Bone Markers Research Articles

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population.

Bone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Unilateral “Inactive” Condylar Hyperplasia: New Histological Data

Background: Unilateral condylar hyperplasia (UCH) is characterized by slow progression and enlargement of the condyle, accompanied by elongation of the mandibular body, resulting in facial asymmetry, occlusal disharmony, and joint dysfunction. This condition can be defined as “active” or “inactive”: the active form is characterized by continuous growth and dynamic histologic changes, whereas the inactive form indicates that the growth process has stabilized. Since there are few microscopic studies on the inactive form, this study aims to investigate the histological features and expression of key proteins and bone markers in patients diagnosed with inactive UCH. Methods: A total of 15 biopsies from patients aged 28 to 36 years were examined by light microscopy and immunofluorescence for collagen I and II, metalloproteinases 2 (MMP-2) and 9 (MMP-9), receptor activator of nuclear factor- kappa B (RANK), and osteocalcin. Results: Our findings indicate that during inactive UCH, the ongoing process is not entirely stopped, with moderate expression of collagen, metalloproteinases, RANK, and osteocalcin, although no cartilage islands are detectable. Conclusions: The present study shows that even if these features are moderate when compared to active UCH and without cartilage islands, inactive UCH could be characterized by borderline features that could represent an important trigger-point to possible reactivation, or they could represent a long slow progression that is not “self-limited”.

Glycogen Storage Disease Type I and Bone: Clinical and Cellular Characterization.

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable.

Accuracy and precision of Volumetric Matching Micromotion Analysis (V3MA) is similar to RSA for tibial component migration in TKA.

Radiostereometric analysis (RSA) is the current gold standard to determine implant migration, but it requires bone markers and special equipment. Therefore, we developed VoluMetric Matching Micromotion Analysis (V3MA), a software program for Computed Tomography-based radiostereometric analysis (CT-RSA). This study aimed to determine the accuracy and precision of V3MA in vitro compared to RSA and provide a clinical proof of concept. The accuracy (RMSE (Root Mean Squared Error)) and precision (SD (standard deviation)) of V3MA were compared to RSA. A tibial component was placed in 21 different positions within a cadaveric bone to assess accuracy. For precision,a total of 20 repeated zero-migration examinations from 4 cadaveric bones with cemented tibial components were performed. In 6 total knee arthroplasty (TKA) patients 1 to 5 year migration was measured with V3MA and RSA. V3MA accuracy ranged between 0.02 and 0.09 mm for translations and was 0.01° for internal-external rotations. For RSA, the accuracy ranged between 0.03 and 0.09 mm for translations and was 0.09° for internal-external rotations. V3MA precision ranged between 0.01 and 0.06 mm for translations and 0.02 to 0.07° for rotations. RSA precision ranged between 0.00 and 0.06 mm for translations and 0.04 to 0.25° for rotations. V3MA was successful in 6 clinical cases and no systematic bias was present. In conclusion, the accuracy and precision of V3MA were similar to RSA. Therefore, V3MA is a promising alternative to RSA in migration measurements of tibial components in TKA.

Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.

Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of Lal knockout (Lal KO) mice. Both models develop progressive lymphocyte dysfunction and expansion of myeloid-derived suppressor (CD11b+ Gr-1+) cells. To study whether MMP-12 might be a detrimental contributor to the pathology of LAL-D, we have generated Lal/Mmp12 double knockout (DKO) mice. The phenotype of Lal/Mmp12 DKO mice closely resembled that of Lal KO mice, while the weight and morphology of the thymus were improved in Lal/Mmp12 DKO mice. Cytological examination of blood smears showed a mildly reversed lymphoid-to-myeloid shift in DKO mice. Despite significant decreases in CD11b+ Ly6G+ cells in the peripheral blood, bone marrow, and spleen of Lal/Mmp12 DKO mice, the hematopoietic bone marrow progenitor compartment and markers for neutrophil chemotaxis were unchanged. Since the overall severity of LAL-D remains unaffected by the deletion of Mmp12, we conclude that MMP-12 does not represent a viable target for treating the inflammatory pathology in LAL-D.

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

A-049 Effect of Supplementation With Prebiotics on Levels of 25-Hydroxy Vitamin D and on Biomarkers of Bone Remodelling-Results From the OSTEOME Clinical Trial

Abstract Background It is proven that intestinal microbes regulate bone metabolism and can affect the quality of the bone. Prebiotics contain no microorganisms, only substances stimulating their growth. Moreover, flavonoids and catechines are transformed by the microbes into bioactive compounds and polyphenols can modify the microflora composition. OSTEOME is a randomized double-blinded clinical trial to evaluate the efficacy of dietary supplements enriched with prebiotics, in advancing the role of gut microbiota in bone remodelling. We present the effect of supplementation with prebiotics on the serum levels of 25-hydroxy vitamin D (25OHD) and on levels bone markers Osteocalcin (OCN), and C-Terminal Telopeptide of Type-I Collagen (CTX). Methods We enrolled 120 postmenopausal women with osteopenia. Participants were randomized into three groups of 40-participants. Group-A received a supplement containing 600mg calcium citrate and 2400IUof vitamin D3 only, group-B received a supplement additionally containing flavonoids (120mg Naringin and 120mg Hesperidine) and group-C received additionally prebiotic oligosaccharides (2000mg fructooligosaccharides and acacia gum). Blood collections were performed at baseline and at 3, 6 and 9 months for the measurement of bone remodelling biomarkers. Levels of serum Calcium (sCa), 25OHD, as well as levels bone markers OCN, and CTX were measured at all timepoints of follow-up. Results The mean age of group-A, group-B and group-C participants was 60.72(+8.08), 62.37(+7.70) and 62.09(+7.09) (p=NS), and the mean BMIs were 25.35(+3.96), 25.89(+3.80) and 26.25(+4.56) (p=NS). All women were osteopenic as mean total hip T-score was -1.282(+0.617), -1.193(+0.659) and -1.273(+0.573) at baseline for all three groups respectively. The results of OCN, CTX and 25OHD are shown in the table. Conclusions Only patients in group-C showed significant changes in CTX and 25OHD at 9-months, and OCN at 6- and 9-months. Addition of prebiotics to supplements might improve the vitamin D absorption from the gut and give positive balance to biomarkers of bone metabolism.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Umbelliferone reduces inflammation and ligature-induced osteoclastic alveolar bone resorption in mice.

This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1β level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. Periodontitis significantly increased MPO activity, interleukin-1β level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1β level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. UMB improved periodontitis by reducing inflammation and bone markers.

Effect Of Impact During High-intensity Interval Exercise On Bone Markers In Female Adolescents

Effect Of Impact During High-intensity Interval Exercise On Bone Markers In Female Adolescents

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

Antiosteoporosis and bone protective effect of alpinumisoflavone in steroid-induced osteoporosis rats via alteration of apoptosis, inflammatory and RANK/RANKL/OPG signaling pathway

Objective: To estimate the bone protective effect of alpinumisoflavone, a natural prenylated isoflavonoid, against glucocorticoid-induced osteoporosis in rats. Methods: Male Wistar rats received intramuscular administration of dexamethasone (4 mg/mL) at a dose level of 7 mg/kg for 5 weeks, and then alpinumisoflavone (5, 10, and 15 mg/kg) and alendronate (2 mg/kg) from 2 weeks. The body weight and organ weight (femoral, vagina, and uterus) were estimated. MicroCT analysis, bone turnover markers, bone parameters, oxidative stress parameters, and inflammatory cytokines were estimated. mRNA expressions of related genes were also estimated. Results: Alpinumisoflavone remarkably boosted body weight and organ weight (ureters and vagina), improved microCT analysis parameters, and boosted levels of bone markers. Besides, alpinumisoflavone considerably (P<0.001) restored the level of bone turnover markers and oxidative stress parameters, remarkably suppressed the level of cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and increased transforming growth factor-β and insulin-like growth factor. It also significantly restored the osteoprotegerin (OPG, RANKL, and OPG/RANKL ratio) levels and the mRNA expression of Caspase (3, 6, 7, 9), BMPs, OPN, ALP, RUNX2, and OCN. Conclusions: The current result suggests the bone protective effect of alpinumisoflavone against glucocorticoid-induced osteoporosis in rats.

Insights for possible association and impact of thyroidectomy to osteoarthritis

Background and aim of studyThyroidectomy and osteoarthritis have drawn more attention in last decades due to increase various local and systemic risk factors. This study is aimed to determine the association and impact between thyroidectomy and osteoarthritis by serological measurement of most specific related markers.ResultsMeasurement of thyroid markers showed the level of thyroid-stimulating hormone (TSH) was significantly increased, while parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) levels were decreased in osteoarthritis subjected to thyroidectomy group (OTG) when compared to hyperthyroidism subjected to thyroidectomy group (TG), osteoarthritis group (OG), and healthy control group (CG). Detection the activity of bone markers showed the level of R-factor was significantly elevated concomitant with significant reduction in Dickkopf related protein 1 (DKK1), human hyaluronan-binding protein 2 (HABP2), osteocalcin (OC) in OG and OTG groups, while osteopontin (OPN) and procollagen I C-terminal propeptide (PICP) were significantly increased and decreased in TG and OTG. Furthermore, the level of S100 Calcium binding protein (S100CBP) showed significant decreased in patient’s groups, while TG with OTG groups exhibited significant reduction in sclerostin (SOST) concentration. Regarding the inflammatory markers, the levels of interleukin-1 (IL-1) was increased in the OTG, while the level of interleukin-10 (IL-10) was increased in OG and TG groups, and reduced in OTG. While, the level of transforming growth factor-beta (TGF-β) was decreased in OG and TG associated with significant increases in tumor necrosis factor-alpha level (TNF-α) in OTG. Measurement of oxidant and antioxidant activity markers showed the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly reduced in all patient’s groups compared to control, except the level of CAT in TG, whereas, malondialdehyde (MDA) level was increased in OG and OTG patients. Furthermore, the levels of Alkaline phosphatase (ALP), C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were increased in all patient groups compared to control, while fatty acid-binding protein (FABP) level was increased in OTG only.ConclusionThis unique study in Iraq is identified the interaction effect and impact of thyroidectomy to osteoarthritis according to the results that showed various changes and degree of correlation of study biomarkers in all patient groups, however more depth of specific quantitative and qualitative studies are required to support this association and the impact claim at molecular level.

Elevated Bone Turnover Markers After One Infusion Of Zoledronic Acid Post Denosumab Cessation

Abstract Background Denosumab is a commonly used to treat osteoporosis though should not be stopped without transitioning to bisphosphonates to reduce the risk of rebound bone loss and fracture. Recent NOGG guidelines recommend IV zoledronic acid (ZA) six months after the last denosumab injection with further infusions based on bone turnover markers (BTM). Methods We collated data (over the past 5 years) on the first follow up BTM measured after zoledronic acid treatment given to patients where denosumab was stopped. ZA was administered between 6-7 months after the last denosumab injection. The bone resorption marker (C-Telopeptide type I collagen, CTX ng/ml) was measured at different time points: 4 months, 4-6 months, and between 6-12 months. A subtherapeutic CTX was defined as > 0.300 ng/ml. Results There were 95 patients, 93% female, mean age 67.8 years and duration of denosumab therapy 4.6 years. Bone markers were significantly elevated from baseline at all timepoints. Mean CTX at 4 months was 0.450, 6 months 0.470 and 6-12 months 0.65. Overall, 45% had a subtherapeutic CTX at 4 months, 45% at 6 months and 70% between 6-12 (mean 9 months) and this was predicted by time from first ZA infusion (P=0.03). Conclusion Nearly half of patients had subtherapeutic BTM at 4-6 months and the majority at 6-12 months after receiving ZA. For patients on denosumab therapy for a similar duration (4-5 years), our results support the routine administration of a second ZA six months after their first ZA. Delays in administering a second infusion may result in a substantial rise in bone resorption markers and significant bone loss. This highlights the need for timely access to ZA for such patients transitioning off denosumab therapy.

NIR Laser Irradiation Promotes Osteogenic Differentiation of PDLSCs Through the Activation of TRPV1 Channels and Subsequent Calcium Signaling.

Near-infrared (NIR) irradiation has shown potential to stimulate osteogenic differentiation, but the mechanisms are not fully understood. The study is to investigate the effects of NIR laser irradiation on osteoblastic differentiation. Human periodontal ligament stem cells (hPDLSCs) were cultured in osteogenic medium and exposed to 810 nm NIR laser at 0.5 J/cm2 every 48 h. The transient receptor potential vanilloid (TRPV1) channel inhibitor capsazepine (CPZ) was used to evaluate the role of calcium influx. Osteogenic differentiation was assessed by proliferation (CCK-8), alkaline phosphatase (ALP) activity, mineralization (Alizarin Red), and expression of bone markers by PCR and Western blot over 2 weeks. Intracellular calcium was measured by Fluo-4M dye and flow cytometry. Results showed that NIR irradiation enhanced hPDLSC proliferation, ALP activity, mineralization, and bone marker expression, indicating increased osteogenic differentiation. These effects were inhibited by CPZ. NIR induced a transient rise in intracellular calcium peaking at 3 min, which was blocked by CPZ. In conclusion, this study demonstrates that NIR laser irradiation promotes osteogenic differentiation of PDLSCs through the activation of TRPV1 channels and subsequent calcium signaling. Further research is warranted to optimize the treatment parameters and elucidate the detailed signaling pathways involved, paving the way for the clinical application of NIR therapy in the treatment of bone disorders and periodontal disease.

Longitudinal Analysis of Bone Metabolic Markers and Bone Mechanical Properties in STZ-Induced Diabetic Rats.

Background: This longitudinal study examined the early effects of type 1 diabetes on bone mechanical properties and metabolic markers in mature rats, focusing on the natural progression of diabetes-induced changes without external treatments. Methods: Forty-eight 8-month-old male Wistar rats were divided into two groups, with one group receiving a single dose of streptozotocin (STZ, 60 mg/kg). Assessments were performed 2, 4, and 8 weeks post-administration, including serum biochemical analyses, bone marker assessments, and mechanical bone tests. The data were analyzed using two-way ANOVA to evaluate the impact of time and treatment. Results: At 2 weeks, diabetic rats showed increased fasting blood glucose (p < 0.001), decreased insulin levels (p = 0.03), and changes in HOMA markers (p < 0.001), liver enzymes (p < 0.001), inflammatory markers (p < 0.001), and bone metabolism markers (osteocalcin (p < 0.001), OPG (p = 0.006), RANKL (p < 0.001), and OPG/RANKL ratio (p < 0.001)), with initial alterations in bone geometry. By week 4, decreased body weight in the diabetic group (p < 0.001) led to further changes in bone geometry and initial differences in mechanical properties. At 8 weeks, significant declines in body (p < 0.001) and bone (p < 0.001) weights were observed, along with further deterioration in bone geometry and mechanical properties. Conclusions: The study highlights the significant impact of STZ-induced diabetes on bone health as early as two weeks post-STZ administration, with marked temporal changes in biochemical markers and mechanical properties.

The Impact of Modern Bone Markers in Multiple Myeloma: Prospective Analyses Pre and Post-First Line Treatment.

Multiple myeloma, the disease characterized by the malignant proliferation of plasma cells that invades the bone marrow, produces osteolytic lesions and secretes monoclonal proteins. Several biomarkers have been shown to represent important tools in the pathogenesis of myeloma and offer insights into bone degradation and formation. The objectives of this current study were to assess the associations of modern biomarkers (TNF-α: tumor necrosis factor; IFN: Interferon; FreeRANKL: Free Receptor Activator for Nuclear Factor kappa B Ligand; RANKL: Receptor Activator for Nuclear Factor kappa B Ligand, Beta crosslaps, IL-6: Interleukin 6) with osteolytic lesions status after first-line treatment and to evaluate the correlations between modern and classical biomarkers (LDH: Lactate Dehydrogenase; VSH: Erythrocyte Sedimentation Rate; Hgb: Hemoglobin, Calcium, Albumin, B2microglobulin) stratified by osteolytic lesions status. A total of 35 patients diagnosed with multiple myeloma divided into two groups according to the osteolytic bone lesions, were studied: (1) unchanged status of osteolytic lesions and (2) changed status of osteolytic lesions. After fist-line treatment, we found a significant difference in Albumin (p = 0.0029) and Calcium levels (p = 0.0304), patients with a changed status in osteolytic lesions having higher values of Albumin and Calcium compared to those without changes in status of osteolytic lesions. After first-line treatment, decreased IL-6 values were significantly correlated with elevated values of Albumin (ρ = -0.96, p = 0.0005) in the patients with changed status of osteolytic lesions. Post-treatment values of IFN showed a significant positive correlation with Hemoglobin (ρ = 0.47, p = 0.0124), IL-6 (ρ = 0.55, p = 0.0026) and TNF-alpha values (ρ = 0.54, p = 0.0029). The results obtained from patients with unmodified lytic lesions identified a significant correlation between the biomarkers IL-6, Free RANKL, and IFN-beta with the classical marker LDH. This association highlights the involvement of these markers in promoting bone destruction and the development of osteolytic lesions.

Effects of cluster set resistance training on bone mineral density and markers of bone metabolism in older hemodialysis subjects: A pilot study

Chronic kidney disease (CKD) is associated with a series of mineral bone disturbances due to increased production of parathormone which increases the activity of osteoclasts, removing calcium and phosphorous from the bones. However, the literature lacks investigations on the feasibility of different resistance training (RT) methods, such as cluster-sets, in this population. Thus, the aim of the present study was to compare traditional versus cluster-set RT protocols on bone mineral density (BMD) T-score, BMD Total, femur BMD, L3-L4 BMD, femoral neck BMD, Klotho, FGF23, Klotho - FGF23 ratio, Sclerostin, vitamin D, phosphorous and calcium in older subjects with CKD. Seventy-eight older subjects (age: 57.55 ± 4.06 years, body mass: 72.26 ± 13.96 kg, body mass index: 26.73 ± 2.97 kg/m2) with CKD undergoing maintenance hemodialysis were randomly divided into control group (CG, n = 26), traditional RT (RT, n = 26) and cluster-set RT (RT-CS, n = 26) groups. Subjects completed 24 weeks of RT three times per week, 1 h and 30 min before the hemodialysis session, and each training lasted around 60 to 80 min. There was a group×time interaction for total BMD, femur BMD, L3-L4 BMD, and femoral neck BMD, revealed by improvements for RT and RT-CS groups (pre versus post). Only femur BMD displayed differences as compared with the CG. Minimum clinically important difference (MCID) values revealed more responsive subjects in the RT-CS group for total BMD, femur BMD, klotho, FGF23, sclerostin, Vitamin D and calcium. In conclusion, RT can be used as a non-pharmacological complementary strategy for the treatment of CKD. RT-CS may be useful for these subjects as more responders were found for this type of training.

Differences in Bone Metabolism between Children with Prader-Willi Syndrome during Growth Hormone Treatment and Healthy Subjects: A Pilot Study.

Despite therapy with growth hormone (GH) in children with Prader-Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children (p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower (p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls (p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC (p = 0.013), Gla-OC (p = 0.042), and the OC/CTX-I ratio (p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research.

Bone Turnover Markers during Growth Hormone Therapy for Short Stature Children Born Small for Gestational Age.

Growth hormone therapy (GHT) can improve growth velocity and final height, but can also accelerate the process of bone growth, which is related to structural bone modeling in both formation and resorption. This study evaluated the capacity of bone turnover markers to predict early growth response to one year of GHT in short stature children born small for gestational age (SGA). This study included 25 prepubertal children born SGA. We estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type 1), P3NP (N-terminal procollagen type 3), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA (electrochemiluminescence), RIA (radioimmunoassay), and ELISA (enzyme-linked immunosorbent assay) methods. A statistically significant increase in bone resorption markers (CTX) was found at both 6 and 12 months. P1NP bone markers were increased at 6 months and after 12 months of therapy. The P3NP marker for collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months, and similar ALP (alkaline phosphatase) increases. We found a significant correlation between height (cm) and CTX after 6-12 months, as well as a P1NP/height (SD) correlation after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We found strong reactions of bone resorption and bone formation markers during growth hormone therapy, which may determine their selection as predictors of GHT outcome in children born SGA. However, the issue requires further research.