Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.

Regulation of bone phosphorus retention and bone development possibly by related hormones and local bone-derived regulators in broiler chicks

Background:Phosphorus is essential for bone mineralization in broilers,however,the underlying mechanisms remain unclear.We aimed to investigate whether bone phosphorus retention and bone development might be regulated by related hormones and local bone-derived regulators in broilers.Methods:Broilers were fed diets containing different levels of non-phytate phosphorus(NPP)0.15%,0.25%,0.35%,0.45% and 0.55% or 0.15%,0.22%,0.29%,0.36% and 0.43% from 1 to 21 or 22 to 42 days of age.Serum and tibia samples were collected for determinations of bone phosphorus retention and bone development parameters,related hormones and local bone-derived regulators of broiler chickens on d 14,28 and 42,respectively.Results:Tibia ash phosphorus,total phosphorus accumulation in tibia ash(TP_(TA)),bone mineral concentration(BMC),bone mineral density(BMD),bone breaking strength(BBS),and ash on d 14,28 or 42,serum 1,25-dihydroxyvitamin D_(3)(1,25(OH)_(2)D_(3))on d 28 and 42,mRNA expressions of tibia fibroblast growth factor 23(FGF23)and dentin matrix protein 1(DMP1)on d 14 and 28 increased linearly or quadratically(P<0.05),while serum parathyroid hormone(PTH)on d 28,tibia alkaline phosphatase(ALP)on d 14,28 and 42,bone gal protein(BGP)on d 14,and mRNA expression of tibia phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX)on d 14 and 28 decreased linearly or quadratically(P<0.04)as dietary NPP level increased.TPTA,BMC,BMD,and ash on d 28 and 42,BBS on d 28,and ash phosphorus on d 42 were positively correlated(r=0.389 to 0.486,P<0.03)with serum 1,25(OH)_(2)D_(3).All of the above parameters were positively correlated(r=0.380 to 0.689,P<0.05)with tibia DMP1 mRNA expression on d 14,28 and 42,but negatively correlated(r=−0.609 to−0.538,P<0.02)with serum PTH on d 28,tibia ALP on d 14,28 and 42,and BGP on d 14.TP_(TA),BMC and ash on d 14 and BMD on d 28 were negatively correlated(r=−0.397 to−0.362,P<0.03)with tibia PHEX mRNA expression,and BMD on d 28 was positively correlated(r=0.384,P=0.04)with tibia FGF23 mRNA expression.Conclusions:These results suggested that bone phosphorus retention and bone development parameters had moderate to strong correlations with serum PTH and 1,25(OH)2D3 and tibia DMP1,PHEX,FGF23,ALP and BGP in broilers during the whole growth period,and thus they might be partly regulated by these related hormones and local bone-derived regulators.

Bone flare after initiation of novel hormonal therapy in patients with metastatic hormone-sensitive prostate cancer:A case report

BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.

ASSOCIATION OF PARATHYROID HORMONE GENE POLYMORPHISM WITH BONE MINERAL DENSITY IN CHINESE WOMEN

Objective.To investigate the distribution frequency of parathyroid hormone(PTH)gene polymorphism in healthy adults from Bejing area and to explore the association of PTH genotypes with bone mineral density(BMD).Methods.PTH gene polymorphism was detected in270subjects by polymerase chain reaction(PCR)and PCR /restriction fragment length polymorphism(PCR /RFLP).The digestion products of restriction enzyme Bst B1were separated on1%agarose gels.PTH genotypes were confirmed by DNA sequences analysis.BMD was measured by dual-energy X-ray absorptiometry(DEXA,DPX -L ,Lunar).Results.Genotype frequencies of BB,Bb,bb were73.7%,25.9%and0.4%respectively in Beijing adults(P<0.01),67.1%,32.2%and0.7%in postmenopausal women,which was different from Japanese wom-en.We statistically compared bone mineral density at the lumbar2-4and proximal femur between BB and Bb genotypes.No obvious association was found between the BMD and PTH genotypes in Beijing women(P>0.05).Conclusion.PTH gene polymorphism is not associated with BMD in Chinese women.The further research to explore the genetic risk factors of osteoporosis should be committed.

Correlation of sex hormones with adipocytokines and bone metabolism biochemical indexes in women with menopausal osteoporosis

Objective:To investigate the correlation of sex hormones with adipocytokines and bone metabolism biochemical indexes in women with menopausal osteoporosis.Methods: A total of 118 female patients who were diagnosed with menopausal osteoporosis in the West China Second University Hospital of Sichuan University between September 2015 and October 2017 were selected as menopausal osteoporosis group, and 100 menopausal women with normal bone density who received medical examination in the West China Second University Hospital of Sichuan University during the same period were selected as normal control group. The contents of sex hormones, adipocytokines and bone metabolism biochemical indexes in peripheral blood were compared between two groups of women, and Pearson test was used to evaluate the correlation between sex hormones and disease severity in women with menopausal osteoporosis.Results: E2 content in the peripheral blood of menopausal osteoporosis group was significantly lower than that of control group whereas FSH and LH contents were not significantly different from those of control group;Resistin and chemerin contents in peripheral blood were higher than those of control group whereas LEP and Visfatin contents were lower than those of control group;OC, NBAP, TRACP and ICTP contents in peripheral blood were significantly higher than those of control group. Pearson test showed that the sex hormone E2 content in women with menopausal osteoporosis was directly correlated with the contents of adipocytokines and bone metabolism biochemical indexes.Conclusion: The sex hormone expression is abnormal in women with menopausal osteoporosis, and the specific abnormal level can objectively reflect the condition of osteoporosis.

United observation and analysis of the effect of tripterygium wilfordii on sex hormone levels, apoptosis in ovary and bone metabolism in female rats

Objective:To study the effect of tripterygium wilfordii on sex hormone levels, apoptosis in ovary and bone metabolism in female rats.Methods: Adult female SD rats were chosen as experimental animals and divided into model group and control group, model group were made into premature ovarian failure models through intragastric administration of tripterygium wilfordii, and control group were given intragastric administration of same dose of normal saline. Serum was collected 14 d after model making to determine the contents of sex hormones and bone metabolism markers, ovarian tissue was collected to determine the expression of apoptosis genes and tibial tissue was collected to determine the expression of bone metabolism marker genes.Results: FSH, LH,β-CTX and TRACP5b levels in serum of model group were significantly higher than those of control group whereas E2, PINP and N-MID levels were significantly lower than those of control group;Fas, FasL, APAF-1 and Caspase-3 mRNA expression in ovarian tissue of model group were significantly higher than those of control group whereas Bcl-2 and XIAP mRNA expression were significantly lower than those of control group;RUNX2, BAP and OPG mRNA expression in bone tissue of model group were significantly lower than those of control group whereas RANKL and RANK mRNA expression were significantly higher than those of control group.Conclusion:There are sex hormone changes, apoptosis aggravation in ovarian tissue and systemic bone metabolism disorder in rat model with tripterygium wilfordii-induced premature ovarian failure.

Comparison between recombinant human parathyroid hormone(1-34) and elcatonin in treatment of primary osteoporosis

Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

The importance of the thyroid hormone axis in the regulation of skeletal growth and maintenance has been well established from clinical studies involving patients with mutations in proteins that regulate synthesis and/or actions of thyroid hormone. Data from genetic mouse models involving disruption and overexpression of components of the thyroid hormone axis also provide direct support for a key role for thyroid hormone in the regulation of bone metabolism. Thyroid hormone regulates proliferation and/or differentiated actions of multiple cell types in bone including chondrocytes, osteoblasts and osteoclasts. Thyroid hormone effects on the target cells are mediated via ligand-inducible nuclear receptors/transcription factors, thyroid hormone receptor （TR） a and ~, of which TRa seems to be critically important in regulating bone cell functions. In terms of mechanisms for thyroid hormone action, studies suggest that thyroid hormone regulates a number of key growth factor signaling pathways including insulin-like growth factor-I, parathyroid hormone related protein, fibroblast growth factor, Indian hedgehog and Wnt to influence skeletal growth. In this review we describe findings from various genetic mouse models and clinical mutations of thyroid hormone signaling related mutations in humans that pertain to the role and mechanism of action of thyroid hormone in the regulation of skeletal growth and maintenance.

Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports

Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.

Osteoblast-restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes

Growth hormone （GH） exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 （IGF-1） in liver and skeletal tissues. To examine the requirement for the GH receptor （GHR） in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-l-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts （△GHR）, which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female AGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female AGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a ＂feminization＂ of bone geometry in 16 week-old mice, as observed by faCT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male AGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater extent than previously appreciated in establishing the sexual dimorphism of the skeleton.

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency

BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.

Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

AIM： To investigate the association between serum insulin-like growth factor 1 （IGF-1）, osteocalcin, and parathyroid hormone （PTH） levels with the etiology and clinical condition of patients with chronic liver disease. METHODS： Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection： bilharziasis （9 patients）, hepatitis B virus （HBV, 12 patients） and hepatitis C virus （HCV, 29 patients）. The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group.HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction （RT-PCR）. Antibllharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted. RESULTS： Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin （14.7 ± 0.54 vs 3.6 ± 0.10, P 〈 0.05）, while that for PTH was positively correlated with total protein （70.1 ± 2.17 vs 6.7 ± 0.10, P 〈 0.05） in patients with HCV infection.

Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.

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.

阿仑磷酸钠辅助PVP治疗对老年骨质疏松性压缩性骨折BALP、PTH及N-MID-OT水平的影响

目的分析阿仑磷酸钠辅助经皮椎体成形术(PVP)治疗对老年骨质疏松性压缩性骨折骨碱性磷酸酶(BALP)、甲状旁腺激素(PTH)及N端中段骨钙素(N-MID-OT)水平的影响。方法选取2019年1月至2022年2月唐山市丰润区人民医院收治的老年骨质疏松性压缩性骨折患者107例,按照治疗方式不同分为观察组和对照组,对照组采取PVP治疗(n=52),观察组采取阿仑磷酸钠辅助PVP治疗(n=55)。对比两组Oswestry功能障碍指数问卷表(ODI)、视觉模拟量表(VAS)、骨代谢指标(BALP、PTH、N-MID-OT水平)、不良反应及再骨折发生率。结果两组术后2个月、6个月、12个月ODI评分均下降,且观察组术后各时间段ODI评分均低于对照组,差异有统计学意义(P<0.05)。两组术后2个月、6个月、12个月VAS评分均下降,且观察组术后各时间段VAS评分均低于对照组,差异有统计学意义(P<0.05)。两组术后BALP、PTH及N-MID-OT水平均下降,且观察组术后BALP、PTH及N-MID-OT水平均低于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率对比,差异无统计学意义(P>0.05),但观察组再骨折发生率(7.28%)明显低于对照组(25.00%),差异有统计学意义(P<0.05)。结论阿仑磷酸钠辅助PVP治疗可有效改善老年骨质疏松性压缩性骨折患者椎体功能,减轻其疼痛程度,改善患者体内BALP、PTH及N-MID-OT水平,促进其术后恢复。

个体化绝经激素治疗对围绝经期妇女骨密度改善的疗效分析

目的观察绝经激素治疗(MHT)对绝经综合征患者围绝经期症状的改善效果和对骨密度(BMD)的影响,分析MHT对围绝经期患者的综合收益。方法选取2018年7月至2022年7月就诊于宁夏医科大学总医院生殖内分泌门诊BMD减低的绝经综合征患者232例,按谈话后是否自愿接受MHT将其分为研究组(MHT组,n=106)和对照组(非MHT组,n=126)。对照组仅口服钙剂和维生素D,研究组在口服钙剂和维生素D基础上添加雌孕激素。于治疗前、治疗后采用改良Kupperman评分表评估患者围绝经期症状,并测定腰椎1~4及股骨颈的BMD。结果最终完成试验共218例,其中研究组100例、对照组118例,脱失率6.03%(14/232)。治疗前两组患者间改良Kupperman评分及各检测部位的BMD比较均无显著差异(P>0.05)。研究组治疗后6个月和治疗后1年改良Kupperman评分较治疗前显著减低(P<0.05),且均达正常值;对照组患者治疗后Kupperman评分均较治疗前略有降低,但均无显著性差异(P>0.05)。研究组治疗后BMD均较治疗前升高,治疗后1年BMD较治疗前显著升高(P<0.05);对照组治疗后BMD均较治疗前有所升高,但均无显著性差异(P>0.05)。结论绝经激素治疗在绝经综合征患者中的应用可明显改善围绝经期症状,同时可增加腰椎及股骨颈的骨密度,从而改善和预防骨质疏松,大大提高围绝经期妇女的生活质量,增加其临床获益。

Clinical manifestations of low bone mass in amenorrhea patients with elevated follicular stimulating hormone

OBJECTIVE: To study the characteristics of low bone mass in amenorrhea patients with elevated follicular stimulating hormone (FSH). METHODS: Amenorrhea patients with elevated FSH: Primary amenorrhea 18 cases, secondary amenorrhea 171 cases and age matched controls with normal menstruation, 180 cases. The descriptive parameters were: estrogen, alkaline phosphatase, urinary excretion of calcium to creatine ratio, cortical bone mineral density at the right radius measured by single photon absorptiometry and trabecular bone mineral density at the lumbar vertebra body measured by quantitative computerized tomography. RESULTS: Average E(2) levels in amenorrhea patients is under 150 pmol/L with significantly higher alkaline phosphatase and urine calcium to creatine ratio values than the normal menstruation group. Cortical bone mineral density in the secondary amenorrhea group (655 +/- 69 mg/cm(2)) was significantly lower than that of the normal menstruation group (677 +/- 56 mg/cm(2), P

矮小症儿童骨密度与25羟维生素D相关性分析

目的:探讨矮小症儿童的骨密度,分析骨密度与25羟维生素D的相关性。方法:将88例矮小症儿童列为观察组,与88例身高正常儿童的骨密度比较;分析观察组骨密度与25羟维生素D的相关性。根据是否生长激素缺乏、是否青春发育、维生素D营养状态将观察组进行分类,比较各类状态的骨密度。结果:观察组儿童的骨密度Z值低于对照组(P=0.004)。矮小症儿童基线骨密度Z值与25羟维生素D无相关性(r=0.007,P=0.947)。生长激素缺乏症组的骨密度Z值低于特发性矮身材组,但差异无统计学意义(P=0.321)。青春期组儿童的骨密度Z值低于青春期前组,差异有统计学意义(P=0.001)。维生素D不足组的矮小儿童骨密度与年龄、骨龄呈负相关(r=-0.579、-0.573,P<0.001),与25羟维生素D无相关性(P=0.436)。结论:矮小症儿童骨密度Z值低于身高正常儿童,青春发育者尤明显;25羟维生素D值不能反映矮小症儿童的骨密度水平,骨量积累不足需考虑时间累积效应。

益气续骨方调节PI3K/Akt信号通路对激素性股骨头坏死大鼠骨代谢的影响

目的探究益气续骨方调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路对激素性股骨头坏死大鼠骨代谢的影响。方法将50只SD雄性大鼠随机分为正常组、模型组、益气续骨方低剂量组、益气续骨方高剂量组、益气续骨方+LY294002组,每组10只。除正常组外,其余组大鼠右臀肌肉注射醋酸泼尼松龙注射液4周建立激素性股骨头坏死模型。造模结束后,益气续骨方低、高剂量组大鼠分别给予益气续骨方0.5 mL(含生药0.285 g/mL)和1 mL(含生药0.57 g/mL)灌胃,益气续骨方+LY294002组大鼠给予益气续骨方1 mL灌胃并腹腔注射6 mg/kg的LY294002,正常组和模型组给予等体积生理盐水灌胃,均1次/d,连续干预8周。ELISA检测大鼠血清白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血钙、血磷、骨保护素(OPG)、骨钙素(OCN)、碱性磷酸酶(ALP)水平,Micro-CT检测观察股骨头形态,HE染色观察股骨头组织病理形态,TRAP染色观察破骨细胞生成情况,Western blot法检测股骨头组织中骨特异性转录因子2(Runx2)、骨形态发生蛋白2(BMP-2)、裂解半胱天冬酶-3(Cleaved-Caspase-3)、PI3K、Akt蛋白表达情况。结果与正常组比较,模型组大鼠血清IL-4、IL-6、TNF-α、OPG、ALP水平和骨小梁分离度(Tb.Sp)、空骨陷窝率及股骨头组织中Cleaved-Caspase-3蛋白相对表达量均明显升高(P均<0.05),血钙、血磷、OCN水平和骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)及股骨头组织中Runx2、BMP-2、p-PI3K/PI3K、p-Akt/Akt蛋白相对表达量均明显降低(P均<0.05),破骨细胞数量增多,股骨头破坏、骨小梁空间结构紊乱;与模型组比较,益气续骨方低、高剂量组大鼠血清IL-4、IL-6、TNF-α、OPG、ALP水平和Tb.Sp、空骨陷窝率及股骨头组织中Cleaved-Caspase-3蛋白相对表达量均明显降低(P均<0.05),血钙、血磷、OCN水平和BV/TV、Tb.N、Tb.Th及股骨头组织中Runx2、BMP-2、p-PI3K/PI3K、p-Akt/Akt蛋白相对表达量均明显升高(P均<0.05),破骨细胞数量减少,股骨头破坏程度减轻,骨小梁空间结构形态改善;LY294002可减弱益气续骨方对上述指标的改善作用,各指标与益气续骨方高剂量组比较差异均有统计学意义(P均<0.05)。结论益气续骨方可改善激素性股骨头坏死大鼠骨代谢,降低炎症因子水平,减少破骨细胞数量,减轻大鼠股骨头坏死,机制可能与激活PI3K/Akt信号通路有关。

基于PI3K/Akt/mTOR信号通路、性激素、骨代谢探究知柏地黄丸联合治疗女性特发性性早熟的效果及机制

目的探讨联合知柏地黄丸对女性特发性性早熟(CPP)患儿性激素、骨代谢及PI3K/Akt/mTOR信号通路的影响。方法选取2022年1月—2022年12月收治的60例CPP患儿,随机数字表法分为西药组、联合组2组,均30例。西药组给予注射用曲普瑞林治疗,联合组在西药组基础上联合知柏地黄丸治疗。比较2组临床疗效、安全性,以及治疗前后子宫体积、卵巢体积、卵泡直径、性激素水平[促黄体生成素(LH)、LH/促卵泡激素(FSH)、雌二醇(E_(2))]、骨代谢指标[骨钙素、骨碱性磷酸酶(BALP)、Ⅰ型前胶原氨基端肽(PⅠNP)、骨密度、β-胶原降解产物(β-CTX)]、PI3K/Akt/mTOR信号通路相关蛋白表达。结果联合组总有效率96.67%(29/30)高于西药组70.00%(21/30)(P<0.05)。联合组治疗后子宫体积、卵巢体积、卵泡直径均低于西药组(P<0.05);联合组治疗后血清LH、LH/FSH、E_(2)、骨钙素、BALP、PⅠNP水平低于西药组,骨密度高于西药组(P<0.05)。2组治疗后血清β-CTX水平比较无显著差异(P>0.05)。联合组治疗后PI3K、Akt、mTOR蛋白表达水平低于西药组(P<0.05)。联合组不良反应总发生率与西药组比较无显著差异(P>0.05)。结论注射用曲普瑞林联合知柏地黄丸能降低CPP患儿性激素水平,改善骨代谢相关因子的表达,抑制PI3K/Akt/mTOR信号通路活性,从而改善患儿症状。研究结果表明该方案临床疗效确切,且具有一定安全性。