-disease pathological links-drug targets" and the methodologies of "molecular network" in bioinformatics, highlight that multiple cytokines overlap in the pathological molecules associated with PMOP vs. RA and PMOP vs. AD, and propose that these overlaps may lead to a pathological synergy in PMOP, RA, and AD. It provides a novel strategy for understanding the pathogenesis of PMOP and potential drug targets for the treatment of PMOP.

Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis.

ABSTRACT: This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.