Levels Of Bone Resorption Markers Research Articles

Comparison of efficacy of romosozumab with denosumab and risedronate in patients newly initiating glucocorticoid therapy

Abstract Context Wnt/β-catenin signaling pathway is one of the pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP). We previously reported the potential of inhibiting sclerostin as a treatment for GIOP. Objective To compare the efficacy of romosozumab (ROMO), a monoclonal antibody against sclerostin, with existing therapy for GIOP. Methods Patients with rheumatic diseases who had not previously received treatment for osteoporosis and were newly treated with prednisolone 15 mg/day or more were randomly assigned to receive ROMO, denosumab (DMAb), or bisphosphonates (BP). After the initiation of GC therapy, we measured the bone mineral density (BMD) of the lumbar spine, femoral neck, and total hip every 6 months and bone turnover markers every 3 months for 12 months. Results Eleven patients were assigned to the ROMO group, 14 to the DMAb group, and 14 to the BP group. The median [25th to 75th percentile] percent change in lumbar spine BMD from baseline at 12 months was the greatest in the ROMO group (ROMO; 8.6 [3.1–12.4] %, DMAb; 3.3 [1.5–6.2] %, BP; -0.4 [-3.4–1.1] %). Among bone formation markers, serum levels of bone alkaline phosphatase were slightly elevated in the ROMO group, while those of N-terminal propeptide of type I procollagen and osteocalcin decreased in all three groups; however, these changes were smaller in the ROMO group. Serum levels of bone resorption markers and a urine bone quality marker decreased in all groups. Conclusion Treatment with ROMO significantly increased lumbar spine BMD in GC-treated patients, suggesting that ROMO is effective for GIOP.

9172 Contrasting Bone Profiles In Pcos Are Related To Bmi: A Systematic Review And Meta-analysis

Abstract Disclosure: M.O. Premaor: None. G. Risseti: None. J. Piovezan: None. F.V. Comim: None. Polycystic ovary syndrome (PCOS) is a complex and multifaceted disorder that may affect bone health. Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty. We conducted a systematic review and meta-analysis of published research on bone mineral density (BMD), bone markers, and the risk of fractures in individuals with PCOS. We searched MEDLINE, Embase, and conference s and preprints. Studies were eligible if the PCOS was defined according to the NIH criteria, the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group criteria, AE-PCOS society criteria, or ICD codes. The endpoints studied included fractures, bone mineral density (BMD), and bone markers. The study protocol is available at PROSPERO (CRD42016049664). From the 3322 studies identified in the databases, 111 had their full texts evaluated, and 31 studies met the inclusion criteria for qualitative analysis. Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. No differences were observed between individuals with PCOS and the control group in the pooled analysis for the whole group. Nevertheless, contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Women with PCOS and a mean BMI <27 kg/m2 exhibited lower spine BMD (MD -0.060; 95% CI, -0.110 and -0.011) and total hip BMD (MD -0.042; 95% CI, -0.068 and -0.017), and increased bone resorption marker (CTX) levels (SMD 0.38; 95%CI 0.03 and 0.72). Conversely, women with PCOS and a mean >27 kg/m2 exhibited increased spine BMD (MD 0.029; CI 95%, 0.009 to 0.048) and total hip BMD (MD 0.036; CI 95%, 0.010 to 0.063), with no significant changes in bone resorption markers. Due to the limited number of longitudinal studies available, it was not possible to determine the risk of bone fractures in both groups. In conclusion, the findings of this systematic review show a negative impact of PCOS on bone health in women with a BMI <27 kg/m2, suggesting that increased surveillance and research for bone disease may be necessary for this particular group. Presentation: 6/3/2024

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

GCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice.

C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)‑induced mice via the AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2‑related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3‑E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro‑computed tomography scans and bone‑related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate‑resistant acid phosphatase (TRAP) staining. Runt‑related transcription factor‑2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C‑telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N‑terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3‑E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription‑quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX‑induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3‑E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3‑E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.

Contrasting Bone Profiles in PCOS Are Related to BMI: A Systematic Review and Meta-analysis.

Controversial results have emerged regarding whether polycystic ovary syndrome (PCOS) is protective or increases the risk of bone frailty. This study investigated whether the PCOS condition affects bone parameters of premenopausal women. This is an update for a previous meta-analysis published in 2019. We searched MEDLINE and Embase. Studies were considered eligible for the update if published in English between October 1, 2018, and December 31, 2023. The diagnosis of PCOS should be based on National Institutes of Health criteria, the Rotterdam Consensus, Androgen Excess & PCOS Society criteria, or International Classification of Diseases codes in women over 18 years old. Only records with the Newcastle-Ottawa Scale ≥ 6 were selected for data extraction. Data were extracted by 2 independent reviewers. We identified 31 studies that met the inclusion criteria for qualitative analysis from 3322 studies in the whole period (1990-2023). Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30 305 women with PCOS and 10,1907 controls. Contrasting profiles emerged after stratification using a body mass index (BMI) cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and nonvertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (C-terminal type I collagen) levels. Conversely, individuals with PCOS and a BMI ≥27 kg/m2 exhibited increased vertebral and nonvertebral bone mineral density, with no significant changes in bone formation and resorption markers (except osteocalcin). The findings of this study alert for a low bone mass, low bone formation, and increased bone resorption PCOS with a BMI <27 kg/m2.

Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway

ABSTRACT Objective Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. Methods We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Results Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine’s promotive effect. Conclusion Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

Erosion Regression in Patients with RA After Upadacitinib-A Pilot Study Using High Resolution Peripheral Quantitative Computed Tomography

Background: Janus kinases inhibitor (JAKi) is a potent drug in treating patients with rheumatoid arthritis (RA). However, the effect of JAKi on finite structural changes remained uncertain. This study aims to investigate the effect of JAKi on erosion repair evaluated by high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active RA. Methods: This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with [Formula: see text]1 bone erosion on HR-pQCT. They were given upadacitinib 15mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Results: Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23± 3.26mm3vs control group: 1.32± 6.05mm3, p=0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p=0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p=0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Conclusion: Despite a similar improvement in RA disease activity after upadacitinib compared to csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Минеральная плотность костной ткани у молодых пациентов с воспалительными заболеваниями кишечника

Inflammatory bowel diseases (IBD) are characterized by the development of various systemic manifestations. One of the significant extraintestinal manifestations of IBD is a decrease in mineral density (BMD) (demineralization) of bone tissue and osteoporosis (OP). The pathogenesis of decreased BMD is multifactorial: the activity of immune inflammation of the gastrointestinal mucosa, medication intake, malnutrition (low calcium intake), decreased muscle and fat mass, vitamin D deficiency, as well as other factors contribute to the development of osteoporosis in such patients. Despite various studies examining the prevalence of decreased BMD in patients with IBD, data vary widely, ranging from 17 to 77%. The purpose is to evaluate BMD, levels of bone resorption markers in young patients with IBD, and to evaluate the relationship between BMD and osteosynthesis markers. Materials and methods. 62 patients with a verified diagnosis of IBD were examined: 30 patients had Crohn’s disease (CD), 32 patients had ulcerative colitis (UC). All patients underwent a general clinical examination, a double-absorption X-ray densitometric study with determination of BMD and bone mineral content (BMC), as well as determination of bone resorption parameters — osteocalcin, Beta-Crosslaps (C-terminal telopeptides of type I collagen) and marker determination formation of bone matrix P1NP. The level of the mineral part of bone mass was measured using the bioimpedance method on the ABC-02 «MEDASS» apparatus. Results: Seven patients with IBD (11%) had low BMD for chronological age. The median values of BMD, osteocalcin, Beta-Crosslaps, and bone matrix formation marker P1NP in the general group of patients with IBD, as well as in the subgroups of patients with CD and UC are presented. A clinical example is presented. Conclusion. Diagnosis of osteoporosis in patients with IBD is difficult for several reasons. It is important to assess the presence of risk factors in conjunction with laboratory and instrumental examinations.

Increased Bone Turnover and Decreased BCMA Levels in Patients with Response to Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma

Introduction For most patients (pts), multiple myeloma (MM) remains an incurable disease. Osteolytic lesions (OL) are present in 80% of pts at diagnosis and skeletal-related events are the most common cause for symptomatic relapse. Hence, myeloma bone disease (MBD) is a major cause of morbidity and mortality especially among pts with relapsed/refractory MM (RRMM). B cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T cells have revolutionized treatment of patients with RRMM. While remission rates are high and pts experience long-standing treatment free intervals after CAR T cell treatment, little is known about its effects on MBD and bone turnover. The latter can be determined in plasma by measuring markers of bone formation and resorption. We aimed to analyze the longitudinal development of bone turnover during and after anti-BCMA CAR T cell treatment in RRMM pts. Methods We analyzed 28 consecutive pts with RRMM who underwent treatment with either Idecabtagene-Vicleucel (n=27) or Ciltacabtagen-Autoleucel (n=1) at our center between December 2021 and February 2023. Median age at infusion was 63 (range 39-75) years. 57% of pts were male. All pts were triple-class exposed, 21% had penta-class refractory disease. Status prior to CAR T cell infusion was complete remission (CR, 11%), partial remission (PR, 21%), very good PR (14%), stable disease (4%), or progressive disease (PD, 50%). The impact of CAR T cell treatment on bone turnover was assessed by collecting plasma samples on the day of T cell apheresis, as well as days (d) 30 and 100 after CAR T cell infusion. Samples were analyzed by ELISA to evaluate plasma levels of bone formation marker Osteocalcin (OCN), bone resorption markers Tartrate-resistant acid phosphatase 5b (TRAcP5b) and fibroblast growth factor 23 (FGF23) as well as BCMA as a marker for the targeted myeloma cells. Median levels were compared between subgroups by Wilcoxon tests. Remission status after CAR T cell therapy was first evaluated at d 30 according to International Myeloma Working Group consensus criteria. Median follow-up was 6 months. Results Of the 28 pts treated with anti-BCMA CAR T cells, 64% achieved at least a PR (responders), while 36% had PD shortly (30 d) after. Within 14 d after infusion, 82% developed a cytokine release syndrome (CRS, °I or II), in 30% of which Tocilizumab was applied. Only 1 pt developed immune effector cell-associated neurotoxicity syndrome. In responders, BCMA levels in plasma decreased significantly between apheresis and d 30 ( P&amp;lt;.01) and between apheresis and d 100 ( P&amp;lt;.01), while pts with PD showed no significant change in BCMA levels at the same timepoints ( P=.6 and P=.8). Furthermore, BCMA levels were significantly higher in pts with PD at d 30 ( P&amp;lt;.01) and d 100 ( P=.02), compared to responders (Figure 1). Regarding bone resorption markers, TRAcP5b levels were significantly increased in responders ( P=.01) but not pts with PD ( P=.56) on d 30 after apheresis. Furthermore, we determined a significant increase of intact FGF23 between apheresis and d 30 ( P&amp;lt;.01) and a subsequent significant decrease of intact FGF23 ( P=.02) between d 30 and d 100 in responders. Since FGF23 and interleukin-6 (IL-6) are physiologically dependent, the observed FGF23 dynamics are likely to be an effect of increasing IL-6 in the context of CRS. Aptly, pts who received Tocilizumab because of full-blown CRS had higher intact FGF23 levels at d 30 ( P=.02) compared to pts without Tocilizumab treatment. The bone formation marker OCN showed a significant increase in responders between apheresis and d 100 ( P=.01), as well as between d30 and d100 ( P=.02), while there were no significant changes in OCN levels over the time in pts with PD (Figure 2). Conclusion Pts responding to treatment with anti-BCMA CAR T cells, showed an increased bone turnover shortly after infusion. The increase of bone resorption marker levels appeared to be a short-term trend and could possibly be related to inflammation and high interleukin levels during the first days after infusion. However, we also saw a steady increase of bone formation marker OCN, which remained significant till d 100 in responders. Our data implies, that response to anti-BCMA CAR T cells is accompanied by increasing bone formation. Further analyses are needed to evaluate, whether this treatment can have positive long-term effects on MBD.

MiR-196b-5p Regulates Osteoblast and Osteoclast Differentiation and Bone Homeostasis by Targeting SEMA3A.

miR-196b-5p plays a role in various malignancies. We have recently reported its function in regulating adipogenesis. However, it remains to be clarified whether and how miR-196b-5p affects bone cells and bone homeostasis. In this study, in vitro functional experiments showed an inhibitory effect of miR-196b-5p on osteoblast differentiation. Mechanistic explorations revealed that miR-196b-5p directly targeted semaphorin 3a (Sema3a) and inhibited Wnt/β-catenin signaling. SEMA3A attenuated the impaired osteogenesis induced by miR-196b-5p. Osteoblast-specific miR-196b transgenic mice showed significant reduction of bone mass. Trabecular osteoblasts were reduced and bone formation was suppressed, whereas osteoclasts, marrow adipocytes, and serum levels of bone resorption markers were increased in the transgenic mice. The osteoblastic progenitor cells from the transgenic mice had decreased SEMA3A levels and exhibited retarded osteogenic differentiation, whereas those marrow osteoclastic progenitors exhibited enhanced osteoclastogenic differentiation. miR-196b-5p and SEMA3A oppositely regulated the expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin. The calvarial osteoblastic cells expressing the transgene promoted osteoclastogenesis, whereas the osteoblasts overexpressing Sema3a inhibited it. Finally, in vivo transfection of miR-196b-5p inhibitor to the marrow reduced ovariectomy-induced bone loss in mice. Our study has identified that miR-196b-5p plays a key role in osteoblast and osteoclast differentiation and regulates bone homeostasis. Inhibition of miR-196b-5p may be beneficial for amelioration of osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Increased BMP-Smad signaling does not affect net bone mass in long bones.

Bone morphogenetic proteins (BMPs) have been used for orthopedic and dental application due to their osteoinductive properties; however, substantial numbers of adverse reactions such as heterotopic bone formation, increased bone resorption and greater cancer risk have been reported. Since bone morphogenetic proteins signaling exerts pleiotropic effects on various tissues, it is crucial to understand tissue-specific and context-dependent functions of bone morphogenetic proteins. We previously reported that loss-of-function of bone morphogenetic proteins receptor type IA (BMPR1A) in osteoblasts leads to more bone mass in mice partly due to inhibition of bone resorption, indicating that bone morphogenetic protein signaling in osteoblasts promotes osteoclast function. On the other hand, hemizygous constitutively active (ca) mutations for BMPR1A (caBmpr1a wt/+ ) in osteoblasts result in higher bone morphogenetic protein signaling activity and no overt skeletal changes in adult mice. Here, we further bred mice for heterozygous null for Bmpr1a (Bmpr1a +/- ) and homozygous mutations of caBmpr1a (caBmpr1a +/+ ) crossed with Osterix-Cre transgenic mice to understand how differences in the levels of bone morphogenetic protein signaling activity specifically in osteoblasts contribute to bone phenotype. We found that Bmpr1a +/- , caBmpr1a wt/+ and caBmpr1a +/+ mice at 3months of age showed no overt bone phenotypes in tibiae compared to controls by micro-CT and histological analysis although BMP-Smad signaling is increased in both caBmpr1a wt/+ and caBmpr1a +/+ tibiae and decreased in the Bmpr1a +/- mice compared to controls. Gene expression analysis demonstrated that slightly higher levels of bone formation markers and resorption markers along with levels of bone morphogenetic protein-Smad signaling, however, there was no significant changes in TRAP positive cells in tibiae. These findings suggest that changes in bone morphogenetic protein signaling activity within differentiating osteoblasts does not affect net bone mass in the adult stage, providing insights into the concerns in the clinical setting such as high-dose and unexpected side effects of bone morphogenetic protein application.

Osoblyvosti stanu mineralnoi shchilnosty kistkovoi tkanyny u cholovikiv, khvorykh na ankilozyvnyi spondylit: chastota y kharakter porushen; vmist metabolichnykh pokaznykiv syntezu ta rezorbtsii kistkovoi tkanyny, vitaminu D v syrovattsi krovy; dostovirni chynnyky porushen

Introduction. Decreased bone mineral density (BMD) and the development of osteoporosis are common and poorly understood complications of ankylosing spondylitis (AS). Increased bone turnover and high inflammatory activity are important in the pathophysiology of AS-associated osteoporosis, and markers of bone remodeling are valuable markers for detecting bone loss The aim of the study. To find out the features of the BMD state in men with AS, based on establishing the frequency and nature of BMD violations, determining the content of metabolic indicators of bone tissue synthesis and resorption, vitamin D in blood serum, as well as identifying reliable factors involved in its violations. Materials and methods. The research group consisted of 83 men with AS, with an average age of 40.7 ± 0.8 years and a disease duration of 8.7 ± 0.5 years. Disease activity was determined by the BASDAI, ASDAS-CRB index. Laboratory examination included determination of C-reactive protein (CRP) and markers of bone tissue metabolism and vitamin D. BMD was measured using dual-energy X-ray absorptiometry Results. In men with AS, osteoporosis is found in 33.7 % of people, osteopenic syndrome in 28.9 % of patients, and normal indicators of BMD in 37.4 % of patients. We showed that low bone mass was closely related to the total indicators of the activity of the inflammatory process according to ASDAS, BASDAI and CRP content. In particular, in the group of patients with a very high degree of activity, the share of people with osteoporosis was equal to 78.6 %, and was 1.8 times higher than in the group of patients with moderate activity of AS. Similar patterns were observed for the BASDAI activity index and the pro-inflammatory marker CRP. In men with AS, the processes of bone resorption prevail over the processes of biosynthesis of bone tissue, as indicated by the preserved concentration of synthesis markers (OC, PINP) and the increase of the bone resorption marker (NTx) in blood serum. In addition, in the group of patients with osteoporosis, a high content of NTx was found in every second patient, and the average concentration was 39.0 % higher than in the group with preserved BMD. Loss of bone mass is closely related to a deficiency of vitamin D. Thus, in the group of patients with osteoporosis, in addition to probably low levels of vitamin D, a high proportion of people (57.2 %) with a severe deficiency was found, the insufficient level was in 43% and the optimal level equal to only 29.0 % of people. Conclusions. Patients with AS have a high frequency (62.6 %) of a decrease in BMD, while OP occurs in every third patient. Loss of bone mass depends on the activity of the inflammatory process, high levels of bone resorption markers and vitamin D deficiency.

Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.

Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.

Utility of bone turnover markers in metabolic bone diseases

Bone turnover markers (BTMs) are biochemical indicators that provide information about the rate of bone remodeling, which involves the continuous process of bone formation and bone resorption. BTMs are measured in blood or urine samples and are used in the diagnosis, monitoring, and management of various metabolic bone diseases. They aid in the diagnosis of metabolic bone diseases by providing information about the bone turnover status. Abnormal levels of BTMs can indicate increased bone resorption or decreased bone formation, which are characteristic of certain conditions such as osteoporosis, osteomalacia, or Paget's disease. BTMs can provide insights into the severity of metabolic bone diseases. For example, in osteoporosis, elevated levels of bone resorption markers such as C-terminal telopeptide of type I collagen (CTX) or tartrate-resistant acid phosphatase 5b (TRACP-5b) indicate increased bone breakdown and higher fracture risk. Similarly, low levels of bone formation markers like procollagen type I N-terminal propeptide (PINP) or osteocalcin can indicate reduced bone formation and decreased bone strength. BTMs are valuable tools for assessing the response to treatment in metabolic bone diseases. Changes in BTM levels over time can indicate the effectiveness of interventions such as pharmacotherapy, lifestyle modifications, or surgical interventions. Decreased levels of bone resorption markers or increased levels of bone formation markers suggest a positive response to treatment, whereas persistent abnormal BTM levels may indicate the need for treatment adjustment. It's important to note that BTMs should be interpreted in conjunction with other clinical factors and imaging studies. They provide valuable information about bone turnover dynamics but should not be relied upon as standalone diagnostic or prognostic tools.

Sex Differences in Phosphate Homeostasis: Females Excrete More Phosphate and Calcium After an Oral Phosphate Challenge.

Dietary consumption of phosphate is increasing, and elevated serum phosphate is associated with increased cardiovascular disease (CVD) risk. Sex differences in phosphate homeostasis and response to changes in dietary phosphate intake, which are not captured by clinically measured analytes, may contribute to differences in CVD presentation and bone disease. To assess sex differences in acute phosphate homeostasis in response to a single oral phosphate challenge. Cross-sectional. General community. 78 participants (40-76 years) with measured glomerular filtration rate >60 mL/min/1.73 m2 and no clinically diagnosed CVD and 14 young healthy adults. To elucidate subtle alterations in phosphate homeostasis, we employ an acute challenge whereby the hormonal response, circulating mineral levels, and urinary excretion are assessed following an oral challenge of phosphate. Although both males and females had similar changes in circulating phosphate, calcium, and parathyroid hormone in response to the challenge, females excreted ∼1.9x more phosphate and ∼2.7x more calcium than males, despite not consuming calcium. These sex differences were recapitulated in healthy young adults. This excretion response did not correlate to age, serum phosphate, or estradiol levels. The females with greater excretion of phosphate had higher levels of bone resorption markers compared to formation markers. Taken together, these data identify sex differences in acute phosphate homeostasis, specifically that females may mobilize and excrete endogenous sources of calcium and phosphate in response to oral phosphate compared to males. While high levels of dietary phosphate negatively impact bone, our results suggest that females may incur more risk from these diets.

Preparation of chitosan/sodium lignosulfonate/Ag NPs: A potent and green bio-nanocomposite for the treatment of glucocorticoid induced osteoporosis in rats

• CS/NaLS/Ag NPs have antioxidant potentials. • CS/NaLS/Ag NPs have non-cytotoxicity effects. • The results of the CS/NaLS/Ag NPs have revealed that the recent nanocomposite has been formulated as the best. • The treatment of osteoporosis by CS/NaLS/Ag NPs was proven in the recent study. In this study we report the green synthesis of nontoxic, stable, and small size silver nanoparticle by using chitosan/sodium lignosulfonate hydrogel with capping/reducing ability for the synthesis of CS/NaLS/Ag NPs. The prepared bio-nanocomposite were characterized by advanced physicochemical techniques like Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that CS/NaLS/Ag NPs have a spherical shape with a mean diameter from 20 to 30 nm. Administration of CS/NaLS/Ag NPs (5 µg/kg/day, po, for 30 days) and risedronate (20 µg/kg, sc, five times a week for 30 days) following methyl prednisolone sodium succinate (10 mg/kg, sc, thrice a week for 4 weeks) induced osteoporosis in Wistar rats showed an increase in the serum levels of bone mineral content markers and a decrease in serum and urinary levels of bone resorption markers. An incline in strength of femur and tibia was seen particularly with 5 µg/kg of CS/NaLS/Ag NPs. Maintenance of calcium homeostasis, formation of collagen and scavenging of free radicals can plausibly be the mode of action of CS/NaLS/Ag NPs thereby combating osteoporosis induced by glucocorticoids.

Bone regeneration after marginal bone resection in two-stage treatment of chronic long bone infection - a combined histopathological and clinical pilot study

IntroductionIn chronic bone infection, marginal bone resection avoids large and difficult to reconstruct bone defects. However, there is still a lack of knowledge on bone regeneration during chronic bone infection and bone healing capability after marginal bone resection. Therefore, the purpose of this study was to investigate the clinical and histopathological outcomes after marginal bone resection in chronic long bone infection. We hypothesized that there is a regenerative bone healing potential after marginal bone resection that results in an acceptable clinical outcome and improved pathohistological bone healing parameters during treatment. Materials and methodsNine patients were treated for chronic bone infections in a two-stage manner with marginal bone resection of the infected area and the placement of an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage one followed by bone reconstruction at stage two combined with systemic antibiotic therapy. Comparable bone samples were harvested at the border region between vital and necrotic bone area during stage one and the identical location during stage two. Control bone samples were harvested from five healthy patients without bone infection. Clinical outcome in terms of infection eradication and bone consolidation were assessed. The phenotypic changes of osteocyte and morphological changes of lacunar-canalicular network were investigated by histological and immunohistochemical staining between the two observation periods. Furthermore, expression levels of major bone formation and resorption markers were investigated by immunohistochemical and tartrate-resistant acid phosphatase (TRAP) staining. ResultsThe clinical results with a follow-up of 12.9 months showed that eight of nine patients (88.9%) achieved bone consolidation after a planned two-stage procedure of marginal resection of necrotic bone and consecutive reconstruction. In four of the nine patients (44.4%), additional marginal debridements after stage two had to be performed. After marginal resection at stage one, the improved bone formation ability at stage two was demonstrated by significantly lower percentage of empty lacunae, significantly more mature osteocytes and higher BMP-2 positive cell density, whereas decreased resorption was indicated by significantly lower osteoclast density and RANKL/OPG ratio. In patients requiring additional debridement compared to patients without additional debridements, a significantly higher percentage of empty lacunae was found at stage one. ConclusionMarginal bone resection combined with local and systemic antibiotic therapy is a feasible treatment option to avoid large bone defects as bone from the marginal resection area seems to have good regenerative potential. Despite a high revision rate of 44.4%, this technique avoids large bone resection and revisions can be done by further marginal debridements.

Effects of prior osteoporosis treatment on the treatment response of romosozumab followed by denosumab in patients with postmenopausal osteoporosis.

To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis. In this prospective, observational, multicenter study, treatment-naïve patients (Naïve; n = 55) or patients previously treated with bisphosphonates (BP; n = 37), DMAb (DMAb; n = 45) or teriparatide (TPTD; n = 17) (mean age, 74.6years; T-scores of the lumbar spine [LS] - 3.2 and total hip [TH] - 2.6) were switched to ROMO for 12months, followed by DMAb for 12months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24months. A BMD increase was observed at 12 and 24months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (P < 0.001 between the groups at both 12 and 24months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (P < 0.01 between the groups at 12months and P < 0.001 at 24months) in TH, respectively. The BMD increase in LS from 12 to 24months was negatively associated with the levels of bone resorption marker at 24months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%). Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.

Design and synthesis of chitosan/agar/Ag NPs: A potent and green bio-nanocomposite for the treatment of glucocorticoid induced osteoporosis in rats

In this work we have demonstrated the green synthesis of stable and mono-dispersed Ag NPs using chitosan/Agar hydrogel having reducing/stabilizing ability avoiding any toxic reagents. Agarose was used as a green reductant for the synthesis of Ag NPs which gets stabilized by chitosan. The in situ prepared Ag NPs@CS/Agar nano bio-composite were characterized by advanced physicochemical techniques like Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. The Ag NPs encapsulated by CS/Agar bio-composite have a spherical shape with a mean diameter from 10 to 15 nm. Towards its bioapplication, the Ag NPs@CS/Agar nano bio-composite was administered by 5 µg/kg/day for 30 days in comparison to methyl prednisolone sodium succinate by 10 mg/kg, sc, thrice a week for 4 weeks over Wistar rats having glucocortcoid induced osteoporosis. This showed a significant increase in the serum levels of bone mineral content markers and a decrease in serum and urinary levels of bone resorption markers. An inclination in strength of femur and tibia was seen particularly with 5 µg/kg of Ag NPs@CS/Agar nano bio-composite. Maintenance of calcium homeostasis, formation of collagen and scavenging of free radicals can be the plausible mode of action of this bio-nanocomposite thereby combating osteoporosis induced by glucocorticoids.

Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels.

Although musculoskeletal abnormalities have long been described in patients with Noonan syndrome (NS), only a few studies have investigated the bone status of these patients. The aim of this retrospective observational study was to describe the bone health of children with NS. Thirty-five patients with a genetically confirmed diagnosis of NS were enrolled. We analyzed the axial skeleton (lumbar spine) using dual energy X-ray absorptiometry and the appendicular skeleton (hand) with the BoneXpert system. Bone metabolism markers, including mineral homeostasis parameters, serum 25-hydroxy vitamin D (25-OHD) levels and markers of bone formation and resorption were also reported. Compared to the general population, axial and appendicular bone mass was significantly decreased in children with NS (p<0.0001). Serum 25-OHD levels were low in about half of the patients and were negatively correlated with age (r=-0.52; p<0.0001). Patients with NS exhibited reduced bone formation marker levels and increased bone resorption marker levels (p<0.0001). No gender difference or genotype-phenotype correlations were found for the different bone parameters. Muscle mass and, to a lesser extent, serum insulin-like growth factor 1 (IGF-1) levels were independent predictors of whole-body bone mineral content (p<0.0001 for both parameters; adjusted R2=0.97). In conclusion, bone mass is reduced in children with NS and correlates with decreased muscle mass and low serum IGF-1 levels. These data justify addressing all potential threats to bone health including sufficient calcium and vitamin D intake, regular physical exercise, and hormone replacement therapy.