Serum Markers Of Bone Resorption Research Articles

Favorable impact of PD1/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation

BackgroundSkeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment...

Impact of subgingival instrumentation on systemic inflammation and serum bone resorption marker in premenopausal women with periodontitis: a prospective interventional study.

Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Comparing the effects of two different vitamin regimens on bone metabolism for meat ducks at starting phase

Objective Leg problems including lameness and tibial dyschondroplasia (TD) are one of the most important factors affecting health and animal welfare in meat-type poultry, which are considerably impacted by dietary vitamin regimens. The present study was conducted to investigate the effects of dietary vitamin levels on growth performance and tibia quality in 14-d-old meat ducks. Methods One-d-old Cherry Valley meat-type male ducks were allocated to two vitamin regimens for 14 d, which was formulated according to the recommendation of the National Research Council (NRC, 1994) or China Agricultural Industry Standards (NY/T 2122-2012). Each group included 8 replicates with 16 birds per replicate. Results There was no significant difference in the growth performance of ducks, whereas dietary NY/T vitamin supplementation decreased leg abnormalities as compared to the NRC group, along with similar tibia length, perimeter, and the relative weight of tibia. The tibia from the birds that received the NY/T vitamin diet exhibited markedly higher (p < 0.05) ash level, calcium (Ca) content, and bone strength when compared with the bone of NRC vitamin-treated birds. In the tibia proximal end, the increased trabecular area and a number of bone trabeculae were observed in the NY/T vitamin diet (p < 0.05). Moreover, a pronounced increase (p < 0.05) in the serum Ca, alkaline phosphatase activity, and C-terminal cross-linked telopeptide of type I collagen level as the indicators of bone formation were found in NT/T vitamin diet than them in NRC diet. Dietary supplementation with NY/T vitamin regimen also significantly upregulated the relative gene expression of phosphate regulating endopeptidase homolog x linked (Phex), an osteoblastic gene, as compared to the NRC vitamin diet (p < 0.05). However, the concentration of serum bone resorption markers and the transcription of osteoclast-related genes were comparable between the NRC and NY/T vitamin groups (p > 0.05). Conclusion NY/T vitamin diet improved tibia quality and subsequently decreased leg abnormalities in 14-d-old ducks, which was probably linked with the promoted bone formation.

Preventive effect of Total ethanolic extract of Butea monosperma on bone loss in osteopenic rats

Aim: The intent of the study was to assess the bone conserving effect of Butea monosperma total extract (BTE) prepared from the stem-bark, in ovariectomy (Ovx)-induced bone loss in Sprague Dawley (SD) rats.&#x0D; Methods: Sprague-Dawley rats were ovariectomized (Ovx) and BTE treatment with three different doses (100mg, 250mg and 500mg/kg body weight) commenced a day after Ovx and continued for 12 weeks. Skeletal parameters including trabecular and cortical bone microarchitecture, bone mineral density, bone mineral content, biomechanical strength, bone turnover markers (serum procollagen 1 N-terminal propeptide/ P1NP and cross-linked C-telopeptide of type I collagen/CTX-1), new bone formation rate (periosteal bone formation rate and mineral apposition rate), and expression of osteogenic genes were assessed. Estrogenicity of BTE was assessed by studying uterus at the end of the treatments.&#x0D; Results: Ovx rats treated with BTE prevented the alterations in trabecular and cortical microarchitecture, maintained bone mineral density, bone mineral content, and increased bone biomechanical strength in comparison with Ovx rats. Treatment of BTE also enhanced new bone formation rate, increased the serum bone formation marker (P1NP), decreased the serum bone resorption marker (CTX-1), and upregulated the osteogenic genes in bones. BTE was devoid of estrogen-like effect in uterus.&#x0D; Conclusion: BTE protects against Ovx-induced bone loss by inhibiting bone resorption and increasing new bone formation. The most effective bone conserving dose of BTE was 250mg/kg. This study demonstrates the potential of BTE in preventing/delaying osteoporosis development in postmenopausal women.&#x0D; Keywords: Butea total extract, ovariectomy, bone formation, bone mineral density.

Introducing a novel therapeutic supplement for osteoporosis: Remedial, cytotoxicity and antioxidant effects of plant extract green-formulated gold nanoparticles

Osteoporosis means a decrease in bone density, as a result of which bone strength decreases and becomes brittle, which increases the probability of fracture. Osteoporosis usually develops gradually and does not show any symptoms until a fracture occurs. Osteoporosis can occur in any bone of the body, but it is usually seen in the spine, pelvis, wrists, and ribs. Both men and women at any age may be affected by this disease, but according to statistics, the percentage of women suffering from osteoporosis is higher than men, and the probability of this disease increases with age. Recently, the metallic nanoparticles containing plant extracts have been used for the treatment of bone disorders such as osteoporosis. The obtained nanoparticle (Gold nanoparticles green-formulated by Glycine max L seed extract) was characterized by advanced chemical and physical techniques like TEM, FTIR, and SEM. The cytotoxicity effects of gold nanoparticles against normal cell line i.e. HUVEC were assessed. Administration of gold nanoparticles ‎following methyl prednisolone sodium succinate induced osteoporosis in Wistar rats indicated a raise in the bone mineral content markers serum levels and a reduction in bone resorption markers urinary and serum levels. An incline in tibia and femur strength was observed particularly with 5 µg/kg of gold nanoparticles‎. Calcium homeostasis maintenance, collagen formation and free radicals scavenging can plausibly be the gold nanoparticles action mode ‎thereby combating osteoporosis induced by glucocorticoids.

Dual Inhibition of the Wnt Inhibitors DKK1 and Sclerostin Promotes Fracture Healing and Increases the Density and Strength of Uninjured BoneAn Experimental Study in Nonhuman Primates.

Fracture repair involves the reactivation of developmental signaling cascades, including Wnt signaling that stimulates bone formation and bone regeneration. Rodent data indicate that dual inhibition of the Wnt signaling antagonists sclerostin and Dickkopf-1 (DKK1) increases callus bone volume and strength while increasing bone mass systemically. We evaluated the effects of 16 weeks of subcutaneously administered carrier solution (vehicle, VEH), anti-sclerostin antibody (Scl-Ab), anti-DKK1 antibody (DKK1-Ab), or Scl-Ab plus DKK1-Ab combination therapy (COMBO) on ulnar osteotomy healing in nonhuman primates (cynomolgus monkeys; 20 to 22 per group). Scl-Ab and COMBO therapy increased systemic markers of bone formation versus VEH, with COMBO leading to synergistic increases versus Scl-Ab or DKK1-Ab monotherapies. The COMBO and Scl-Ab groups showed reduced serum markers of bone resorption versus VEH. The COMBO and DKK1-Ab groups exhibited greater callus bone mineral density (BMD), torsional stiffness, and torsional rigidity versus VEH. Lumbar vertebrae from the Scl-Ab and COMBO groups showed greater BMD and bone formation rate versus VEH, and the femoral mid-diaphysis of the Scl-Ab and COMBO groups showed greater periosteal and endocortical bone formation rates versus VEH. DKK1-Ab increased BMD and strength at the ulnar osteotomy site, Scl-Ab increased bone formation and BMD at uninjured skeletal sites, and Scl-Ab plus DKK1-Ab combination therapy induced all of these effects, in some cases to a greater degree versus 1 or both monotherapies. These results in nonhuman primates suggest that DKK1 preferentially regulates bone healing while sclerostin preferentially regulates systemic bone mass. Combination therapy with antibodies against sclerostin and DKK1 may offer a promising therapeutic strategy for both fracture treatment and fracture prevention.

Attenuation of Alzheimer’s brain pathology in 5XFAD mice by PTH1-34, a peptide of parathyroid hormone

BackgroundAlzheimer’s disease (AD) and osteoporosis are two distinct diseases but often occur in the same patient. Their relationship remains poorly understood. Studies using Tg2576 AD animal model demonstrate bone deficits, which precede the brain phenotypes by several months, arguing for the independence of bone deficits on brain degeneration and raising a question if the bone deficits contribute to the AD development. To address this question, we investigated the effects of PTH1-34, a peptide of parathyroid hormone analog and a well-recognized effective anabolic therapy drug for patients with osteoporosis, on 5XFAD animal model.Methods5XFAD mice, an early onset β-amyloid (Aβ)-based AD mouse model, were treated with PTH1-34 intermittently [once daily injection of hPTH1–34 (50 μg/Kg), 5 days/week, starting at 2-month old (MO) for 2–3 month]. Wild type mice (C57BL/6) were used as control. The bone phenotypes were examined by microCT and evaluated by measuring serum bone formation and resorption markers. The AD relevant brain pathology (e.g., Aβ and glial activation) and behaviors were assessed by a combination of immunohistochemical staining analysis, western blots, and behavior tests. Additionally, systemic and brain inflammation were evaluated by serum cytokine array, real-time PCR (qPCR), and RNAscope.ResultsA reduced trabecular, but not cortical, bone mass, accompanied with a decrease in bone formation and an increase in bone resorption, was detected in 5XFAD mice at age of 5/6-month old (MO). Upon PTH1-34 treatments, not only these bone deficits but also Aβ-associated brain pathologies, including Aβ and Aβ deposition levels, dystrophic neurites, glial cell activation, and brain inflammatory cytokines, were all diminished; and the cognitive function was improved. Further studies suggest that PTH1-34 acts on not only osteoblasts in the bone but also astrocytes in the brain, suppressing astrocyte senescence and expression of inflammatory cytokines in 5XFAD mice.ConclusionsThese results suggest that PTH1-34 may act as a senolytic-like drug, reducing systemic and brain inflammation and improving cognitive function, and implicate PTH1-34’s therapeutic potential for patients with not only osteoporosis but also AD.

GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells.

Drugs targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) are emerging as treatments for type-2 diabetes and obesity. GIP acutely decreases serum markers of bone resorption and transiently increases bone formation markers in short-term clinical investigations. However, it is unknown whether GIP acts directly on bone cells to mediate these effects. Using a GIPR-specific antagonist, we aimed to assess whether GIP acts directly on primary human osteoclasts and osteoblasts. Osteoclasts were differentiated from human CD14+ monocytes and osteoblasts from human bone. GIPR expression was determined using RNA-seq in primary human osteoclasts and in situ hybridization in human femoral bone. Osteoclastic resorptive activity was assessed using microscopy. GIPR signaling pathways in osteoclasts and osteoblasts were assessed using LANCE cAMP and AlphaLISA phosphorylation assays, intracellular calcium imaging and confocal microscopy. The bioenergetic profile of osteoclasts was evaluated using Seahorse XF-96. GIPR is robustly expressed in mature human osteoclasts. GIP inhibits osteoclastogenesis, delays bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways (Src, cAMP, Akt, p38, Akt, NFκB) to impair nuclear translocation of nuclear factor of activated T cells-1 (NFATc1) and nuclear factor-κB (NFκB). Osteoblasts also expressed GIPR, and GIP improved osteoblast survival. Decreased bone resorption and improved osteoblast survival were also observed after GIP treatment of osteoclast-osteoblast co-cultures. Antagonizing GIPR with GIP(3-30)NH2 abolished the effects of GIP on osteoclasts and osteoblasts. GIP inhibits bone resorption and improves survival of human osteoblasts, indicating that drugs targeting GIPR may impair bone resorption, whilst preserving bone formation.

Serum bone resorption markers and 25-hydroxyvitamin D level in women of the Trans-Baikal region of the Russian and Buryat nationalities

Osteoporosis (OP) is a metabolic bone disease , characterized by a decrease of bone mineral density , leading to the development of low-energy fractures . Serum pyridinoline (PYD) and C- terminal cross-linking telopeptide type I (β- CrossLaps ) are among the specific markers of bone resorption . Vitamin D is involved in the metabolism of bone tissue , its deficiency accelerates the processes of bone tissue breakdown . Material and methods . 60 women with osteoporosis were studied (30 Russian and 30 Buryat nationalities ) aged 50 to 80 years ; the control group included 20 women (10 Russian and 10 Buryat nationalities ). Serum bone resorption markers , namely pyridinoline a nd β- C rossLaps , 25-hydroxyvitamin D (25(OH)D) w ere m easured u sing i mmunoassays . R esults a nd d iscussion . The l evel o f β- C rossLaps w as h igher a nd t he c ontent o f 25(OH)D w as l ower i n w omen w ith o steoporosis c ompared t o t he c ontrol g roup . T here w as a p ositive r elationship b etween β- C rossLaps c oncentration a nd b ody m ass i ndex &lt; 20 k g / cm 2 , f requent f alls , a nd a h ip f racture , b etween t he l evel o f 25(OH)D a nd h ereditary h istory o f o steoporosis i n Russian w omen . T here w as a p ositive r elationship b etween S erum p yridinoline a nd s moking , b etween 25(OH)D a nd l ow p hysical a ctivity , β- C rossLaps a nd t he m ajor o steoporotic f ractures i n B uryat w omen . It w as f ound t hat t he β- C rossLaps i s a n i ndependent p redictor o f t he d evelopment o f f ractures i n Russian w omen (β = 0.678, p = 0.04). In B uryat w omen , i ndependent p redictors o f f ractures a re p yridinoline (β = –0.38, p = 0.04) a nd β- C rossLaps (β = 0.671, p = 0.01). C onclusions . The s ystemic m arkers o f b one r esorption ( p yridinoline , β- C rossLaps ) a nd 25(OH)D c an b e u sed i n t he d iagnosis o f o steoporosis a nd f ractures i n r esidents o f t he Trans- B aikal R egion i n a ddition t o r isk f actor a ssessment a nd b one m ineral d ensity m easurement .

Soy Isoflavones and Bone Health: Focus on the RANKL/RANK/OPG Pathway.

Bone remodels via resorption and formation, two phenomena that continuously occur in bone turnover. The RANKL/RANK/OPG pathway is one of the several mechanisms that affect bone turnover. The RANKL/OPG ratio has a substantial role in bone resorption. An imbalance between formation and resorption is related to an increased RANKL/OPG balance. OPG, a member of this system, can bind to RANKL and suppress RANK-RANKL interaction, and subsequently, inhibit further osteoclastogenesis. The serum levels of RANKL and OPG in the bone microenvironment are vital for osteoclasts formation. The RANK/RANKL/OPG system plays a role in the pathogenesis of bone disorders. This system can be considered a new treatment target for bone disorders. Soy isoflavones affect the RANK/RANKL/OPG system through numerous mechanisms. Soy isoflavones decrease RANKL levels and increase OPG levels. Therefore, isoflavones improve bone metabolism and decrease bone resorption. Soy isoflavones decrease serum markers of bone resorption and improve bone metabolism. However, while the available data are promising, the results of several studies reported no change in RANKL and OPG levels with isoflavones supplementation. In this regard, current evidence is insufficient for conclusive approval of the efficacy of isoflavones on RANKL/RANK/OPG and further research, including animal and human studies, are needed to confirm the effect of soy isoflavones on the RANKL/RANK/OPG pathway. This study was a review of available evidence to determine the role of isoflavones in bone hemostasis and the RANK/RANKL/OPG pathway. The identification of the effects of isoflavones on the RANKL/RANK/OPG pathway directs future studies and leads to the development of effective treatment strategies for bone disorders.

Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones: pilot study

The objective is to evaluate the effect of phytate supplements on calciuria in patients with urinary stones and elevated bone resorption. The secondary objective is to analyze the therapeutic effect of phytate based on measurements of serum markers of bone resorption. This is a controlled randomized study included patients according to predefined inclusion and exclusion criteria, and randomized them into two groups. Patients in the phytate group received a 380 mg capsule of calcium-magnesium InsP6 (Salvat Laboratories®) every 24 h for 3 months and patients in the control group received no treatment. All included patients were male or female, 18–65 years old, had hypercalciuria (> 250 mg/24 h), had a ß-Crosslaps level greater than 0.4 ng/mL, and had bone densitometry results indicative of osteopenia or osteoporosis in the femur and/or spine. At study onset, calciuria was 321 ± 52 mg/24 h in the phytate group and 305 ± 57 mg/24 h in the control group (p > 0.05). At 3 months, calciuria was significantly lower in the phytate group than the control group (226 ± 45 mg/24 h vs. 304 ± 58 mg/24 h, p < 0.05). At study onset, the mean ß-CrossLaps level was 1.25 ± 0.72 ng/mL in the phytate group and 0.57 ± 0.13 ng/mL in the control group (p < 0.05). However, at 3 months, the ß-CrossLaps level was significantly lower in the phytate group than in the control group (0.57 ± 0.13 ng/mL vs. 0.77 ± 0.42 ng/mL, p < 0.05). Phytate reduced calciuria in patients with hypercalciuria secondary to bone resorption. The ß-CrossLaps assay was effective for evaluating the efficacy of phytate on hypercalciuria during follow-up.

The Time of Day for Exercise Does Not Affect the Beneficial Effect of Exercise on Bone Structure in Older Female Rats

Abstract Objectives Bone resorption and formation exhibit diurnal patterns, and disruption of the circadian rhythm affects the balance of bone turnover leading to bone deterioration. This study investigated whether the time of day for exercise alters bone metabolism in a rodent model. We hypothesized that exercise during the active phase results in greater bone mass than exercise during the rest phase in older, female rats. Methods Sixty, female 12-month-old Sprague Dawley rats were randomly assigned to four treatment groups (n = 15/group). Rats were subjected to no exercise or 2 hours of involuntary exercise at 9 meters/minutes and 5 days/week for 15 weeks using motor-driven running wheels at Zeitgeber time (ZT) 4–6 (rest phase), ZT 12–14 (early active phase), or ZT 22–24 (late active phase). ZT 0 is defined as light on, the start of the rest phase. A red lamp was used at minimal intensity during the active, dark phase exercise. Results There were no differences in body weight, fat mass, lean mass, the serum bone resorption marker (C-terminal telopeptide of type 1 collagen), and bone structural parameters among rats exercised at different times. Compared to No-exercise, exercise (combined exercise groups) increased femoral bone volume/total volume, connectivity density, and decreased structural model index (P &amp;lt; 0.05). Exercise also increased trabecular thickness in 2nd lumbar vertebrae. Conclusions These data indicate that exercise is beneficial to bone structure and that the daily time of exercise does not alter the beneficial effect of exercise in older, female rats. Funding Sources Agricultural Research Service of the United States Department of Agriculture, #3062-51,000-053-00D.

PD05-04 EFFECT OF PHYTATE ON HYPERCALCIURIA SECONDARY TO BONE RESORPTION IN PATIENTS WITH URINARY STONES

You have accessJournal of UrologyCME1 May 2022PD05-04 EFFECT OF PHYTATE ON HYPERCALCIURIA SECONDARY TO BONE RESORPTION IN PATIENTS WITH URINARY STONES Jordi Guimera, Ana Martinez Moreno, Jose Luis Bauza Quetglas, Pilar Sanchis Cortes, Enrique Pieras Ayala, and Feliciano Grases Freixedas Jordi GuimeraJordi Guimera More articles by this author , Ana Martinez MorenoAna Martinez Moreno More articles by this author , Jose Luis Bauza QuetglasJose Luis Bauza Quetglas More articles by this author , Pilar Sanchis CortesPilar Sanchis Cortes More articles by this author , Enrique Pieras AyalaEnrique Pieras Ayala More articles by this author , and Feliciano Grases FreixedasFeliciano Grases Freixedas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002524.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hypercalciuria is the most common urinary alteration in patients with kidney stones. Multiple studies reported associations of hypercalciuria with renal lithiasis and elevated bone resorption. Phytate (inositol hexakisphosphate, InsP6) can inhibit kidney stone formation and bone resorption. The main objective of this study is to evaluate the effect of phytate supplements on calciuria in patients with urinary stones and elevated bone resorption. The secondary objective is to analyze the therapeutic effect of phytate based on measurements of serum markers of bone resorption. METHODS: This controlled randomized study enrolled patients according to predefined inclusion and exclusion criteria, and randomized them into two groups. Patients in the phytate group received a 380 mg capsule of calcium-magnesium InsP6 (Broken Laboratories®) every 24 h for 3 months and patients in the control group received no treatment. All included patients were male or female, 18 to 65 years-old, had hypercalciuria (>250 mg/24 h), had a ß-Crosslaps level greater than 0.4 ng/mL, and had bone densitometry results indicative of osteopenia or osteoporosis in the femur and/or spine. The baseline characteristics of patients in both groups were compared using a t-test for independent samples (quantitative data) and a chi-square test or Fisher’s exact test (categorical data). The inter and intragroup comparisons were made using t-test for paired and independent samples and ANCOVA. RESULTS: At study onset, calciuria was 321±52 mg/24 h in the phytate group and 305±57 mg/24 h in the control group (p>0.05). At 3 months, calciuria was significantly lower in the phytate group than the control group (226±45 mg/24 h vs. 304±58 mg/24 h, p<0.05). At study onset, the mean ß-CrossLaps level was 1.25±0.72 ng/mL in the phytate group and 0.57±0.13 ng/mL in the control group (p<0.05). However, at 3 months, the ß-CrossLaps level was significantly lower in the phytate group than in the control group (0.57±0.13 ng/mL vs. 0.77±0.42 ng/mL, p<0.05). Thus, calciuria decreased by 29% (±12) in the phytate group and 0.1% (±14) in the control group B (p<0.05) and the ß-CrossLaps level decreased by 35% (±15) in the phytate group and 0.6% (±14) in the control group (p<0.05). CONCLUSIONS: Phytate reduced calciuria in patients with hypercalciuria secondary to bone resorption. The ß-CrossLaps assay was effective for evaluating the efficacy of phytate on hypercalciuria during follow-up. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e87 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jordi Guimera More articles by this author Ana Martinez Moreno More articles by this author Jose Luis Bauza Quetglas More articles by this author Pilar Sanchis Cortes More articles by this author Enrique Pieras Ayala More articles by this author Feliciano Grases Freixedas More articles by this author Expand All Advertisement PDF DownloadLoading ...

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.

Comparative study of holothurin A and echinoside A on inhibiting the high bone turnover via downregulating PI3K/AKT/β-catenin and OPG/RANKL/NF-κB signaling in ovariectomized mice.

Holothurin A (HA) and Echinoside A (EA) are the most abundant monomers in sea cucumber saponins, exhibiting different structures only in the side chain at position 20. However, although sea cucumber saponins have been proved to have osteogenic activity, the effect and structure-activity relationship of sea cucumber saponins to improve osteoporosis remain unknown. In the current study, mice with ovariectomization-induced osteoporosis were orally administered with HA and EA for 90 days. The result showed that both HA and EA reduced the levels of serum osteogenesis markers ALP, collagen I, and OCN and bone resorption markers MMP-9, Cath-K and TRAP, and thus inhibited the high bone turnover induced by ovariectomy. Furthermore, we found that HA and EA increased the bone mineral density and apposition rate, reversed the loss of trabecular bone and bone marrow stroma, in which EA exhibited more effective effects. CB1 and MKP-1 are the targets of the glucocorticoid-like effect of saponins. PCR and western blot results indicated that HA and EA alleviated overactive osteogenesis via stimulating CB1 and MKP-1, downregulating the PI3K/AKT/β-catenin signal pathway. The OPG/RANKL/NF-κB pathway was identified as a critical regulator of bone resorption. Further investigation revealed that HA and EA significantly downregulate the expression of IKK, NF-κB and phosphorylated NF-κB p65, suppressing the expression of osteoclastogenesis transcription factors c-fos and NFATC1. To the best of our knowledge, this is the first report showing that both HA and EA improved osteoporosis, and these activities depend on the structure of saponins. These findings would provide guidance for the application of saponins in the management of osteoporosis.

Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.

We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats.

In the USA, as many as 20 % of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop Fe deficiency upon completion of training. Fe is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesised Fe deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: Fe-adequate sedentary, Fe-deficient sedentary, Fe-adequate exercise and Fe-deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughnessand tibiae mineral composition and morphometry were measured. Fe deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, Fe deficiency further increased bone TRAcP 5b, while in Fe-adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, Fe deficiency increased the rate of bone formation, mineral apposition and Zn content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by Fe deficiency despite a decrease in tibiae Fe content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

Myeloid Lineage Ablation of Phlpp1 Regulates M-CSF Signaling and Tempers Bone Resorption in Female Mice.

Prior work demonstrated that Phlpp1 deficiency alters trabecular bone mass and enhances M-CSF responsiveness, but the cell types and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within myeloid lineage cells, we crossed Phlpp1 floxed mice with mice harboring LysM-Cre. Micro-computed tomography of the distal femur of 12-week-old mice revealed a 30% increase in bone volume per total volume of Phlpp1 female conditional knockouts, but we did not observe significant changes within male Phlpp1 cKOLysM mice. Bone histomorphmetry of the proximal tibia further revealed that Phlpp1 cKOLysM females exhibited elevated osteoclast numbers, but conversely had reduced levels of serum markers of bone resorption as compared to littermate controls. Osteoblast number and serum markers of bone formation were unchanged. In vitro assays confirmed that Phlpp1 ablation enhanced osteoclast number and area, but limited bone resorption. Additionally, reconstitution with exogenous Phlpp1 suppressed osteoclast numbers. Dose response assays demonstrated that Phlpp1−/− cells are more responsive to M-CSF, but reconstitution with Phlpp1 abrogated this effect. Furthermore, small molecule-mediated Phlpp inhibition enhanced osteoclast numbers and size. Enhanced phosphorylation of Phlpp substrates—including Akt, ERK1/2, and PKCζ—accompanied these observations. In contrast, actin cytoskeleton disruption occurred within Phlpp inhibitor treated osteoclasts. Moreover, Phlpp inhibition reduced resorption of cells cultured on bovine bone slices in vitro. Our results demonstrate that Phlpp1 deficiency within myeloid lineage cells enhances bone mass by limiting bone resorption while leaving osteoclast numbers intact; moreover, we show that Phlpp1 represses osteoclastogenesis and controls responses to M-CSF.