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.

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.

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.

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

Patients with chronic kidney disease （CKD） have an extremely poor cardiovascular outcome. Arterial stiff-ness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcifcation in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the defnition of “CKD mineral bone disorder” was created recently, un-derlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We over-view a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyro-phosphates, matrix Gla protein, osteopontin, fbroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcif-cation and we evaluate their connection to impaired ar-terial stiffness in the mirror of recent scientifc results.

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.

Effects of T-2 Toxin Exposure on Bone Metabolism and Bone Development of Mice

T-2 toxin is the most widespread mycotoxin in crops,feed and food,which poses a serious threat to body health.Bone is the main target tissue for T-2 toxin accumulation.Ingestion of food contaminated by T-2 toxin is the main cause of Kashin-Beck disease.However,the specific mechanism of bone damage caused by T-2 toxin is still unclear.In this study,a total of 40 male C57BL/6N mice were divided into four groups and orally treated with 0,0.5,1.0 and 2.0 mg·kg^(-1) body weight T-2 toxin for 28 days.The results showed that exposure to T-2 toxin led to weight loss,bone mineral density reduction and femoral structural damage of mice.In addition,osteoblast-mediated bone formation was inhibited,and osteoclast-mediated bone resorption was enhanced.Meanwhile,the levels of bone metabolism-related hormones including parathyroid hormone,calcitonin and 1,25-dihydroxyvitamin D3 were reduced.More importantly,it was found that the level of neuropeptide Y(a neurohormone)was decreased.These results provided a new perspetive for understanding the osteotoxicity of T-2 toxin.

Bone Morphogenetic Proteins and Bone Metabolism

Bone morphogenetic proteins （BMPs）, a member of transforming growth factor-beta （TGF-beta） superfamily, can induce formation of cartilage and bone and also regulate osteoblasts, osteogenic genes and osteogenesis. BMPs together with hormones and local signals in cellular microenvironment determine differentiation of mesenchymal stem cells. Further researches about BMPs-related genes will provide a new way to un- derstand and treat metabolic bone diseases in humans and animals. This paper introduces bone metabolism-related BMPs and their transcription factors.

EFFECTS OF LEVOTHYROXINE ON BONE METABOLISM IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH). We compared the levels of FT3, FT4, TSH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. Such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

Cistanche Deserticola for Regulation of Bone Metabolism:Therapeutic Potential and Molecular Mechanisms on Postmenopausal Osteoporosis

Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass,destruction of bone microstructure,increased brittleness and therefore fracture.At present,the main treatment of Western medicine is drug therapy such as bisphosphonates,calcitriol,vitamin D,etc.However,long-term use of these drugs may bring some adverse reactions.Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions.Therefore,Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years.Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism.Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis.

Effect of Huangqin Qingre Chubi Capsule on Bone Metabolism and Serum TLR4NF-kB in Rats with Rheumatoid Arthritis

Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.

Effect of Acupoint Catgut-Embedding on the Quality of Life,Reproductive Endocrine and Bone Metabolism of Postmenopausal Women

Objective： To observe the influence of acupoint catgut-embedding therapy on the quality of life （QOL）,the reproductive endocrine and bone metabolism of postmenopausal women.Methods：AA ttoottaall of 65 women with climacteric syndrome were enrolled and randomly assigned to two groups,thirty-three in the treatment group on whom acupoint catgut-embedding was performed with Shenshu （BL23）,Sanyinjiao （SP6） and Guanyuan （CV4） as main acupoints,and thirty-two in the control group who were only medicated with Fufuchun Capsule （妇复春胶囊））..The treatment course for both groups was 3 months.Before and aafftteerr treatment,the clinical symptoms,the QOL score,serum follicle stimulating hormone （FSH）,luteinizing hormone （LH）,eessttrraaddiiooll （（EE 2 ）,testosterone （T）,osteocalcin （BGP）,parathyroid hormone （PTH）,,ccaallcciittoonniinn （CT） aaannnddd alkaline phosphatase （AKP） were measured.In addition,another 28 women with childbearing potential and normal regular menstrual cycle were selected and the reproductive endocrine hormone were tested in the ovulatory period as controls.Results： The levels of serum FSH and LH of postmenopausal women were higher,and serum E 2 and T were lower than those of normal women （P〈00..0011））..After treatment,the levels of serum EE 2 in both groups and T in the treatment group were increased,while in the control group the serum E 2 increase was more significant than that in the treatment group （P〈0.05）,and serum T showed no statistical difference.The levels of serum FSH,LH,BGP,CT,PTH and AKP were reduced significantly in both groups after treatment （P〈00..0055））..The QOL scores were increased remarkably in both groups on physiological functioning,bbooddiillyy pain,general health,vitality,and mental health after treatment （P〈00..0055））,,but the improvement of bodily ppaaiinn and mental health in the treatment group were better than those in the control group （P〈0.01）.There was no significant difference in the therapeutic effect between the two groups after treatment （P〉00..0055））..Conclusions： Acupoint catgut-embedding showed an obvious effect on climacteric syndrome,and enhanced the QOL in postmenopausal women.The therapy could regulate the hypothalamic-pituitary-ovarian axis to raise the serum E 2 level which may be significant in preventing and curing the osteoporosis in postmenopausal women.

Effect of electroacupuncture combined with osteoporosis treatment apparatus on bone metabolism in patients with spinal cord injury

Objective:To observe the effect of electroacupuncture combined with low-frequency pulsed electromagnetic field on bone metabolism in patients with spinal cord injury(SCI).Methods:The 60 SCI patients who met the inclusion criteria were randomly divided into 2 groups by means of a random number table.In the control group,30 patients were treated with osteoporosis treatment apparatus.In the observation group,30 patients were treated with osteoporosis treatment apparatus and electroacupuncture at the foot-shaoyangacupoints [Yánglíngquán(阳陵泉GB 34) and Xuánzhōng(悬钟GB 39) of both sides].The treatment was applied once a day,5 days a week,for 8 weeks.Before and after treatment,the changes of indexes in the two groups,including the bone mineral density(BMD),bone gla-containing protein(BGP),serum alkaline phosphatase(ALP),procollagen type I C-peptide(PICP),and 25-hydroxy-vitamin D [25(OH)D],were observed for comparison.Results:After treatment,in the two groups,the BMD and 25(OH)D indexes of the femoral neck,greater trochanter,and Ward’s triangle region were not significantly changed in comparing with those before treatment(P>0.05),while the BGP,ALP,and PICP indexes were significantly higher than those before treatment(P<0.05).After treatment,in the observation group,the BGP and ALP indexes were significantly increased in comparing with those of the control group,and the difference was statistically significant(P<0.05),whilst the BMD,PICP,and 25(OH)D indexes of the femoral neck,greater trochanter,and wards triangle region,were not significantly different in comparing with the control group(P>0.05).Conclusion:The osteoporosis treatment apparatus can improve bone metabolism in SCI patients,and the curative effect can be enhanced when combined with electroacupuncture at foot-shaoyangacupoints.

Co-regulation of circadian clock genes and microRNAs in bone metabolism

Mammalian bone is constantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and osteoblasts.It is widely recognized that circadian clock genes can regulate bone metabolism.In recent years,the regulation of bone metabolism by non-coding RNAs has become a hotspot of research.MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism,including circadian clock genes.However,research in this field has been conducted only in recent years and the mechanisms involved are not yet well established.Recent studies have focused on how to target circadian clock genes to treat some diseases,such as autoimmune diseases,but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases.Therefore,in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs,aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

Exercise-Dependent Modulation of Bone Metabolism and Bone Endocrine Function:New Findings and Therapeutic Perspectives

Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis

Objective： The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods： Searches of Pub Med and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results： A total of 22 studies with 1492 subjects were included in our research. We identified：（1） a reduction in bone mineral density at lumbar spine（standardized mean difference（SMD）=-0.30, 95% confidence interval（CI） [-0.61,-0.05]）, trochanter（mean difference（MD）=-0.07, 95% CI [-0.10,-0.05]）, femoral neck（MD=-0.05, 95% CI [-0.09,-0.02]）, and total body bone mineral density（MD=-0.33, 95% CI [-0.51,-0.15]）;（2） a reduction in 25-hydroxyvitamin D（MD=-3.37, 95% CI [-5.94,-0.80]） and an increase in serum alkaline phosphatase（SMD=0.71, 95% CI [0.38, 1.05]）;（3） no significant changes in serum parathyroid hormone, calcium, or phosphorus. Conclusions： Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children.

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial

Background Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis.Methods This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis.Results At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3±4.8) % in the raloxifene group and (1.0±4.9) % in the placebo group (P<0.001). There was a mean increase in total hip BMD of (1.4±4.8) % in the raloxifene group and a mean decrease of (0.9±5.0) % in the placebo group (P<0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P>0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P<0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P<0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo. Conclusions Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.