Increase In Bone Mineral Density Research Articles

Tmem119 is involved in bone anabolic effects of PTH through enhanced osteoblastic bone formation in mice

The intermittent administration of parathyroid hormone (PTH) exerts potent bone anabolic effects, which increase bone mineral density (BMD) and reduce fracture risk in osteoporotic patients. However, the underlying mechanisms remain unclear. Tmem119 has been proposed as a factor that is closely linked to the osteoblast phenotype, and we previously reported that PTH enhanced the expression of Tmem119 in mouse osteoblastic cells. However, roles of Tmem119 in the bone anabolic effects of PTH in vivo remain unknown. We herein investigated the roles of Tmem119 in bone anabolic effects of PTH using Tmem119-deficient mice. Tmem119 deficiency significantly reduced PTH-induced increases in trabecular bone volume and cortical BMD of femurs. Effects of Tmem119 deficiency on bone mass seemed predominant in female mice. Histomorphometric analyses with calcein labeling showed that Tmem119 deficiency significantly attenuated PTH-induced increases in the rates of bone formation and mineralization as well as numbers of osteoblasts. Moreover, Tmem119 deficiency significantly blunted PTH-induced decreases in phosphorylation of β-catenin and increases in alkaline phosphatase activity in osteoblasts. In conclusion, the present results indicate that Tmem119 is involved in bone anabolic effects of PTH through osteoblastic bone formation partly related to canonical Wnt-β-catenin signaling in mice.

Effectiveness of teriparatide in in improving healing rates and bone-turnover markers of osteoporotic hip fracture: a meta-analysis.

To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures. The meta-analysis was done from September to December 2022, and comprised literature search on Wanfang, CNKI, VIP, PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment of the respective database till December 2022. The relevant journals of the library of Macao University of Science and Technology, China, were manually searched for randomised controlled trials of teriparatide in the treatment of osteoporotic hip fractures. The shortlisted studies were subjectd to Cochrane Risk of Bias tool and the Jadad Rating Scale. Meta-analysis was done using the RevMan 5.4 software provided by the Cochrane Collaboration Network. Fracture healing rate and bone mineral density were the primary outcome measures, while mortality, adverse events, malformations, complications, subsequent fractures, timed-up-and-go test, visual analogue scale score, and procollagen type I N-terminal propeptide were the secondary outcome measures. Of the 1,094 articles retrieved, 8(0.7%) randomised controlled trials were analysed. There were 744 patients; 372(50%) in the teriparatide group and 372(50%) in the control group. Fracture healing rate was not significantly different (p=0.82), while bone mineral density was significantly different between the groups (p<0.001). Mortality, adverse events, deformity, and complications were not significantly different (p>0.05), while subsequent fractures, timed-up-and-go score, visual analogue scale score and procollagen type I N-terminal propeptide were significantly different between the groups (p<0.05). The literature did not support teriparatide's ability to improve the healing rate of osteoporotic hip fractures, or to reduce mortality, adverse events, malformations, and complications. In addition, teriparatide could increase bone mineral density of osteoporotic hip fractures and the procollagen type I N-terminal propeptide value, alleviate hip pain, and reduce subsequent fracture rates. This trial is registered with PROSPERO with registration number CRD42022379832.

An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case–control study

SummaryThe impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors.PurposeTo investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA).MethodsIn this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), − 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period.ResultsThe rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD.ConclusionsThe efficacy of ROMO may be attenuated by RA-related factors.

Application value of bone cement containing rhbFGF and RHBMP-2 in PKP treatment of osteoporotic lumbar compression fracture

To investigate the effect of bone cement containing recombinant human basic fibroblast growth factor (rhbFGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in percutaneous kyphoplasty(PKP)treatment of osteoporotic vertebral compression fracture(OVCF). A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed, including 40 males and 63 females, aged from 61 to 78 years old with an average of (65.72±3.29) years old. The injury mechanism included slipping 33 patients, falling 42 patients, and lifting injury 28 patients. The patients were divided into three groups according to the filling of bone cement. Calcium phosphate consisted of 34 patients, aged(65.1±3.3) years old, 14 males and 20 females, who were filled with calcium phosphate bone cement. rhBMP-2 consisted of 34 patients, aged (64.8±3.2) years old, 12 males and 22 females, who were filled with bone cement containing rhBMP-2. And rhbFGF+rhBMP-2 consisted of 35 patients, aged (65.1±3.6) years old, 14 males and 21 females, who were filled with bone cement containing rhbFGF and rhBMP-2. Oswestry disability index (ODI), bone mineral density, anterior edge loss height, anterior edge compression rate of injured vertebra, visual analog scale (VAS) of pain, and the incidence of refracture were compared between groups. All patients were followed for 12 months. Postoperative ODI and VAS score of the three groups decreased (P<0.001), while bone mineral density increased (P<0.001), anterior edge loss height, anterior edge compression rate of injured vertebra decreased first and then slowly increased (P<0.001). ODI and VAS of group calcium phosphate after 1 months, 6 months, 12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05), bone mineral density after 6 months, 12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05), and anterior edge loss height, anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05). There was no statistical difference in the incidence of re-fracture among the three groups (P>0.05). Bone cement containing rhbFGF and rhBMP-2 could more effectively increase bone mineral density in patients with OVCF, obtain satisfactory clinical and radiological effects after operation, and significantly improve clinical symptoms.

Microbiome dysbiosis by antibiotics protects cartilage degradation in OAOP mice.

The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.

Adaptive enhancement of apatite crystal orientation and Young's modulus under elevated load in rat ulnar cortical bone

Functional adaptation refers to the active modification of bone structure according to the mechanical loads applied daily to maintain its mechanical integrity and adapt to the environment. Functional adaptation relates to bone mass, bone mineral density (BMD), and bone morphology (e.g., trabecular bone architecture). In this study, we discovered for the first time that another form of bone functional adaptation of a cortical bone involves a change in bone quality determined by the preferential orientation of apatite nano-crystallite, a key component of the bone. An in vivo rat ulnar axial loading model was adopted, to which a 3–15 N compressive load was applied, resulting in approximately 440–3200 μɛ of compression in the bone surface. In the loaded ulnae, the degree of preferential apatite c-axis orientation along the ulnar long axis increased in a dose-dependent manner up to 13 N, whereas the increase in BMD was not dose-dependent. The Young's modulus along the same direction was enhanced as a function of the degree of apatite orientation. This finding indicates that bone has a mechanism that modifies the directionality (anisotropy) of its microstructure, strengthening itself specifically in the loaded direction. BMD, a scalar quantity, does not allow for load-direction-specific strengthening. Functional adaptation through changes in apatite orientation is an excellent strategy for bones to efficiently change their strength in response to external loading, which is mostly anisotropic.

Osteoporosis and Leptin: A Systematic Review.

Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities. The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI. Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased. Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.

Effects of Exogenous GIP and GLP-2 on Bone Turnover in Individuals With Type 2 Diabetes.

Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density. The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption. The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D. We included 10 men with T2D. Participants met fasting in the morning on 3 separate test days and were injected subcutaneously with GIP, GLP-2, or placebo in a randomized crossover design. Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH. GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (P = .001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP. Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals.

The Effects of Switch Therapy in Osteoporosis Treatment after Romosozumab after Comparing with Prior Treatment.

Rationale. Although romosozumab is one of the most effective treatments for osteoporosis by increasing bone mineral density in the lumbar spine and femur and recommended for denosumab as switch therapy, these effects regarding its prior treatment have not yet been evaluated clearly. This study focused on the effects of switch therapy from romosozumab to denosumab in regard to prior treatment of osteoporosis including bone mineral density and bone turnover marker and other related factors. Patient Concerns. 15 osteoporotic patients were assigned to the naïve group, 15 were assigned to the teriparatide group, and 10 were assigned to the bisphosphonate group. Interventions. Patients who were treated as outpatients for osteoporosis with romosozumab for 1 year and switched to denosumab between 2020 and 2022 at our hospital were examined. Our hospital registry included 40 osteoporotic patients who were over 65 years of age with bone mineral density (bone mineral density): T score <-2.5 standard deviations (SDs) and fracture assessment tool (FRAX) score >20%. Outcomes. The naïve group had the highest increase in LS BMD among these three groups during switch therapy from romosozumab to denosumab, while there were no significant differences about adverse drug events and serum Ca concentration among them. There was no incidence of fracture. Conclusion. These findings indicate that the effects of osteoporotic treatment of switch therapy from romosozumab to denosumab were likely to affect prior treatment of osteoporosis.

Mucosal TLR5 activation controls healthspan and longevity

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Bone-targeting engineered milk-derived extracellular vesicles for MRI-assisted therapy of osteoporosis.

The imbalance between osteoblasts and osteoclasts is the cause of osteoporosis. Milk-derived extracellular vesicles (mEVs), excellent drug delivery nanocarriers, can promote bone formation and inhibit bone resorption. In this study, we conjugated bone-targeting peptide (AspSerSer, DSS)6 to mEVs by click chemistry and then loaded with SRT2104, a SIRT1 (silent mating-type information regulation 2 homolog 1) agonist that was proofed to help reduce bone loss. The engineered (DSS)6-mEV-SRT2104 had the intrinsic anti-osteoporosis function of mEVs and SRT2104 to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis. Furthermore, we labelled mEVs with MnB nanoparticles that can be used for the in vivo magnetic resonance imaging (MRI) visualization. The obtained nanocomposites significantly prevented bone loss in osteoporosis mice and increased bone mineral density, exhibiting superior bone accumulation under MRI. We believe the proposed (DSS)6-mEV-SRT2104/MnB provides a novel paradigm for osteoporosis treatment and monitoring.

Comparison of bone mineral density of runners with inactive males: A cross-sectional 4HAIE study.

The purpose of the study was to determine whether running is associated with greater bone mineral density (BMD) by comparing the BMD of regularly active male runners (AR) with inactive nonrunner male controls (INC). This cross-sectional study recruited 327 male AR and 212 male INC (aged 18-65) via a stratified recruitment strategy. BMD of the whole body (WB) and partial segments (spine, lumbar spine (LS), leg, hip, femoral neck (FN), and arm for each side) were measured by dual-energy x-ray absorptiometry (DXA) and lower leg dominance (dominant-D/nondominant-ND) was established by functional testing. An ANCOVA was used to compare AR and INC. The AR had greater BMD for all segments of the lower limb (p<0.05), but similar BMD for all segments of the upper limb (p>0.05) compared with INC. Based on the pairwise comparison of age groups, AR had greater BMD of the ND leg in every age group compared with INC (p<0.05). AR had grater BMD of the D leg in every age group except for (26-35 and 56-65) compare with INC (p<0.05). In the youngest age group (18-25), AR had greater BMD in every measured part of lower extremities (legs, hips, femoral necks) compared with INC (p<0.05). In the 46-55 age group AR had greater BMD than INC (p < 0.05) only in the WB, D Leg, D neck, and ND leg. In the 56-65 age group AR had greater BMD than INC (p<0.05) only in the ND leg. Overall, AR had greater BMD compared with INC in all examined sites except for the upper limbs, supporting the notion that running may positively affect bone parameters. However, the benefits differ in the skeletal sites specifically, as the legs had the highest BMD difference between AR and INC. Moreover, the increase in BMD from running decreased with age.

Effect of Achieving Sustained SDAI Remission on Erosion Healing in Early Rheumatoid Arthritis - A One-year Prospective HR-pQCT Study

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive joint destruction. High-resolution peripheral quantitative CT (HR-pQCT) is a novel technique for detailed bone microstructure analysis allowing volumetric assessment of bone erosions. While most patients demonstrating little baseline joint damage on radiography in the early stage of RA, whether achieving simple disease activity index (SDAI) remission can lead to better structural outcome is to be confirmed. Methods Patients with ERA were recruited and treated to the target of simple disease activity index (SDAI) remission using a standardized algorithm. One hundred patients who received the one-year tight-control treatment were grouped by achieving SDAI sustained LDA [SDAI [Formula: see text] at 6, 9 and 12 months (sLDA group) or not (non-sLDA group). HR-pQCT of the second to fourth metacarpophalangeal joints were performed at baseline, month 6 and one-year. Erosion volume and marginal bone mineral density (BMD) were measured. On an individual patient basis, erosion progression was defined as at least one erosion showing (1) an increase in erosion volume exceeding the smallest detectable change [SDC] (0.08 mm 3) AND (2) a decrease in marginal BMD exceeding SDC (7.8 mmHA/cm 3). Erosion healing was defined as at least one erosion showing (1) a reduction in erosion volume greater than SDC AND an increase in BMD exceeding SDC OR complete disappearance of the lesion AND (2) the absence of any erosion progression. Results Fourteen patients (12.8%) achieved sustained SDAI remission from 6-12 months (SDI group). After 12 months, a significant reduction in erosion volume and marginal osteosclerosis was observed in both groups. The SDI group showed a lower incidence of erosion progression (increase in volume [Formula: see text]0.08mm 3 and decrease in marginal osteosclerosis [Formula: see text]7.8mg HA/cm 3 : 0% vs 16%, p=0.135) and exhibited a higher rate of erosion healing (56% vs 29%, p=0.083) compared with the non-SDI group. In the GEE model, patients in the SDI group showed a higher likelihood of erosion healing (OR: 2.976, 95% CI: 1.0 - 8.9, p=0.050). The changes in erosion depth and width were similar between two groups. Conclusion Achieving sustained SDAI remission could improve erosion healing and limit erosion progression in patients with ERA.

Warming acupuncture-moxibustion combined with Bushen Qianggu Recipe effectively improves bone metabolism in osteoporosis patients.

Osteoporosis (OP) increases the risk of fractures in older adults, with no effective treatment options at present. To analyze the effects of warming acupuncture-moxibustion (WAM) combined with Bushen Qianggu Recipe on bone metabolism, bone mineral density (BMD), and pain intensity in OP patients. This retrospective study involved 103 patients with OP who were admitted to Wuhan Hospital of Traditional Chinese Medicine between July 2021 and December 2023. The control group consisted of 47 cases given WAM and the research group consisted of 56 cases receiving WAM + Bushen Qianggu Recipe (Rehmanniae Radix 15 g, Radix Rehmanniae Preparata 15 g, Poria cocos 10 g, yam 10 g, rhizoma alismatis 10 g, raspberry 10 g, medlar 10 g, Schisandra chinensis 10 g, Semen Cuscutae 10 g, Epimedium 10 g, Polygonatum sibiricum Red. 10 g, Drynaria 10 g, and Eucommia ulmoides 10 g). Bone metabolism markers (procollagen type I N-terminal propeptide (PINP) and bone-specific alkaline phosphatase (B-ALP)), BMD (lumbar vertebrae at L2-4, femoral neck, and distal 1/3 of the radius), pain intensity (visual analog score (VAS)), dysfunction (Oswestry Dysfunction Index), quality of life (Short-Form 36 Item Health Survey (SF-36)), and overall treatment efficacy were analyzed comparatively. Compared with the baseline (before treatment) and post-treatment levels in the control group, the research group showed a reduction in PINP and B-ALP, an increase in BMD at the lumbar vertebrae L2-4, femoral neck, and distal 1/3 of the radius, and a decrease in VAS and Oswestry Disability Index scores. Additionally, the research group performed better across various dimensions of the SF-36 scale and had a higher overall effective rate. WAM combined with Bushen Qianggu Recipe is effective in alleviating pain intensity and improving bone metabolism, BMD, and quality of life in OP patients; therefore it is deserving of clinical promotion.

Effect of Plyometrics on Bone Mineral Density in Young Adults: A Systematic Review and Meta-Analysis

ABSTRACT Context Osteoporosis is a chronic bone metabolic disease characterized by decreased bone mass, leading to increased frailty and a subsequent fracture risk. Peak bone mineral density (BMD) is achieved in early adulthood and may be the most important factor leading to the development of osteoporosis in older adults. Objective This study aimed to analyze the effects of plyometrics on BMD in young men and premenopausal women. Design This study used randomized controlled trials found in MEDLINE, Embase, and CINAHL published between January 1, 1990, and November 1, 2022. Keywords included plyometrics, jumping, jump training, bone health, and bone mineral density. Articles were assessed for methodological quality using the Consolidated Standards of Reporting Trials 2010 checklist. Eligibility Criteria Randomized controlled trials investigating BMD in healthy premenopausal women and men between the ages of 18 and 60 yr that compared plyometrics with control were included. Study Selection Two reviewers independently screened 553 abstracts. Main Outcome Measures Mean baseline and follow-up dual-energy x-ray absorptiometry scores and standard deviations were extracted to calculate the standard mean difference. After extraction, the magnitude of difference between control and treatment groups were analyzed using the Hedges and Olkin method for effect size. Results The 12 included studies had high methodological quality. Of the 12 studies, 10 reported statistically significant increase in BMD at ≥1 site when compared with control. Two studies showed equal improvement when compared with resistance-only training. After analysis, a large positive effect size with strongly positive correlation was seen between plyometrics and lumbar spine BMD. Conclusion Plyometric training is a safe and time-efficient method to improve BMD in premenopausal people 18–65 yr old. Large effect sizes were associated with increased training intensity and lasted months after the intervention was complete. Plyometrics seems to be a comparable alternative to resistance training with respect to bone health.

Association between serum insulin-like growth factor-1 and bone mineral density in patients with type 2 diabetes.

Secondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM. A retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation. A significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (β 0.02, 95% CI 0.01, 0.04 for LS; β 0.02, 95% CI 0.01, 0.03 for FN; β 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (β -0.04, 95% CI -0.10, 0.01 for LS; β -0.04, 95% CI -0.08, 0.01 for FN; β -0.03, 95% CI -0.08, 0.01 for TH). These findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold.

Synergistic anti-osteoporosis effects of Anemarrhena asphodeloides bunge-Phellodendron chinense C.K. Schneid herb pair via ferroptosis suppression in ovariectomized mice.

Ferroptosis plays a crucial role in the progression of postmenopausal osteoporosis. Anemarrhena asphodeloides Bunge/Phellodendron chinense C.K. Schneid (AA/PC) is the core herb pair in traditional Chinese medicines formulae for postmenopausal osteoporosis treatment. However, the synergistic effects, and mechanisms, of AA/PC on alleviating ferroptosis and postmenopausal osteoporosis remain unclear. The goal herein was to analyze the effective ingredients and molecular mechanisms of AA/PC in the treatment of osteoporosis through serum pharmacochemistry, network pharmacology, metabolomics analysis, and pharmacodynamics evaluation. A bilateral ovariectomized (OVX) mouse model was established. Micron-scale computed tomography analysis showed that AA/PC increased bone mineral density in OVX mice. The effects of AA/PC were better than AA or PC alone on inhibiting the bone resorption marker nuclear factor of activated T-cells 1. Furthermore, five absorbable compounds were detected in serum: mangiferin, magnoflorine, berberine, timosaponin BIII, and timosaponin AIII. Network pharmacology showed these compounds had close relationship with seven ferroptosis targets. Importantly, compared with AA or PC alone, the AA/PC herb pair exerted better effects on regulating crucial ferroptosis pathways, including the system xc-/glutathione/glutathione peroxidase 4, transferrin receptor/ferritin, and acyl-CoA synthetase long chain family member 4/polyunsaturated fatty acids signaling pathways. These results indicate that AA/PC exerts synergistic effects on regulating glutathione synthesis, iron homeostasis, and lipid metabolism in ferroptosis. This work lays the foundation for further development and use of AA/PC herb pair for preventing and treating postmenopausal osteoporosis.

Clinical effectiveness of calcitriol and calcium gluconate in treating older male patients with osteoporosis

Clinical studies on calcitriol in osteoporosis (OP) have been mostly conducted in postmenopausal women, with limited research reported in elderly male patients. In this study, we investigated the effects of combining calcitriol with calcium gluconate for treating OP in elderly men and compared it with calcium gluconate monotherapy to provide insights into the clinical treatment options for OP. A total of 86 elderly male OP patients were included in this study and randomly assigned to control or observation groups in a 1:1 ratio. The control group was given oral calcium gluconate (1.0 g, three times daily), while the observation group was given oral calcitriol capsule (0.25 µg twice daily) and oral calcium gluconate (1.0 g three times daily). The results indicated that treatment with single calcium gluconate for 6 months had minimal impact on the bone mineral density (BMD) of the lumbar spine, total hip and femoral neck, and balance function. In contrast, the combination of calcium gluconate and calcitriol significantly increased BMD and improved patients’ balance function. Both single calcium gluconate treatment and the combination of calcium gluconate and calcitriol affected various bone metabolism and turnover markers to varying degrees, including a decrease in the level of tartrate-resistant acid phosphatase-5b (TRAP-5b) and an increase in the levels of osteocalcin and calcium. Both calcium gluconate and calcitriol affect patients’ bone metabolism and turnover markers to varying degrees. Importantly, the combination of calcium gluconate and calcitriol had a significant effect on these markers compared to calcium gluconate monotherapy, and no significant difference in the incidence of adverse reactions was observed between the two groups during treatment. Calcium gluconate in combination with calcitriol in elderly male patients with OP may increase bone mineral density, improve bone metabolism, enhance bone turnover and maintain a high safety profile.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

Effects of tibolone combined with zoledronic acid on bone density, bone metabolism, and pain in postmenopausal patients with osteoporosis.

To explore the efficacy and safety of tibolone combined with zoledronic acid in the treatment of postmenopausal osteoporosis (PMO). We conducted a retrospective analysis of 121 PMO patients from March 2019 to July 2021. Patients were divided into two groups based on treatment regimen: an observation group (n=62) receiving zoledronic acid combined with tibolone and a control group (n=59) receiving tibolone monotherapy. We evaluated and compared therapeutic efficacy, bone mineral density, bone metabolism markers (osteocalcin, serum C-terminal telopeptide of type I collagen, and bone alkaline phosphatase), pain, knee joint function, incidence of fragility fractures, and adverse reactions. Logistic regression analysis was used to evaluate risk factors affecting treatment efficacy. The observation group showed a significantly higher therapeutic effect (96.77%) compared to the control group (83.05%), and a lower incidence of fragility fractures (P=0.012). Before treatment, there were no significant differences in bone mineral density, bone metabolism markers, pain status, or knee function between the two groups (all P>0.05). However, after treatment, evaluations showed marked improvements in these parameters in both groups, with more significant enhancements observed in the observation group (all P<0.001). The incidence of adverse reactions did not significantly differ between the groups (20.97% vs 13.56%, P=0.282). Logistic regression analysis identified the use of tibolone combined with zoledronic acid as a protective factor for effective treatment. Tibolone combined with zoledronic acid significantly increases bone mineral density, improves bone metabolism, and reduces pain in PMO patients, with a safety profile comparable to that of monotherapy. This regimen should be considered for clinical use in treating PMO.