Bone Metabolic Markers in Patients with Obstructive Sleep Apnea Syndrome

Background： Obstructive sleep apnea syndrome （OSAS） is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers. Methods： A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density （BMD） and the serum levels of total procollagen type 1 N-tenninal propeptide （t-P I NP）, N-terminal midfragment ofosteocalcin （N-MID）, [3-C-terminal telopeptide of type 1 collagen （β-CTX）, vitamin D （VD）, and parathyroid hormone （PTH） were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses. Results： No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels oft-P1NP and [3-CTX in the severe OSAS group were significantly higher than those in the obesity group （48.42 ±23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P 〈 0.001 ; 0.53 ± 0.24 ng/ml vs. 0.41 ±0.13 ng/ml, P 0.011, respectively）. The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups （both P 〈 0.001 ）, and decreased as the severity of OSAS increased （P 〈 0.001）. The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups （both P 〈 0.001 ）. The results of correlation analysis indicated that the level of apnea-hypopnea index （AHI） was correlated with the levels oft-P1NP （r = 0.396, P 〈 0.001 ）, VD （r = 0.404, P 〈 0.001 ）, and PTH （r = 0.400, P 〈 0.001 ）, whereas the level of minimum 02 saturation （SaO2min） was correlated with the levels ofVD （r = 0.258, P=0.016） andPTH（r= 0.376, P〈0.001）. Conclusions： The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.

Correlations of single photon emission computed tomography joints scan and bone metabolic markers in active rheumatoid arthritis

Objective To explore the correlation between quantitative value of joint bone scan by single photon emission computed tomography(SPECT)and serum bone metabolic markers in patients with active rheumatoid arthritis(RA).Methods Clinical data of 60 newly diagnosed RA patients were retrospectively collected in Department

Jianpi Qingchang Bushen decoction improves inflammatory response and metabolic bone disorder in inflammatory bowel disease-induced bone loss

BACKGROUND Bone loss and osteoporosis are commonly described as extra-intestinal manifestations of inflammatory bowel disease(IBD).Jianpi Qingchang Bushen decoction(JQBD)is a prescription used in clinical practice.However,further studies are needed to determine whether JQBD regulates the receptor activator of nuclear factor kappa B(NF-κB)(RANK)/receptor activator of NF-κB ligand(RANKL)/osteoprotegerin(OPG)pathways and could play a role in treating IBD-induced bone loss.AIM To evaluate the therapeutic effect of JQBD in IBD-induced bone loss and explore the underlying mechanisms.METHODS An IBD-induced bone loss model was constructed by feeding 126-to-8-wk-old interleukin-10(IL-10)-knockout mice with piroxicam for 10 d.The mice were randomly divided into model and JQBD groups.We used wild-type mice as a control.The JQBD group was administered the JQBD suspension for 2 wk by gavage,while the control and model groups were given normal saline at the corresponding time points.All mice were killed after the intervention.The effect of JQBD on body weight,disease activity index(DAI),and colon length was analyzed.Histopathological examination,colon ultrastructure observation,and micro-computed tomographic scanning of the lumbar vertebrae were performed.The gene expression of NF-κB,tumor necrosis factor-α(TNF-α),IL-1β,IL-6,and IL-8 in the colon was evaluated by real-time polymerase chain reaction.Colon samples were assessed by Western blot for the expression of RANKL,OPG,RANK,and NF-κB proteins.RESULTS The model group lost body weight,had a shorter colon,and showed a dramatic increase in DAI score,whereas JQBD had protective and therapeutic effects.Treatment with JQBD significantly improved inflammatory cell infiltration and reduced crypt abscess and ulcer formation.Threedimensional imaging of the vertebral centrum in the model group revealed a lower bone mass,loose trabeculae,and“rod-shaped”changes in the structure compared to the control group and JQBD groups.The bone volume/total volume ratio and bone mineral density were significantly lower in the model group than in the control group.JQBD intervention downregulated the NF-κB,TNF-α,IL-1β,IL-6,and IL-8 m RNA expression levels.The RANKL and OPG protein levels were also improved.CONCLUSION JQBD reduces inflammation of the colonic mucosa and inhibits activation of the RANK/RANKL/OPG signaling pathway,thereby reducing osteoclast activation and bone resorption and improving bone metabolism.

Study on Prevention and Treatment of Diabetes in Middle and Aged Women with Kidney Deficiency and Bone Metabolic Disturbance

Objective: To study the therapeutic effect of Chinese herbal medicine (CHM) for supplementing Qi, activating blood circulation and tonifying Kidney on prevention and treatment of diabetes in middle and aged women with Kidney Deficiency and bone metabolic disturbance. Methods: Clinical observation was taken in 52 patients, who were divided into two groups, the control group (treated with hypoglycemic agent alone) and the treated group (treated with hypoglycemic agent and CHM). Results: Before treatment, patients in both groups showed obviously higher blood alkaline phosphatase, β2-microglobulin (β2-MG) level, urinary β2-MG, calcium and phosphorus level, but lower serum estradiol level than those in normal subjects. After 3 months' treatment, no apparent change in serum estradiol level was observed, but other parameters were all lowered obviously in the two groups, with the changes revealed more obviously in the treated group. The symptoms of Kidney Deficiency, such as lumbodorsal pain, fatigue, palpitation and vertigo, were improved after treatment, which was also more obviously in the treated group. Conclusion: CHM for supplementing Qi, activating blood circulation and tonifying Kidney was effective in improving Kidney Deficiency and mineral substance loss in bones in middle and aged diabetic women patients. The CHM and western drugs acted synergistically.

Effects of alendronate on bone mass and organ pathology in ovariectomized mice

Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sham),ovariectomized group(OVX)and ovariectomized+alendronate group(ALN).The sodium alendronate was injected subcutaneously at 400μg/kg twice a week in the ALN group.The equal volume of normal saline was injected subcutaneously twice a week in the SHAM group and OVX group.After 12 weeks of drug administration,the samples were taken.The organ coefficients,main organ pathological sections,and bone histopathological sections were observed,and the micro CT,L4 biomechanics and serum biochemical indicators were analyzed.Results:The uterine coefficient of Sham group was(0.0054±0.0007)significantly higher than that of OVX group(0.0026±0.0009)and ALN group(0.0025±0.0007),and the difference was statistically significant(P<0.05).No obvious lesions or toxic or side effects were observed in the main organs.Compared with the OVX group,the ALN group with decalcified sections of bone tissue had compact trabecular structure and fewer adipocytes.Micro-CT results showed that the Tb.BMD,Tb.N,Tb.Th and Tb.BV/TV values of the ALN group were significantly increased compared with those of the OVX group,but the Tb.Sp value was significantly decreased,and the difference was statistically significant(P<0.05).In L4 vertebral body biomechanics,the elastic modulus(50.29±13.43)and maximum load number(29.83±4.92)of ALN group were significantly higher than those of OVX group(14.77±3.12)and maximum load number(11.57±3.18),and the difference was statistically significant(P<0.05).Compared with the OVX group,the serum OCN and PINP indicators of bone formation in the ALN group were increased,while the bone resorption indicators TRACP-5b and CTX-I were decreased,with statistical significance(P<0.05).Conclusion:Alendronate sodium improves bone quality by increasing bone density,improving bone microstructure,increasing bone strength,promoting bone formation and inhibiting bone resorption,without obvious toxic and side effects on organs.

From liver to hormones:The endocrine consequences of cirrhosis

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

Effects of different doses of metformin on bone mineral density and bone metabolism in elderly male patients with type 2 diabetes mellitus

BACKGROUND Diabetes is a chronic disease,which may cause various complications.Patients with diabetes are at high risk of bone and joint disorders,such as osteoporosis and bone fractures.In addition,it became widely accepted that diabetes has an important impact on bone metabolism.Metformin is a commonly used and effective first-line treatment for type 2 diabetes.Some glucose-lowering agents have been found to have an effect on bone metabolism.The present study explored if different doses of metformin have an effect on bone mineral density(BMD)and bone metabolism in type 2 diabetes.AIM To investigate the effects of different doses of metformin on BMD and bone metabolism in elderly male patients with type 2 diabetes mellitus.METHODS A total of 120 elderly male outpatients with type 2 diabetes mellitus who were admitted to our hospital were included in the study from July 2018 to June 2019.They were randomly assigned to an experimental group and a control group with 60 patients in each group.Patients in the experimental group were given high dose metformin four times a day 0.5 g each time for 12 wk.Patients in the control group were given low dose metformin orally twice a day 0.5 g each time for 12 wk.The changes in bone mineral density and bone metabolism before and after treatment and the efficacy rate of the treatment were compared between the two groups.RESULTS There was no significant difference in the efficacy rate between the two groups(P>0.05).Before the treatment,there was no significant difference in BMD and bone metabolism between the two groups(P>0.05).However,after the treatment,BMD and bone metabolism were improved in the two groups.Moreover,BMD and 25-hydroxyvitamin D were significantly higher in the experimental group than in the control group,and N-terminal/midregion andβ-isomerized Cterminal telopeptides were significantly lower in the experimental group than in the control group(all P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION Both high and low dose metformin can effectively control the blood glucose levels in elderly male patients with type 2 diabetes mellitus.However,the benefits of high dose metformin in improving BMD and bone metabolism level was more obvious in patients with type 2 diabetes mellitus.

Causes and treatment of idiopathic benign paroxysmal positional vertigo based on endocrinological and other metabolic factors

The genesis of the Benign Paroxysmal Positional Vertigo(BPPV)seems to be related to some metabolic factors.These factors,such as vitamin D,glucocorticoids,and even thyroid and growth hormones,can affect bone metabolism and the mineralization of otoconia.It also seems to link to factors related to aging or nutritional habits.Besides,since the incidence of BPPV is quantitatively higher in women than in men,female sex steroids could be associated with this process.It could be useful to understand how these factors act in otoconial mineralization if we want to develop treatments aimed at preventing or delaying BPPV recurrences.In this review,we will analyze the role of these metabolic and hormonal factors in otoconial mineralization and in the treatment of BPPV.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Reduced Bone Mineral Density and Bone Metabolism in Aquaporin-1 Knockout Mice

An overt phenotype of aquaporin-1 knockout（AQP1 ko） mice is growth retardation, suggesting possible defects in bone development and metabolism. In the present study, we analyzed the bone mineral density（ BMD）, bone calcium and phosphorus contents, and bone metabolism in an AQP1 ko mouse model. The BMD of femurs in AQP1 ko mice was significantly lower than that of litter-matched wildtype mice as measured by dual energy X-ray absorptiometry. Consistently, the contents of bone total calcium and phosphorus were also significantly lower in AQP1 ko mice. The reduced BMD caused by AQP1 deficiency mainly affect male mice. Bone metabolic activity, as indicated by 99m^Tc-MDP absorption measurements, was remarkably reduced in AQP1 ko mice. These results provide the first evidence that AQP1 play an important role in bone structure and metabolism.

Effect of Different Calcium Supplements on Bone Metabolism in Rats

Osteoporosis, characterized by loss of bone mass and microarchitectural deterioration of bone tissue, results in enhanced bone fragility and increases risk of fractureIll. In China, the incidence of primary osteoporosis is as high as 50%-70% in 60-69 years old females and approximately 30% in 60-69 years old males[21, which is closely related with the low intake of calcium. According to the nationwide nutrition and health survey in 2002 in China, the average daily calcium intake of Chinese residents is 391 mg, accounting for 41% of the recommended calcium intake.

Effect of Zinc on Bone Metabolism in Fetal Mouse Limb Culture

Objective To determine the effects of zine-deficiency and zine-excess on hone metabolism. Methods We developed the culture model of fetal mouse limbs (16th day) cultivated in self-made rotator with continuing flow of mixed gas for six days in vitro. The cultured limbs were examined by the techniques of 45Ca tracer and X-roentgenography. Results The right limbs cultivated had longer bone length, higher bone density than the left limbs uncultivated from the same embryo; and histologically, the right limbs had active bone cell differentiation, proliferation, increased bone trabecula. clearly calcified cartilage matrix, and osteogenic tissue. Compared with the control group, the zinc-deficient group and zine-excess (Zn2+ l20) μmol/L) group contained less osteocalcin (BGP) and 45Ca content, and lower AKP activity; whereas zine-normal (Zn2+ 45 μmol/L and Zn2+ 70 μmol/L) groups contained more BGP and 45Ca contents, and higher AKP (alkaline phosphatase) activity. Conclusion Both zine-deficiency and zine-excess can alter bone growth and normal metabolism. The results indicate that the culture model of fetal mouse limbs (16th day) in vitro can be used as a research model of bone growth and development.

Animal Modelling of Lumbar Corpectomy and Fusion and in vivo Growth of Spine Supporting Bone by Titanium Cage Implants: An Experimental Study

In this study a lumbar spinal fusion animal model is established to assess the effect of spinal fusion cage,and explore theminimum area ratio of titanium cage section to vertebral section that ensures bone healing and biomechanical property.Lumbarcorpectomy was conducted by posterolateral approach with titanium cage implantation combined with plate fixation.Titaniumcages with the same length but different diameters were used.After implantation of titanium cages,the progress of bone healingwas observed and the bone biomechanical properties were measured,including deformation and displacement in axial compression,flexion,extension,and lateral bending motion.The factors affecting the in vivo growth of spine supporting body wereanalyzed.The results show that the area ratio of titanium cage section to vertebral section should reach 1/2 to ensure the bonehealing,sufficient bone intensity and biomechanical properties.Some bone healing indicators,such as BMP,suggest that there isa relationship between the peak time and the peak value of bone formation and metabolism markers and the bone healing strength.

Adipose tissue in bone regeneration-stem cell source and beyond

Adipose tissue(AT)is recognized as a complex organ involved in major homeostatic body functions,such as food intake,energy balance,immunomodulation,development and growth,and functioning of the reproductive organs.The role of AT in tissue and organ homeostasis,repair and regeneration is increasingly recognized.Different AT compartments(white AT,brown AT and bone marrow AT)and their interrelation with bone metabolism will be presented.AT-derived stem cell populations-adipose-derived mesenchymal stem cells and pluripotentlike stem cells.Multilineage differentiating stress-enduring and dedifferentiated fat cells can be obtained in relatively high quantities compared to other sources.Their role in different strategies of bone and fracture healing tissue engineering and cell therapy will be described.The current use of AT-or AT-derived stem cell populations for fracture healing and bone regenerative strategies will be presented,as well as major challenges in furthering bone regenerative strategies to clinical settings.

Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Regulation of bone metabolism mediated byβ-adrenergic receptor and its clinical application

Recent studies have confirmed thatβ-adrenergic receptors(β-ARs)are expressed on the surface of osteoblasts and osteoclasts,and that the sympathetic nervous system can regulate bone metabolism by activating them.β-AR blockers(BBs)are commonly used in the treatment of cardiovascular diseases in the elderly.It is important to investigate whether BBs have a beneficial effect on bone metabolism in the treatment of cardiovascular diseases,so as to expand their clinical application.This article reviews the effects of BB on bone metabolism and the progress of clinical research.

Effects of Different Hemodialysis Treatments on Abnormal Mineral and Bone Metabolism in Patients with Chronic Renal Failure

Objective:To investigate the effects of different hemodialysis treatments on abnormal mineral and bone metabolism in patients with chronic renal failure.Methods:A random number table was used to divide 80 patients with chronic renal failure admitted to our hospital from January 2018 to January 2019 into 2 groups,with 40 cases in each group.Group A was treated with low-flux hemodialysis,and group B was treated with high-flux hemodialysis.The related indicators of mineral and bone metabolism of the two groups were compared.Results:Before treatment,the blood calcium,blood phosphorus,intact parathyroid hormone(iPTH),type I procollagen amino terminal peptide(PINP),fibroblast growth factor 23(FGF23),serum creatinine(Scr)indicators of the two groups were compared.The difference was not statistically significant(P>0.05);After treatment,the blood calcium levels of the two groups were higher than before treatment,the blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than before treatment,and the blood calcium level of group B was higher than that of group A,while blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than group A,the difference was statistically significant(P<0.05).Conclusion:Compared with low-flux hemodialysis,patients with chronic renal failure treated with highflux hemodialysis have better results,which can correct abnormal bone metabolism and improve Scr levels.

Effect of Pioglitazone on Transdifferentiation of Preosteoblasts from Rat Bone Mesenchymal Stem Cells into Adipocytes

We aimed to examine the effect of pioglitazone on transdifferentiation of preosteoblasts from rat bone marrow mesenchymal stem cells(BMSCs) into adipocytes and investigate its effect on bone metabolism.BMSCs were harvested from the femurs and tibias of a rat,then separated,purified,proliferated for 3 generations and differentiated into preosteoblasts for 5 days and 14 days respectively in the presence of osteogenic medium.Thereafter,the preosteoblasts were cultured for 21 days in the presence of adipogenic medium with and without pioglitazone(1 μg/mL).Partially-differentiated osteoblasts were identified by mineralized nodules with Alizarin red S staining.Transdifferentiated adipocytes were identified by Oil Red O staining.Reverse transcription PCR(RT-PCR) was performed to assay the expression levels of osteogenic markers Runx2 and ALP,and an adipogenic marker PPARγ.Those cells cultured for 5 days did not show mineralized nodules as detected by staining of Alizarin red S,while those cultured for 14 days showed dispersed mineralized centers in the form of brown spots,although without obvious red mineralized nodules.After adipogenic transdifferentiation for 21 days,adipose-drops were found in cells of 5CG and 5EG earlier than those of 14CG and 14EG,and the former showed much more adipocytes separately as detected by Oil Red O staining.Whatever the time was 5 days or 14 days of BMSCs osteogenic differentiation,the cells cultured with pioglitazone showed much more adipocytes than those without pioglitazone.Our experiment showed that the less time it took for BMSCs osteogenic differentiation,a stronger ability remained for BMSCs to transdifferentiate into adipocytes.The mRNA expression levels of Runx2 and ALP were decreased by 1.79 and 1.90 times respectively in 5EG(P< 0.05) as compared with 5CG,and that of PPARγ was increased by 1.31 times in 5EG(P<0.05) as compared with 5CG.The mRNA expression levels of Runx2 and ALP were decreased by 1.45 and 1.54 times respectively in 14EG(P<0.05) as compared with 14CG,and that of PPARγ was increased by 1.39 times in 14EG(P<0.05) as compared with 14CG.It was concluded that pioglitazone stimulated the transdifferentiation of BMSCs into adipocytes.These observations provided a potential mechanism of imbalance in thiazolidinedione induced bone metabolism.

Postprandial response of bone turnover markers in patients with Crohn's disease

AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.