Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis

BACKGROUND: Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-alpha and TGF-beta1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. OBJECTIVE: In this study, we evaluated the effects of raloxifene (Evista); Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-alpha and TGF-beta1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. METHODS: Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. RESULTS: It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-alpha and TGF-beta1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-beta1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-alpha levels in the patient group before and after treatment, were lower than those in the control group. CONCLUSION: Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.     

Calcium metabolism in post-menopausal women

To investigate some parameters involved in postmenopausal calcium metabolism we have measured FSH, LH, estradiol (E2), parathyroid hormone (PTH) calcitonin (CT), 25-hydroxy-vitamin D3 (25-OH-D3), total calcium (CaT) and ionic calcium (Ca++) serum levels in 20 healthy postmenopausal women and 20 premenopausal women. The results reported show that the decrease of estradiol levels are associated with a significant decrease in 25-OH-D3 serum levels, possibly as result of a lower concentration of vitamin D binding protein, which is extremely sensitive to changes in oestrogen levels. The PTH levels were similar in both groups studied, which might be explained together with increased ionic calcium levels in postmenopausal women, by decreased parathyroid sensitivity to the blocking action of Ca++.     

老年女性类风湿关节炎合并骨质疏松症的代谢特点分析

目的:探讨老年女性类风湿关节炎(RA)合并骨质疏松症的代谢特点。方法:选择老年绝经后女性RA患者共59例,检测患者血生化代谢指标如血糖、血脂、CRP等和骨代谢指标如骨钙素(OC)、β-胶原特殊序列(β-Crosslaps)甲状旁腺素(iPTH)等,并进行统计分析。结果:骨质疏松患者的绝经时间、病程长度、OC、β-Crosslaps、iPTH显著高于骨量正常和骨量减少的患者,25羟基维生素D显著低于骨量正常和骨量减少的患者(P均0.05)。RA患者的骨密度水平与是否使用激素和X线分期情况无关。结论:老年女性RA患者易发生骨质疏松,出现骨质疏松的RA女性患者绝经时间更长,可出现脂代谢紊乱及明显的维生素D缺乏,并具有高转换型骨代谢特点。     

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation

Objective

The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.

Methods

We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E₂). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E₂. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction).

Results

1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.

Conclusions

The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.     

绝经后骨质疏松症患者血清LECT2水平的临床意义及其预测价值分析

摘要 目的：探讨绝经后骨质疏松症患者血清白细胞衍生趋化因子2（LECT2）水平的临床意义及其预测价值。方法：选择2020年1月～2022年1月湖南师范大学第一附属医院收治的绝经后骨质疏松症患者125例作为研究组,另选取同期体检的绝经后健康女性志愿者120例作为对照组。比较两组血清LECT2水平,并分析血清LECT2水平与腰椎和股骨颈骨密度（BMD）及骨代谢相关指标的相关性;应用受试者工作特征（ROC）曲线分析血清LECT2对绝经后骨质疏松症患者的预测价值。结果：研究组血清LECT2、骨钙素（OC）、I型原胶原N端前肽（PINP）、 I型胶原交联C末端肽（S-CTX）显著高于对照组,腰椎和股骨颈BMD显著低于对照组（P<0.05）。Pearson相关分析显示,绝经后骨质疏松症患者血清LECT2水平与OC、PINP、S-CTX水平呈正相关（P<0.05）,与腰椎和股骨颈BMD呈负相关（P<0.05）。ROC曲线分析显示,血清LECT2、OC、PINP、S-CTX联合检验对绝经后骨质疏松症患者的预测价值的曲线下面积（AUC）为0.856,大于各单一指标预测。结论：绝经后骨质疏松症女性血清LECT2水平升高,其水平与骨代谢指标OC、PINP、S-CTX水平呈正相关,与腰椎BMD和股骨颈BMD呈负相关,血清LECT2联合OC、PINP、S-CTX对绝经后骨质疏松症患者的预测价值较高。     

Effect of estrogen (Premarin) replacement therapy on serum level of total estrogen and urinary excretion of calcium and hydroxyproline in postmenopausal Chinese women

The study subjects included a total of 30 postmenopausal Chinese women, including 14 natural menopausal women, 13 castrated menopausal women and 3 post-irradiated menopausal women. Premarin 1.25 mg/day was given orally for 3 weeks and off one week, repeated for 6 cycles. Fasting morning urine and blood samples were collected before hormone treatment and at the end of 3 weeks, 11 weeks, and 23 weeks of Premarin therapy. Serum total estrogen level was measured by radioimmunoassay. Urinary calcium and creatinine were measured by atomic absorption and Jeffe's reaction, respectively. The concentration of urinary hydroxyproline was determined by Kivirikko's method. After Premarin therapy, the mean concentration of serum total estrogen increased 3 to 4 times from the pretreatment level of 71.7 pg/ml. On the other hand, the mean value of calcium/creatinine (Ca/Cr) molar ratio dropped down from 0.249 to 0.098. The mean value of hydroxyproline/creatinine (HOPr/Cr) molar ratio was reduced from 0.028 to 0.012. In view of the hormonal and biochemical changes after Premarin therapy, it is concluded that estrogen (Premarin) replacement should be effective in the treatment of enhanced bone loss or osteoporosis in postmenopausal women. The relationship of estrogen and calcitonin in the regulation of bone metabolism is also discussed.     

Age-related increase of calcitonin gene-related peptide in rat thyroid and circulation.

Elevated calcitonin levels in thyroid gland extracts and in plasma accompanied by C-cell hyperplasia are frequently found in old rats, in particular those raised in laboratory conditions. In parallel with calcitonin, we demonstrate here that the thyroidal content and plasma levels of immunoreactive calcitonin gene-related peptide (i-CGRP) significantly increase with age in rats (p less than 0.0001). C18 Sep-Pak-extractable i-CGRP level in plasma was 35% of the total i-CGRP. Gel permeation chromatography and rp-HPLC studies revealed a number of immunoreactive molecular forms of CGRP and only 40-50% of the acid-extracted immunoreactivity was coeluted with the synthetic CGRP(1-37). The i-CGRP level measured in plasma was highly correlated with the thyroidal content of CGRP (p less than 0.001) and also with the age of the rat (p less than 0.001), suggesting an age-related increase of contribution of CGRP from thyroid gland into the circulation.     

Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [(13)C]leucine in healthy premenopausal (n = 15, 49 +/- 1 yr) and postmenopausal (n = 18, 53 +/- 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [(13)C]leucine and [(2)H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo (n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.     

Immunoreactive parathyroid hormone and calcitonin in children's cerebrospinal fluid

Cerebrospinal fluid (CSF) levels of immunoreactive parathyroid hormone (iPTH) and immunoreactive calcitonin (iCT) were measured by radioimmunoassay in 23 outpatient leukemic children on maintenance chemotherapy. These hormones were detectable in the CSF of all patients: iPTH 148 +/- 11 pg/ml (mean +/- SEM); iCT 14.3 +/- 0.8 pg/ml. iPTH and iCT were also measured in serum (iPTH 396 +/- 18 pg/ml; iCT 32.3 +/- 1.4 pg/ml). CSF values were significantly lower (p less than 0.001) than serum concentrations; no significant correlation between the two compartments was found. Our study indicates the presence of iPTH and iCT in the CSF of children.     

The effect of osteoporosis on self-report sleep quality in postmenopausal women

We aimed to show the effect of osteoporosis on sleep quality in 59 postmenopausal women. The participants’ bone-mineral density levels were measured by dual-energy X-ray absorptiometry (DEXA). According to their DEXA results, participants were divided into two groups as osteoporotics and controls. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. Fourteen osteoporotic women (43.8%) and four controls (14.8%) were “poor” sleepers (p < 0.05). Postmeno-pausal women with osteoporosis scored greater on the “sleep latency” and “sleep duration” components of PSQI than controls. According to the findings of our study, osteoporosis is a risk factor for poor sleep quality in postmenopausal women.

     

Serum levels of calcitonin, parathyroid hormone and 25-hydroxycholecalciferol in patients with diabetes mellitus

Blood serum levels of calcitonin, parathyroid hormone, calcium, magnesium and inorganic phosphate have been measured in basal condition and following intravenous administration of calcium in 31 patients with diabetes of type I, in 31 patients with diabetes of type II and in 29 healthy subjects. The level of 25-hydroxy cholecalciferol was measured in all these patients in basal condition only. It was found that the basal calcitonin level was significantly higher in patients with both types of diabetes than in healthy subjects. The administration of calcium caused a significantly higher increase in the blood calcitonin level in patients with type I diabetes than in those with type II diabetes. It was found in addition that in women with type II diabetes blood serum level of parathyroid hormone was significantly higher than that in men suffering from diabetes of the same type, suggesting the participation of some sex-related factor in the pathogenesis of the abnormal parathyroid level in these patients.     

Urinary excretion of glycosaminoglycans in patients with postmenopausal osteoporosis.

The organic bone matrix contains glycosaminoglycans (GAG) of which the precise function and importance in bone mineralisation are still unclear. We examined 85 persons--35 healthy women (25 premenopausal [preMP] mean aged 40.7 years; 10 menopausal [MP] mean aged 59.3 years) and 50 patients with postmenopausal osteoporosis [PMOP] at a mean age 60.4 years. The dynamic of urinary excretion of GAG was measured in 24-hour collected urine by precipitation with cetylpyridinum chloride and spectrophotometry at 560 nm, corrected for the level of excretion of creatinine. There was a significant increase in GAG excretion in patients with PMOP compared with healthy persons (8.25 mg/g and 9.53 mg/g vs 24.11 mg/g; p < 0.0001). A significant positive correlation was established between GAG and calcium urinary excretion and a negative one between GAG and serum estradiol levels. During the treatment with calcitonin the excretion of GAG was decreased which can be used for monitoring the changes of bone metabolism.     

绝经后健康妇女甲状旁腺激素基因多态性与骨密度的关系

利用限制性片段长度多态性分析（RFLP）研究北京地区绝经后妇女甲状旁腺激素（PTH）基因多态性与骨密度的关系。筛选健康、无亲缘关系的绝经后妇女185例, 应用双能X射线骨密度仪（DEXA）检测腰椎等部位的骨密度,用PCR-RFLP方法检测绝经后妇女的PTH基因型。绝经后健康妇女中bb、Bb、BB三种基因型的分布频率分别为7.56%、28.11%和64.32%。方差分析显示前臂部位骨密度与PTH基因相关。除华氏三角区外,BB基因型各部位的骨密度值均高于Bb、bb基因型。Logistic回归分析结果显示,bb基因型组骨质疏松与正常妇女存在显著差异（P＜0.001）。 PTH基因中B基因型可能对维持骨量具有一定的作用。     

<Emphasis Type="Italic">CER1</Emphasis>gene variations associated with bone mineral density,bone markers,and early menopause in postmenopausal women

Background

Osteoporosis has a multifactorial pathogenesis characterized by a combination of low bone mass and increased fragility. In our study, we focused on the effects of polymorphisms in CER1 and DKK1 genes, recently reported as important susceptibility genes for osteoporosis, on bone mineral density (BMD) and bone markers in osteoporotic women. Our objective was to evaluate the effect of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene sequence and five selected CER1 SNPs were amplified and resequenced to assess whether there is a correlation between these genes and BMD, early menopause, and bone turnover markers in osteoporotic patients.

Results

Osteoporotic women seem to suffer menopause 2 years earlier than the control group. The entire DKK1 gene sequence analysis revealed six variations. There was no correlation between the six DKK1 variations and osteoporosis, in contrast to the five common CER1 variations that were significantly associated with BMD. Additionally, osteoporotic patients with rs3747532 and rs7022304 CER1 variations had significantly higher serum levels of parathyroid hormone and calcitonin and lower serum levels of osteocalcin and IGF-1.

Conclusions

No significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis and a potential predictive role, combined with bone markers, in postmenopausal osteoporotic women.

     

Production of immunoreactive calcitonin and parathyroid hormone by embryonal carcinoma cells: alteration with retinoic acid-induced differentiation

To determine possible ectopic production of, and altered responsiveness to, specific hormones and growth factors which may be involved in mediating embryonic differentiation and development embryonal carcinoma cells in culture have been employed to serve as an in vitro system of embryogenesis. Exposure of F9 embryonal carcinoma cells to all-trans-retinoic acid previously has been shown to induce differentiation of these undifferentiated stem cells to parietal endoderm and to markedly alter the ability of calcitonin and parathyroid hormone to stimulate adenylate cyclase activity. Evidence is presented that F9 cells secrete immunoreactive calcitonin into the culture medium (200 pg/12 hr/10(7) cells) while parietal yolk sac (PYS) cells secrete immunoreactive parathyroid hormone (800 pg/12 hr/10(7) cells). Retinoic-induced differentiation of F9 cells to endoderm results in a progressive reduction in immunoreactive calcitonin production, while there is an increase in the level of immunoreactive parathyroid hormone found in the conditioned medium. After exposure of F9 cells to retinoic acid for 5 days, little calcitonin is detectable in 12-hr conditioned medium. Changes in the intracellular levels of immunoreactive calcitonin and PTH follow a pattern similar to that noted for changes in the amount of secreted hormones. Thus, immunoreactive calcitonin is produced by undifferentiated F9 cells which possess a calcitonin responsive adenylate cyclase system, while parathyroid hormone is produced by parietal endoderm cells which respond to parathyroid hormone with increased cyclic AMP synthesis. Sephadex G50 gel filtration of F9-conditioned medium shows two peaks of immunoreactive calcitonin with Mr of 3500 and 20,000. Immunoprecipitation of calcitonin from 35S-labeled F9 cells reveals a specific band of 20,000 Mr. Likewise, two peaks of parathyroid hormone immunoreactive material of Mr 8000 and 39,000 are noted after gel filtration of PYS cell-conditioned medium, whereas parathyroid hormone immunoprecipitation from the same cells reveals a specific band of 39,000 Mr. These results raise the possibility that embryo production of these two hormones at specific stages in development may contribute to the regulation of subsequent steps of differentiation.     

绝经后骨质疏松患者血清I型胶原氨基末端、I型胶原羧基末端及骨钙素的表达变化及临床意义

摘要 目的：探讨绝经后骨质疏松患者血清I型胶原氨基末端（NTx）、I型胶原羧基末端（CTX）及骨钙素（BGP）的表达变化及临床意义。方法：选取我院2017年8月-2022年8月收治的60例绝经后骨质疏松患者作为研究对象,将其分为观察组,另选取同期来我院体检的60名绝经后健康志愿者作为对照组。对比两组患者NTx、CTX、BGP表达水平,并建立受试者特征工作（ROC）曲线分析NTx、CTX、BGP对绝经后骨质疏松的诊断效能。3个月后对所有患者进行门诊复查随访,将症状明显明显减轻,X线检查明显改善,骨密度值明显增加的35例绝经后骨质疏松患者分为预后良好组,将其余25例未达到上述标准的患者分为预后不良组,对比两组患者临床一般情况,并应用Logistic回归分析NTx、CTX、BGP对绝经后骨质疏松的预后预测价值。结果：两组受检者NTx、CTX、BGP表达水平对比差异显著,观察组NTx、CTX高于对照组,BGP低于对照组（P＜0.05）; NTx、CTX、BGP三者联合对绝经后骨质疏松的诊断效能优于单一检测（P＜0.05）;预后良好组与预后不良组患者年龄、BMI、合并基础疾病、病程、Ca表达水平对比无明显差异（P＞0.05）,预后良好组与预后不良组患者病情严重程度、骨密度T值、雌二醇、血清NTx、CTX、BGP表达水平对比差异显著（P＜0.05）;logistic回归分析结果表明：CTX、BGP为绝经后骨质疏松的预后不良的独立影响因素（P＜0.05）。结论：绝经后骨质疏松患者血清I型胶原氨基末端、I型胶原羧基末端表达水平高于非骨质疏松群体,骨钙素低于非骨质疏松群体,三者联合可提升绝经后骨质疏松的诊断效能。另外,CTX、BGP作为绝经后骨质疏松的预后不良的独立影响因素,CTX水平越高、BGP水平越低可能预示患者预后不良,因此临床需针对此类患者及时改良治疗措施,提升其预后水平。     

Association of T869C gene polymorphism of transforming growth factor-β1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women

Osteoporosis is the most common metabolic bone disease; it is an important health problem among postmenopausal women. We evaluated the association of three polymorphisms, T869C, C-509T and G915C, of the TGF-β1 gene with bone mineral density (BMD) serum TGF-β1 levels in 278 postmenopausal female osteopenia/osteoporosis subjects and 95 postmenopausal female control subjects. Serum TGF-β1 levels were significantly lower in osteopenia/osteoporosis subjects than in control subjects. Serum TGF-β1 levels of the CT+CC (T869C) genotype group were significantly lower in osteopenia/osteoporosis subjects than in control subjects (11.3 vs 15.8 ng/mL). There was a significant difference in the CT+CC (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (74.18 vs 60.22%; OR = 1.90, 95%CI = 1.16-3.12). In the age group of more than 50 years, subjects with the TC+CC genotype of T869C polymorphism had significantly increased risk of osteopenic/ osteoporotic bones at L1 (OR = 2.36, 95%CI = 1.37-4.07), L2 (OR = 1.71, 95%CI = 1.01-2.90), L3 (OR = 2.21, 95%CI = 1.23-3.98), L4 (OR = 1.74, 95%CI = 1.00-3.03) and the femoral neck (OR = 1.80, 95%CI = 1.04-3.12). The CT+CC genotype of the T869C polymorphism of the TGF-β1 gene was found to be associated with lower serum TGF-β1 in osteopenia/osteoporosis subjects and increased risk of osteopenic and osteoporotic fracture at L1-4, femoral neck and total hip in postmenopausal Thai women. Logistic regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis. We concluded that T869C polymorphism of the TGF-β1 gene has an impact on decreased serum TGF-β1 levels and influences susceptibility to osteopenia/osteoporosis in Thai women.     

Calcitonin, estrogens and the bone

Estrogen deficiency following natural or surgical menopause, is thought to be the main factor leading to postmenopausal bone loss. Furthermore, after estrogen failure a significant reduction of intestinal calcium absorption and a negativization of calcium balance has been observed. The mechanism of estrogen effect on skeletal tissue is not yet fully elucidated. Recently, specific receptors for estrogens in osteoblastic cells have been described; however their low density does not give a full explanation about their functional role. Therefore estrogens act, at least in part, indirectly through calciotropic hormones. In order to further elucidate this issue, we performed some studies in postmenopausal osteoporotic patients and in fertile oophorectomized women. In the first double blind placebo controlled study, after a 1-year estrogen treatment period we observed an increase in bone mineral content in the hormone-treated patients. Furthermore, in all treated patients an improvement of intestinal calcium absorption was detected, while 1,25-dihydroxy-vitamin D serum levels did not show significant changes. To further analyse the relationship between estrogens (E) and calcitonin (CT) in postmenopausal osteoporosis, we performed a double blind placebo controlled study to evaluate the effects of 1-yr estro-progestative treatment on CT secretory reserve, evaluated by calcium infusion test. Blood levels of CT showed a progressive increase during the study period in the hormone-treated group, with a significant increase in the CT response to calcium stimulation test, suggesting a modulation of CT secretion by E. Recently, we performed two studies in fertile oophorectomized women. In the first, we followed longitudinally 24 fertile women for 1 yr. In these patients we measured, before and after oophorectomy, biochemical indexes of bone metabolism and bone mass. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. In the second study, performed on 14 women before and 6 months after oophorectomy, a treatment with conjugated estrogens allowed the correction of the primary intestinal defect responsible for the reduced calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma immunoreactive calcitonin in lung cancer.

We have measured plasma calcitonin in 135 untreated eucalemic men with lung cancer and a control/smoker population. Calcitonin levels were determined by radioimmunoassay and validated by immunoextraction. Plasma immunoreactive calcitonin moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human calcitonin radioimmunoassays of cancer-patient plasmas were detected by parallel plasma incubations in a salmon calcitonin radioimmunoassay system which does not detect human calcitonin and by immunoprecipitation of tracer at the end of radioimmunoassay incubations. Heating fresh plasmas to 65 degrees C for 1.5 hours reduced radioimmunoassay artifacts without loss of calcitonin moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma calcitonin radioimmunoassay measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma calcitonin seemed to be elevated in 18% (14/80) of basal plasma samples obtained from patients with epidermoid or with anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causing no inhibition of antibody-tracer binding in the salmon calcitonin radioimmunoassays, and immunoextractable with human calcitonin antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15/55) of plasmas from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive calcitonin recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated calcitonin is much larger than calcitonin monomer.     

降钙素对骨质疏松大鼠骨密度形态计量学与骨代谢的影响

目的探讨降钙素(密盖息)对骨质疏松大鼠骨密度、骨形态计量学影响以及与血钙、磷、维生素D代谢和生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型(OVX),实验动物分为4个组:模型对照组、密盖息治疗组,盐酸雷洛昔芬治疗组,假手术组。应用HOLOGIC第4代双能X线4500W骨密度仪测定大鼠腰椎、股骨上段骨密度值(BMD);以骨形态计量学测股骨骨小梁面积、矿化沉积率;用ELISA法测定血清IGF-1水平和血清25OHVitD浓度以及血淋巴细胞维生素D受体(VDR)含量。结果密盖息治疗组、盐酸雷洛昔芬治疗组均较OVX组腰椎、股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。密盖息治疗组较盐酸雷洛昔芬治疗组股骨上段骨密度增高,两组之间差异有显著性(P<0.01)。密盖息治疗组骨小梁面积明显增加、矿化沉积率增高。密盖息治疗组、盐酸雷洛昔芬治疗组血清IGF-1浓度值、血清25-OHVitD浓度值升高,与OVX组比较差异有显著性(P<0.01)。各组血淋巴细胞VDR含量无明显变化,与OVX组比较差异无显著性(P>0.05)。结论密盖息能够预防腰椎、股骨上段骨密度丢失,使骨小梁面积明显增加、矿化沉积率增高并且血清IGF-1及血清25-OHVitD浓度值升高,但对VDR含量无明显作用。