Changes In Bone Metabolism Research Articles

Bone microstructure and metabolism changes under the combined intervention of ketogenic diet with intermittent fasting: an in vivo study of rats.

Ketogenic diet (KD) has been used in epilepsy for decades, but previous studies found it may cause severe bone loss. Every-other-day ketogenic diet (EODKD), the combination of KD with intermittent fasting, showed better potential for seizure control recently, while its effects on bone remain unknown. This study aims to establish different ketogenic rat models and compare the influence of EODKD with KD on bone microstructure and metabolism. Thirty male Sprague-Dawley rats were divided into Control, KD and EODKD groups, fed with standard diet, continuous and intermittent ketogenic diet respectively. After 12 weeks, bone mineral density (BMD) and body fat percentage were obtained by dual energy X-ray absorptiometry. Micro-CT and three-point bending test were used to evaluate the bone microstructure and mechanical properties. Activities of serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) were measured, together with the osteogenic capabilities of bone marrow stromal cells (BMSCs) tested by ALP activities and alizarin red stain in different osteogenic stage. Both EODKD and KD induced higher ketone and more fat percentage, but led to lower body weight compared with Control group. They both compromised bone mass and mechanical properties. Compared with KD, EODKD demonstrated higher ketone levels, but it also inhibited osteoclastic process as well as early osteogenic differentiation. In general, EODKD accelerated ketosis, but may not deteriorate bone microstructure and strength than KD.

Roux-en-Why? What the Orthopaedic Surgeon Needs to Know About Bariatric Surgery.

* Bariatric surgical procedures can be subdivided into restrictive, malabsorptive, and restrictive and malabsorptive categories.* The greatest amount of excess weight loss occurs by 18 to 24 months following these procedures and can exceed 70% in certain procedures.* Postoperative malabsorption of fat-soluble vitamins and protein is most common in patients with combined restrictive and malabsorptive procedures such as biliopancreatic diversion.* Patients undergoing a bariatric surgical procedure are at an increased risk of fracture due to changes in bone metabolism, with the potential risk for decreased fracture-healing that has not been extensively studied.* Regardless of the improvement in body mass index, patients undergoing a bariatric surgical procedure appear to remain at higher risk for complications with total joint arthroplasty when compared with the general population.

Efektivitas Etelcalcitide terhadap Hiperparatiroidisme Sekunder Pada Pasien Gagal Ginjal Kronik

<p>Secondary hyperparathyroidism (sHPT) is a frequently occurring severe complication of<br />advanced kidney disease. Its clinical consequences include extraskeletal vascular and valvular calcifications, changes in bone metabolism resulting in renal osteodystrophy, and an increased risk of cardiovascular morbidity and mortality. Calcimimetics are a cornerstone of parathyroid hormone (PTH)-lowering therapy, as confirmed by the recently updated 2017 Kidney Disease: Improving Global Outcomes chronic kidney disease – mineral and bone disorder clinical practice guidelines. Contrary to calcitriol or other vitamin D-receptor activators, calcimimetics reduce PTH without increasing serumcalcium, phosphorus,<br />or FGF23 levels. Etelcalcetide is a new second-generation calcimimetic that has been approved for the treatment of sHPT in adult hemodialysis patients. Where as the first-generation calcimimetic cinacalcet is taken orally once daily, etelcalcetide is given intravenously thrice weekly at the end of the hemodialysis session. Apart from improving drug adherence, etelcalcetide has proven to be more effective in lowering PTH when compared to cinacalcet, with an acceptable and comparable safety profile. The hope for better gastrointestinal tolerance with intravenous administration is no true, as etelcalcetide isn’t significantly mitigate the adverse gastrointestinal effects associated with cinacalcet. Enhanced adherence and strong reductions in PTH, phosphorus, and FGF23 can set the stage for a future large randomized controlled trial to demonstrate that improve biochemical control of mineral metabolism with etelcalcetide in hemodialysis patients translates into cardiovascular and survival benefits and better health-related quality of life.</p>

MicroRNA and Human Bone Health.

ABSTRACTThe small non‐coding microRNAs (miRNAs) are post‐transcription regulators that modulate diverse cellular process in bone cells. Because optimal miRNA targeting is essential for their function, single‐nucleotide polymorphisms (SNPs) within or proximal to the loci of miRNA (miR‐SNPs) or mRNA (PolymiRTS) could potentially disrupt the miRNA‐mRNA interaction, leading to changes in bone metabolism and osteoporosis. Recent human studies of skeletal traits using miRNA profiling, genomewide association studies, and functional studies started to decipher the complex miRNA regulatory network. These studies have indicated that miRNAs may be a promising bone marker. This review focuses on human miRNA studies on bone traits and discusses how genetic variants affect bone metabolic pathways. Major ex vivo investigations using human samples supported with animal and in vitro models have shed light on the mechanistic role of miRNAs. Furthermore, studying the miRNAs’ signatures in secondary osteoporosis and osteoporotic medications such as teriparatide (TPTD) and denosumab (DMab) have provided valuable insight into clinical management of the disease. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research

PET-MRI for the Study of Metabolic Bone Disease.

This review article attempts to summarize the current state and applications of the hybrid imaging modality of PET-MRI to metabolic bone diseases. The advances of PET and MRI are also discussed for metabolic bone diseases as potentially applied via PET-MRI. Etiologies and mechanisms of metabolic bone disease can be complex where molecular changes precede structural changes. Although PET-MRI has yet to be applied directly to metabolic bone disease, possible applications exist since PET, specifically 18F-NaF PET, can quantitatively track changes in bone metabolism and is useful for assessing treatment, while MRI can give detailed information on bone water concentration, porosity, and architecture through novel techniques such as UTE and ZTE MRI. Earlier detection and further understanding of metabolic bone disease via PET and MRI could lead to better treatment and prevention. More research using this modality is needed to further understand how it can be implemented in this realm.

Siglec-15-targeting therapy increases bone mass in rats without impairing skeletal growth.

The treatment of juvenile osteoporosis has not been established due to a lack of data regarding the efficacy and adverse effects of therapeutic agents. The possible adverse effects of the long-term use of antiresorptive therapies on skeletal growth in children is of particular concern. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption, and its deficiency suppresses bone remodeling in the secondary spongiosa, but not in the primary spongiosa, due to a compensatory mechanism of osteoclastogenesis. This prompted us to develop an anti-Siglec-15 therapy for juvenile osteoporosis because most anti-resorptive drugs have potential adverse effects on skeletal growth. Using growing rats, we investigated the effects of an anti-Siglec-15 neutralizing antibody (Ab) on systemic bone metabolism and skeletal growth, comparing this drug to bisphosphonate, a first-line treatment for osteoporosis. Male 6-week-old F344/Jcl rats were randomized into six groups: control (PBS twice per week), anti-Siglec-15 Ab (0.25, 1, or 4 mg/kg every 3 weeks), and alendronate (ALN) (0.028 or 0.14 mg/kg twice per week). Treatment commenced at 6 weeks of age and continued for the next 6 weeks. Changes in bone mass, bone metabolism, bone strength, and skeletal growth during treatment were analyzed. Both anti-Siglec-15 therapy and ALN increased bone mass and the mechanical strength of both the femora and lumbar spines in a dose-dependent manner. Anti-Siglec-15 therapy did not have a significant effect on skeletal growth as evidenced by micro-CT-based measurements of femoral length and histology, whereas high-dose ALN resulted in growth retardation with histological abnormalities in the growth plates of femurs. This unique property of the anti-Siglec-15 Ab can probably be attributed to compensatory signaling for Siglec-15 inhibition in the primary spongiosa, but not in the secondary spongiosa. Thus, anti-Siglec-15 therapy could be a safe and effective for juvenile osteoporosis.

Effects of Ultra-early Hyperbaric Oxygen Therapy on Femoral Calcitonin Gene-Related Peptide and Bone Metabolism of Rats With Complete Spinal Transection.

Seventy-five Sprague-Dawley rats were randomly divided into sham, complete spinal cord transection (CSCT) and hyperbaric oxygen (HBO) groups. Among them, rats in HBO group were further divided into 3 hours group (HBO1) and 12 hours group (HBO2). To study the effects of ultra-early HBO therapy on femoral calcitonin gene-related peptide (CGRP) and bone metabolism of rats with CSCT. Complete spinal cord injury (SCI) is still an unresolved problem in clinical practice. Studies on changes in (calcitonin gene-related peptide) CGRP and bone metabolism and osteoporosis prevention after SCI have important clinical significance. Rats in the sham group underwent laminectomy alone, whereas rats in the other three groups underwent laminectomy and CSCT at the level of the 10th thoracic vertebra. Six weeks after operation, rat blood samples and femoral samples from CSCT area were taken and prepared for immunohistochemical staining of CGRP, quantitative polymerase chain reaction (qPCR) of CGRP mRNA, enzyme-linked immunosorbent assay (ELISA) for the levels of serum bone-specific alkaline phosphatase (sBAP), serum osteocalcin (sOC), serum type-I collagen amino-terminal peptide (sNTX), and urinary deoxypyridinoline (uDPD). These data were statistically analyzed using paired LSD or Tamhane. The number of CGRP-positive cells and expression of CGRP mRNA in femur were significantly reduced, and the levels of sBAP, sOC, sNTX, and uDPD were significantly increased in CSCT, HBO1, and HBO2 groups than in the sham group, (P < 0.05-0.01). In addition, the number of CGRP-positive cells, expression of CGRP mRNA in femur, and the levels of sBAP and sOC were significantly enhanced, but the levels of sNTX and uDPD were significantly lowered in HBO1 group than in HBO2 and CSCT groups (P < 0.05). Ultra-early HBO therapy could improve bone turnover, promote bone formation, and prohibit bone resorption by enhancing CGRP synthesis in the sensory neurons in posterior horn of spinal cord. N/A.

Significant Bone Loss in Obese Patients with Acanthosis Nigricans after LSG—One-Year Follow-Up Study

The aim of the study was to investigate the longitudinal bone mineral density(BMD) and bone metabolic related markers changes in obese patients with acanthosis nigricans (AN) and without AN(OB) after Laroscopic Sleeve Gastrectomy (LSG). 41 obese patients (AN group:n=29,OB group:n=12) were recruited in this study. Areal BMD (aBMD) and lumbar spine volumetric BMD (vBMD)were measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Insulin and markers of bone metabolism including 25-OHD, calcium, intact parathyroid hormone (iPTH), osteocalcin (OC), and type I collagen cross-linked C-terminal telopeptide (CTX) ] were assessed; Insulin area under the curve(AUCins) and HOMA-IR were computed. Results showed that the AN group had a higher fasting serum insulin (42.80±28.52 vs. 22.55±8.94mU/L,p=0.006), AUCins (522.42±280.32 vs. 263.87±195.75mU/L,p=0.008)and BMI(40.6±5.1 vs. 36.7±4.1kg/m2,p=0.024) compared to the OB group at baseline. The both groups did a obvious decrease in HOMA-IR after LSG; In AN group, there was a significant decrease in Lumbar vBMD(-4.4%,p=0.011), pelvic aBMD (-6.48%,p&amp;lt;0.001) and femoral neck aBMD (-6.7%,p=0.045) after LSG compared with baseline, whereas no detectable BMD changes in the OB group. CTX and OC increased in both AN (97.69%,79.65%,respectively)and OB(115.21%,62.28%,respectively) groups; No significant alteration of 25-OHD, serum calcium, or iPTH was observed. In conclusion, Insulin resistance was improved, and bone turnover was activated one year after LSG in both groups, but the bone loss was more likely to occur in the obese patients with acanthosis nigricans. Disclosure Y. Zhang: None. Z. Zhang: None. C. Zhu: None. S. Sun: None. Y. Yin: None. R. Cui: None. H. Sheng: None. S. Qu: None.

Changes in body composition, bone metabolism, strength, and skill-specific performance resulting from 16-weeks of HIFT.

High Intensity Functional Training (HIFT) is a training modality, characterized by multimodal exercises performed at high-intensity. Little is known about the training adaptations that occur as a prolonged training program. The purpose of this study was to examine changes in body composition, bone metabolism, strength, and skill-specific performance over 16-weeks of HIFT. Twenty-six recreationally active adult males (n = 9; 34.2 ± 9.1 y; 91.5 ± 17.7 kg; 178.5 ± 5.4 cm) and females (n = 17 = 36.4 ± 7.9 y; 91.5 ± 17.7 kg; 162.9 ± 7.0 cm) completed pre and post training assessments of body composition (Dual-Energy X-Ray Absorptiometry) and performance measures. Performance was assessed using three HIFT workouts (WOD 1–3) to assess strength, skill, and metabolic performance. Aside from the body composition measurements, all assessments were carried out at the local training facility. Training included participation in HIFT a minimum of twice a week for 16-weeks. Repeated measures analysis of variance revealed a significant gender x time interaction in Bone Mineral Content (BMC) (p = 0.027), where improvements favored women (1.0% ± 1.1%, p = 0.004) over men (-0.1% + 0.8%, p = 0.625). Further, region-specific analysis indicated that women (2.5% ± 3.0%, p < 0.005) experienced greater improvements in the trunk compared to men (-0.3% ± 1.8%, p = 0.621), while changes in leg BMC were comparable between women (0.8% ± 1.0%, p < 0.001) and men (0.3% ± 0.6%, p < 0.001). Although no other interactions were observed, significant performance improvements were noted for all participants in WOD 1 (18.3% ± 16.8%), absolute 5RM (14.4% ± 9.7%), relative 5RM (15.4% ± 9.2%), WOD 2 (5.7% ± 6.5%), and WOD 3 (–17.3% ± 14.7%). These data indicate that 16-weeks of HIFT resulted in positive outcomes in strength, metabolic conditioning performance, and body composition.

Role of etelcalcetide in the management of secondary hyperparathyroidism in hemodialysis patients: a review on current data and place in therapy.

Secondary hyperparathyroidism (sHPT) is a frequently occurring severe complication of advanced kidney disease. Its clinical consequences include extraskeletal vascular and valvular calcifications, changes in bone metabolism resulting in renal osteodystrophy, and an increased risk of cardiovascular morbidity and mortality. Calcimimetics are a cornerstone of parathyroid hormone (PTH)-lowering therapy, as confirmed by the recently updated 2017 Kidney Disease: Improving Global Outcomes chronic kidney disease – mineral and bone disorder clinical practice guidelines. Contrary to calcitriol or other vitamin D-receptor activators, calcimimetics reduce PTH without increasing serum-calcium, phosphorus, or FGF23 levels. Etelcalcetide is a new second-generation calcimimetic that has been approved for the treatment of sHPT in adult hemodialysis patients. Whereas the first-generation calcimimetic cinacalcet is taken orally once daily, etelcalcetide is given intravenously thrice weekly at the end of the hemodialysis session. Apart from improving drug adherence, etelcalcetide has proven to be more effective in lowering PTH when compared to cinacalcet, with an acceptable and comparable safety profile. The hope for better gastrointestinal tolerance with intravenous administration did not come true, as etelcalcetide did not significantly mitigate the adverse gastrointestinal effects associated with cinacalcet. Enhanced adherence and strong reductions in PTH, phosphorus, and FGF23 could set the stage for a future large randomized controlled trial to demonstrate that improved biochemical control of mineral metabolism with etelcalcetide in hemodialysis patients translates into cardiovascular and survival benefits and better health-related quality of life.

Changes in bone metabolism after gastric cancer surgery: A prospective observational study.

Changes in bone metabolism after gastric cancer surgery: A prospective observational study.

Calcium homeostasis during pregnancy and lactation: role of vitamin D supplementation

Pregnancy and lactation cycle is a period of considerable strain on maternal calcium homeostasis. A number of adaptive mechanisms involve increased intestinal calcium absorption, renal calcium conservation and changes in bone metabolism. These adaptations are mediated through changes in the secretion of various calciotropic hormones [1,25(OH)2 D3, parathormone, and calcitonin]. In all of these adaptive mechanisms, vitamin D is involved directly or indirectly. Now, it is being realized that not only darkskinned but also even Caucasian women tend to go into vitamin D deficiency during pregnancy. Adverse health outcomes such as preeclampsia, low birth-weight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Vitamin D deficiency seems to be a public health problem even in 2018. Most of the experts in the field are convinced that women need extra amounts of vitamin D during pregnancy and lactation. The amount of vitamin D that is required for optimum calcium homeostasis in this phase of life is still controversial. Studies are under way to establish the recommended daily doses of vitamin D in pregnant and lactating women. Key words : Vitamin D deficiency; Pregnancy; Lactation; Vitamin D supplementation

Longitudinal changes in bone and mineral metabolism after cessation of cinacalcet in dialysis patients with secondary hyperparathyroidism

BackgroundThe calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease.MethodsDialysis patients from a single center who ceased cinacalcet between August 2015 and March 2016 were included in a prospective observational study. Bloods were taken at the time of cessation of cinacalcet and at 1, 6 and 12 months. Clinical and biochemical outcomes were compared with an age- and gender-matched cohort of cinacalcet-naïve dialysis patients.ResultsSixty-two patients participated in the study. Mean age was 69.6 ± 13.2 years. Biochemical changes over 12 months following cessation of cinacalcet included an increase in serum parathyroid hormone (PTH) (42.2 [IQR 27.8–94.6] pmol/L to 114.8 [83.9–159.1] pmol/L [p < 0.001]), serum calcium (2.31 ± 0.21 mmol/L to 2.46 ± 0.14 mmol/L [p < 0.001]) and primary CPP (CPP-I) (p = 0.002). Changes in CPP were associated with an increase in PTH (p = 0.007), calcium (p = 0.002) and ferritin (p = 0.02) but a reduction in serum albumin (p = 0.001). Over the 12-month period, there were two fractures, five cardiovascular events, one episode of calciphylaxis, and one parathyroidectomy, with a mortality rate of 19% (n = 13).ConclusionUniquely we report the effects of cinacalcet withdrawal in a real world setting with demonstrated increases in PTH, serum calcium and CPP subsets, novel CKD-MBD related factors, over a 12-month period.

Changes in bone metabolism after gastric cancer surgery in male patients: a prospective observational study.

Several retrospective studies have shown that bone disorders occur after gastric cancer surgery. This study was designed to prospectively evaluate the changes in bone metabolism after gastrectomy for gastric cancer. We prospectively enrolled 39 men with early gastric cancer who underwent gastrectomy. We excluded women to avoid the effects of menopause. We employed dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) of the lumbar spine. DEXA was performed before and 1 and 2years after surgery. The serum levels of alkaline phosphatase (ALP), 1,25-dihydroxy vitamin D [1,25(OH)2VD], 25-hydroxy vitamin D [25(OH)VD], and estradiol were measured before surgery and every 3months until 2years after surgery. DEXA revealed that BMD significantly decreased by 0.036 ± 0.033g/cm2 12months after gastrectomy (P < 0.001) and by 0.046 ± 0.040g/cm2 24months after gastrectomy (P < 0.001). The serum ALP level significantly increased by 38.31 ± 103.8IU/L 24months after surgery (P = 0.013). The serum 25(OH)VD level significantly decreased by 4.88 ± 6.42ng/ml 24months after surgery (P < 0.001), whereas the serum 1,25(OH)2VD levels were consistently in the normal range. The serum estradiol level significantly increased by 2.94 ± 7.49pg/ml 12months after gastrectomy (P = 0.035). A lower preoperative body mass index (BMI) significantly correlated with the reduction in BMD 12months after surgery; the correlation coefficient was 0.37 (P = 0.025). This study showed that a significant decrease in BMD was observed for up to 24months after gastrectomy, not only 12months.

Midfemoral Bone Volume of Walking Subjects with Chronic Hemiparesis Post Stroke

Muscle and bone form a functional unit. Residual physical poststroke impairments such as muscle weakness, spasticity, and decrease in function can promote metabolic bone changes. Moreover, muscle strength can influence this process. Thus, the purpose of the present study was to investigate bone volume and mobility performance in subjects with chronic hemiparesis post stroke. A cross-sectional study was performed on 14 subjects post stroke who were paired with healthy controls. Bone volume, isometric muscle performance, and mobility levels were measured. Midfemoral bone volumes were determined using magnetic resonance imaging, and muscular performance was measured by dynamometry. Mobility was measured using the Timed Up and Go Test and the 10-Meter Walk Test. Regarding bone volume total, there was no difference in the medullary and cortical groups (P ≥ .05). During torque peak isometric flexion, the paretic group was significantly different compared with the other groups (P = .001). However, the control presented no difference compared with the nonparetic limb (P = .40). With regard to the extension isometric torque peak, the paretic limb was significantly different compared with the nonparetic (P = .033) and the control (P = .001) limbs, and the control was different from the nonparetic limb (P = .045). Bone volume variables correlated with the isometric torque peak. Chronic hemiparetic subjects maintain bone geometry compared with healthy volunteers matched by age, body mass index, and gender. The correlation between bone volume midfemoral structures and knee isometric torque was possible.

Quantitative imaging of bone–cartilage interactions in ACL-injured patients with PET–MRI

To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees. Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes. Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r=0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P<0.001], with a slope of 0.49ms/a.u. This correlation and slope were higher in deep layers (r=0.73, slope=0.60ms/a.u.) of cartilage compared to superficial layers (r=0.40, slope=0.43ms/a.u.). 18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

Остеосцинтиграфия И ОФЭКТ/КТ в диагностике различных вариантов метастатического поражения костей

Purpose: To determine the diagnostic capabilities of body scan (BS) and SPECT/CT in the diagnosis of various variants of bone metastases (BM). Material and methods: The data of 37 patients with BM of breast cancer (20 patients), prostate cancer (7 patients) and other tumors various localization (10 patients) were analyzed. The study was carried out in two stages: first, BS was performed, 3 hours after intravenous introduction of an osteotropic radiopharmaceutical labeled with 99mTc (technephor or phosphotech), followed by SPECT/CT of the selected zone of interest. All studies were performed on a combined system Symbia T2 (Siemens) with a 2-slice low dose CT. Results: With BS the foci of the tumor lesion were identified in 33 cases, and in SPECT/CT in 37 cases. There were detected 159 BM (21 sites: 0.4–0.9, 59 sites: 1.0–1.9, 79 sited: 2.0–4.5 cm). The total detectable incidence of metastases with BS was 66.0 % (105 BM) of all metastases detected in comparison with SPECT/CT (159 BM). Detectability with BS increased with increasing size of detectable foci. Foci less than 1 cm are detected in isolated case (1 from 21 cases). Metastases measuring from 1 cm to 1.9 cm are detected only in 52.5 % of cases (31 from 59 cases). The detectability of large metastases (2 cm or more) with BS (92.4 %) approaches the SPECT/CT (100 %) – 73 from 79 cases. There were detected with BS 27 osteoblastic BM in comparison 56 BM with SPECT/CT (48.2 %). The detectability with BS of mixed BM (76.3 %) and octeolitic BM (75.4 %) showed no differences. Firstly it can be explained by a predominance of smaller osteoblastic foci, and secondly reparative processes in metastases, accompanied by reduction of the radiopharmaceutical. The correction of the conclusion of the BS was required just in 24 cases: in 8 cases, when the BS was marked overdiagnosis, 16 – underdiagnosis. However, BS does not lose its value as a screening. In one case, even if BS has been revealed metastasis, it is not yet accompanied by destruction of bone tissue. Despite such significant differences in diagnostic accuracy of BS and SPECT/CT, BS proved to be uninformative only in 2 cases: when undetected metastases without primary tumor identified, and in the case of the screening of metastasis the accumulation of the radiopharmaceutical in the bladder. In 2 other cases, the lack of accumulation of the radiopharmaceutical was determined by the reparation that can only be considered conditionally uninformative. However, SPECT/CT shows clear advantages in the visualization of bone metastases due to computed tomography, allowing to estimate the structure of bone tissue. In 9 cases even to SPECT-slices metastases were not accompanied by pathological accumulation of the radiopharmaceutical. Conclusion: SPECT/CT is a highly informative method for detecting bone metastases, the use of which allows reducing the time of examination and dose irradiation of patients due to the rejection of additional radiological procedures. In addition, SPECT/CT at the same time allows differential diagnosis of structural and metabolic bone changes, which increases both the accuracy of primary diagnosis and control of treatment.

Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.

ObjectiveOsteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone.DesignSecretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients. Finally, osteomodulin and fibulin-3 sequences were quantified by western blot and immunoassays in serum and culture supernatants.Results175 proteins were identified in NSC osteoblast secretome. Data are available via ProteomeXchange with identifier PXD008494. Compared to NSC osteoblast secretome, 12 proteins were significantly less secreted (Osteomodulin, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 13 proteins were significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1, CSF-1). Similar changes in osteomodulin, IGF2, SERPINE1, fibulin-3 and CHI3L1 mRNA levels were observed. ELISAs assays confirm the decrease by half of osteomodulin protein in SC osteoblasts supernatant compared to NSC and in OA patients serum compared to healthy subjects. Fibulin-3 epitopes Fib3-1, Fib3-2 and Fib3-3 were also increased in SC osteoblasts supernatant compared to NSC.ConclusionsWe highlighted some proteins differentially secreted by the osteoblasts coming from OA subchondral bone sclerosis. These changes contribute to explain some features observed in OA subchondral bone, like the increase of bone remodeling or abnormalities in bone matrix mineralization. Among identified proteins, osteomodulin was found decreased and fibulin-3 increased in serum of OA patients. These findings suggest that osteomodulin and fibulin-3 fragments could be biomarkers to monitor early changes in subchondral bone metabolism in OA.

Blood biochemical parameters of bone metabolism in cows and calves kept in a beef suckler system during the early postpartum period

The early lactation and early neonatal period are characterised by intense changes in bone metabolism. The aim of this study was to evaluate blood biochemical parameters of bone metabolism during early lactation in cows and neonatal calves. The study was carried out on 13 Simmental cows and 13 beef suckler calves in cow-calf operations. Blood samples were obtained at 6 time points: 6, 12 and 48 h and 7, 14 and 30 d postpartum (pp). An increase in the concentration of total calcium (tCa) of cows 14 d pp (P = 0.04), an increase in the concentration of inorganic phosphorus (iP) 12 and 48 h pp (P = 0.001, P = 0.002, respectively), an increase in bone specific alkaline phosphatase (BALP) and parathyroid hormone (PTH) concentration 7 d pp (P = 0.02, P = 0.02, respectively) and a decrease of total alkaline phosphatase (TALP) activity during the first 14 d pp (P < 0.05) indicated that the early puerperium in cows is an intense period of change in bone and mineral metabolism. An increase of iP and magnesium (Mg) concentrations in calves at 48 h pp (P < 0.01, P < 0.01, respectively), a decrease in BALP concentration at 48 h pp (P = 0.01), higher TALP activity at 30 d pp (P = 0.02) and decreased PTH at 7 d pp (P = 0.04), indicated bone formation and growth in calves. Our results in cows indicated increased bone resorption and Ca loss through milk production. In neonatal calves we demonstrated high bone turnover during the period of intensive growth and development. The results contribute to a better understanding of bone metabolism in the early postpartum period of cows and neonatal period of calves, and also towards the elucidation of disorders of bone metabolism after calving.

Changes in bone metabolism after gastric cancer surgery in men: A prospective observational study.

10 Background: Several reports have showed that bone disorders occur after gastric cancer surgery, however there are few studies that compared pre- and postoperative bone mineral density of the same patient. The purpose of this study was to assess changes in bone metabolism after gastric cancer surgery prospectively. Methods: We prospectively enrolled 39 men undergoing gastrectomy for early gastric cancer. We excluded women to avoid the effect of menopause. Patients with severe kidney disease requiring dialysis treatment, patients with severe liver disease and patients with treatment with bisphosphonates or any other bone-active drugs were also excluded. Dual energy X-ray absorptiometry (DEXA) was performed before and 1 and 2 years after surgery to evaluate bone mineral density (BMD). The serum levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), estradiol, and alkaline phosphatase (ALP) were measured before surgery and every three months until two years after surgery. Results: DEXA revealed that BMD was significantly decreased by 0.036±0.033 g/cm2 at 12 months after gastrectomy (P &lt; 0.001). The serum ALP was significantly increased by 38.88±6.42 IU/l at 24 months after surgery (P = 0.013), and there was a marginally significant correlation between the changes in BMD and the changes in the serum ALP at 24 months after surgery; the correlation coefficient was -0.30 (P = 0.090). The serum 25(OH)VD was significantly decreased by 4.88±6.42 ng/ml at 24 months after surgery (P &lt; 0.001), however there was no significant correlation between the changes in BMD and the changes in the serum 25(OH)VD. The serum 1,25(OH)2VD and estradiol were not significantly changed before and after surgery. The factor significantly correlated to the reductions of BMD at 12 months after surgery included preoperative lower body mass index (BMI); the correlation coefficients was 0.37 (P = 0.025). Conclusions: This study showed a significant reduction in the BMD of gastric cancer patients at 12 months after gastrectomy and suggested that low preoperative BMI could be a high risk factor for the bone disorder after gastric cancer surgery.