Hormone Replacement Therapy (HRT), Other Reproductive and Life Style Variables and Rheumatoid Arthritis in Postmenopausal Women / 대한류마티스학회지

OBJECTIVE: To compare the differences of hormone replacement therapy (HRT) and reproductive, life style characteristics in postmenopausal women with and without rheumatoid arthritis (RA). METHODS: A total of 360 women, 120 rheumatoid arthritis patients and 240 age matched healthy women were randomly selected from the health care center. Subjects were labeled as rheumatoid arthritis and normal menopausal women. Each group was compared for their HRT status, life style and reproductive characteristics. RESULTS: There were significantly less HRT received subjects in RA group (50.0% vs 76.1%, respectively, OR=0.30, p<0.05). More frequently alcohol consumed in RA group (26.7% vs 11.7%, respectively, p<0.05). There was no significant difference in the history of hysterectomy and smoking as well as body mass index (BMI) between the two groups. Women with serum follicular stimulating hormone (FSH) over 40 IU/L were more frequently observed in RA group (70.0% vs 57.5%, respectively, OR=1.75, p<0.05). CONCLUSION: Increased FSH and history of alcohol drinking were more frequently observed in patients with RA, whereas history of HRT was lower in RA group comparing to that of the control. A prospective study should be designed to confirim the protective effect of HRT and reproductive characteristics on postmenopausal RA patients.

Study on the Insulin Resistance According to Obesity in the Patients with Polycystic Ovarian Syndrome / 대한산부인과학회잡지

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a heterogenous dysfunctional endocrinologic disorder with unknown etiology, clinically characterized by obesity, chronic anovulation, masculinization and infertility. Recently, the association between polycystic ovarian syndrome and insulin resistance have been brought up and insulin resistance is one of the most important factor related to the development of obesity. However, not all polycystic ovarian syndrome patients are obese, it would give a clue to understanding pathophysiology of obesity and PCOS if insulin resistance could be classified according to the degree of obesity in PCOS. Thus, we performed this prospective study to know the relationship between insulin resistance and obesity in the patients with PCOS. METHODS: Fourty eight polycystic ovary patients were included at Samsung Cheil Hospital from April to October 2002. These patients were grouped according to obeseness. HOMA index was used to evaluate insulin resistance calculated by using fasting blood sugar and serum insulin level. RESULTS: Twenty patients (41%) were classified as obese group, twenty eight patients (59%) had normal body mass index. Increased insulin resistance was observed in the patients with polycystic ovarian syndrome. And it was significantly higher in the obese patients compared to the patients with normal body mass index (6.8+/-2.8 vs. 2.7+/-0.9, t-test, p<0.01). CONCLUSION: For increased insulin resistance, immediate management would be needed in the patients of polycystic ovarian syndrome, especially combined with obesity.

Relationship between estrogen receptor thymine-adenine repeat polymorphism and effects of hormone replacement therapy on serum lipid and bone density in postmenopausal women / 대한내과학회지

BACKGROUND: Several biologically plausible mechanisms have been proposed for estrogen-associated changes in lipid and bone metabolism. These effects are thought to be mediated via estrogen receptor (ER). Several polymorphisms in the gene encoding estrogen receptor alpha may modify the effects of hormone replacement therapy on lipid and bone density in postmenopausal women. METHODS: We examined 284 postmenopausal women for thymine-adenine (TA) repeat polymorphism at the ER gene locus and its relationship to lipid and bone density. Their mean age was 52.2+/-5.0 years. We also investigated the association between ER TA repeat polymorphism and changes in lipid and bone density after 3 months and 1 year of hormone replacement therapy. RESULTS: According to the mean number of TA repeats, the women were divided into two groups: group H, with higher number of repeats (TA>16)(n=110); group L, with lower number of repeats (TA

Prevalence of Thyroid Nodules detected by Ultrasonography in Womens Attending Health Check-Ups / 대한내분비학회지

BACKGROUND: Thyroid nodules are commonly found in clinical practice, and the recent development of thyroid ultrasonography has allowed for the detection of small nodules previously undetectable by routine palpations. Since previous studies on thyroid ultrasonography have been focused on patients with known thyroid disorders, we aimed to determine the prevalence of thyroid nodules in a female population. METHODS: We studied women in the age range 30 to 70 years visiting the health promotion center at Samsung Cheil Hospital for routine health check-ups. After excluding patients with previous thyroid disorders, 1300 women where selected to undergo thyroid ultrasonography for the detection of the presence of thyroid nodules. If nodules were found, their size and numbers were recorded, and these data correlated with the patients age. RESULTS: Of the 1300 subjects, thyroid nodules were detected in 490 (37.7%) with their prevalence (p=0.009), and that of multinodularity of thyroid nodules (p=0.001), increasing with the increasing age of the patients (Age 30 to 39: 30.8%, 40 to 49: 37.0%, 50 to 59: 41.5% and 60 to 69: 65.2%). Among these study subjects, nodules larger than 15 mm in size were detected in 29 and after performing fine needle aspirations on 18 nodules, 17 were found to be benign, with 1 papillary carcinoma, which required a total thyroidectomy. CONCLUSION: The prevalence of thyroid nodules in our female study population was 37.7%, with their prevalence, and that of multinodularity of thyroid nodules, increasing with increased age.

The Postpartum Recurrence of Graves'Disease and its Contributing Factors / 대한내분비학회지

BACKGROUND: Pregnancy affects the course of Graves' Disease (GD), and patients who initially maintain euthyroid function into their middle trimester with minimum doses of antithyroid drugs become exacerbated after delivery. Even patients who are completely cured, requiring no treatment during pregnancy, can relapse after delivery. In this study, we examined the postpartum changes in the thyroid functions of patients with GD, and attempted to determine the factors contributing to these changes. METHODS: The study subjects were recruited from pregnant women visiting our outpatient clinic for routine prenatal evaluations. 45 women previously diagnosed with GD, who had been treated and cured with hyperthyroidism, and were no longer taking any thyroid medications, were evaluated for 1 year post delivery. RESULTS: Among 45 patients, 20 (44.4%) developed thyroid disorders following delivery. Postpartum thyroiditis (PPT) developed in 8 patients (17.8%), and GD developed in 12 (26.0%). The onset of the PPT disease 3.1 +/- 1.4 months following delivery, which was significantly earlier than the 6.7 +/- 2.7 months required for the post delivery onset of GD (p=0.003). The TBII values, measured during the thyrotoxic state in each womaen, were negative in women with PPT and positive in 71.4% of women with GD (p=0.030). The duration of treatment for hyperthyroidism prior or pregnancy, the number of recurrences, and the time interval without treatment, were not associated with the development of postpartum thyroid disorders. Whereas, the mean number of past pregnancies for women who developed PPT was 3.9 +/- 2.1, and was significantly higher than the 2.2+/- 1.7 for women developing no thyroid dysfunctions (p=0.044). In 13 women their initial onset of GD occurred within one year postpartum, 7 (53.8%) having had a recurrence, which was significantly higher than in women whose disease onset occurred unrelated to delivery (5 of 32 women: 15.6%). CONCLUSION: Women with GD developed postpartum thyroid dysfunctions in 44.4% of cases. Women whose initial disease onset occurred within one year postpartum had higher recurrences of GD, and women who developed PPT had a history of higher gravidity compared to the euthyroid women postpartum. Therefore, if women with GD develop postpartum thyroid dysfunctions, the diagnosis should be made, and a treatment modality planned, following careful considerations of the patients' past obstetric history, changes in clinical manifestations and the TBII values.

A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women

BACKGROUND: Plasma cholesteryl ester transfer protein (CETP) functions to transfer cholesteryl ester from HDL to triglyceride-rich lipoproteins and regulates plasma HDL cholesterol level. A common mutation, the exon 15 A to G substitution at codon 442 (D442G) results in reduced plasma CETP activity and increased plasma HDL cholesterol level. Meanwhile, hormone replacement therapy (HRT) in postmenopausal women increases plasma HDL cholesterol level. METHODS: We investigated the frequency of D442G mutation and its effect on plasma HDL cholesterol level in Korean women. We also examined if the mutation has any effect on an increase in plasma HDL cholesterol level during HRT. RESULTS: Two hundred and twenty eight women aged over 40 years were recruited in this study. Of 228 women, 22 (9.6%) were identified as having the D442G mutation; 21 heterozygotes and 1 homozygote. The subjects with the mutation had higher plasma HDL cholesterol levels than those without the mutation (61.6 +/- 17.3 vs. 55.1 +/- 14.0 mg/dL, p < 0.05). After 12 month HRT, HDL cholesterol increased by 6.4% (3.6 +/- 13.2 mg/dL, p < 0.05) and D442G mutation did not have any significant effect on the change of plasma HDL cholesterol level. CONCLUSION: D442G mutation is common in Korean postmenopausal women and it is associated with increased plasma HDL cholesterol level. HRT for postmenopausal women increased plasma HDL cholesterol level in similar amounts regardless of the presence or absence of D442G mutation.

Changes of BMD & Markers of Bone Turnover after 1-year Treatment with HRT and Fluocalcic in Postmenopausal Korean Women with Decreased BMD

BACKGROUND: Although fluoride has an ability to increase BMD at lumbar spine, it does not result in a reduction in vertebral fractures. After the introduction of monofluorophosphate instead of NaF, there is a revival of the use of fluoride in the treatment of osteoporosis. METHODS: We evaluated 39 subjects out of the 50 who finished a 1-year treatment. Fifty postmenopausal Korean women with decreased bone density were enrolled from Oct. 2000 to Mar. 2001 and stratified 2-groups by treatment regimen. One group was treated with Fluocalcic (Disodium monofluorophosphate; 100 mg and calcium carbonate; 1,250 mg) and HRT, the other group with HRT only at climacteric clinic in Samsung Cheil Hospital & Women's Healthcare Center. Markers of bone turnover, changes of BMD and demographic data were obtained and compared in both groups. RESULTS: Compared with the baseline value, osteocalcin and total alkaline phosphatase, the formation markers of bone turnover were not decreased significantly after 3-month treatment in HRT and fluoride treated group. But, DPYD, the resorption marker, was decreased slightly after the 3-months treatment. Changes of both resorption and formation markers of bone turnover in HRT only treated group were significantly decreased after the treatment. The spinal BMD increased significantly compared to the baseline value in both groups. Changes of spinal BMD after 1-year treatment in HRT and fluoride treated group was increased significantly than HRT only group (15.1 12.6% vs 4.2 3.4%). CONCLUSION: This study shows that changes of spinal BMD after combined treatment with HRT and fluoride were increased significantly than HRT only treatment. Therefore, combined use of Fluoride and HRT was effective to increase spinal BMD in postmenopausal women with decreased spinal BMD.

Changes of bone mineral density after 2-yrs treatment with HRT and alendronate in osteoporotic Korean women

BACKGROUND: Alendronate is one of the anti-resorptive drugs for the treatment of osteoporosis and results in a decrease of bone turnover. HRT is also known to decrease the bone turnover. Combination therapy with HRT and alendronate has made significant increase of BMD in postmenopausal women. But there were no available long-term results about combination therapy of HRT and alendronate on Korean osteoporotic women. METHODS: Eighty postmenopausal women with osteoporosis who visited the Climacteric clinic in Samsung Cheil Hospital & Women's Health Care Center from Apil to July 1999 were subjects. Randomized open labeled case control study was made. We evaluated 37 postmenopausal osteoporotic Korean women who were treated for 2 years after enrollment. Subjects in Group I were treated with HRT only, and group II had HRT with alendronate 10 mg daily. Subjects also were measured BMD at lumbar spine and markers of bone turnover before, one and two year after treatment. RESULTS: Common reasons for dropouts were side effects of HRT such as breast tenderness, irregular vaginal bleeding, economic problems, long distance from clinic etc. BMD in lumbar spine was increased 10.1% in the first year, and 12.0% in the second year in subjects treated with HRT and alendronate. But in HRT only group BMD increased to 6.4% in the first year and 7.8% at second year. Markers of bone turnover were decreased significantly in both groups compared with baseline value, but the percent changes of markers after 1 year and 2 years between the two groups were not significant. CONCLUSION: This study demonstrated that, in postmenopausal Korean women with osteoporosis, 2 years of combination therapy with HRT and alendronate resulted in a significant and sustained increase in spinal BMD than HRT only group.

A case of small cell carcinoma of the rectum manifesting as pathologic femur neck fracture / 대한내과학회지

Small cell carcinoma of the colon and rectum is a rare primary epithelial malignancy at this location. Histologically, this tumor represents a spectrum of neuroendocrine differentiation. The neuroendocrine cancers of the colon manifest a highly aggressive behavior, even more than their adenocarcinoma counterpart of the same stage. Small cell carcinoma in the colon has early metastasis and the prognosis is extremely poor. We report a case of small cell carcinoma of the rectum manifesting as femur neck fracture during sleep.

Identification of a mutation in the human raloxifene response element of the transforming growth factor-3 gene

The human transforming growth factor-3 (TGF-3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass.

Relationship between maternal weight gain and newborn's birthweight in women with normal glucose tolerance and gestational diabetes / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine the independent factors that predict neonatal birthweight and find the relationship between maternal weight gain and neonatal birthweight in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). METHODS: Forty-six women with GDM and one hundred fifty women with NGT were included in the study. All subjects had singleton pregnancies and no medical diseases that may affect the fetal growth and were certain of gestational age by early ultrasonography. Maternal weight at each prenatal visit was recorded and neonatal anthropometic measurement was done within 2 days of birth. RESULTS: The average rate of weight gain (kg/week) in NGT was lowest during the first trimester (0.09 +/-0.10), peaked during the second trimester (0.52+/-0.14), and slowed after 34 gestational weeks (0.46+/-0.26). In women with GDM, the average rate of weight gain was also lowest during the first trimester (0.18+/-0.23), but it was twofold higher compared with women with NGT. There was a significant decrease of the rate of weight gain after 28 gestational weeks in women with GDM. Total weight gain during pregnancy was 3.4 kg less in women with GDM. Neonatal birthweight was correlated with maternal weight gain and the rate of weight gain during 14-27 and 28-33 weeks in NGT. However, birthweight was correlated with maternal weight gain and the rate of weight gain during the first trimester and 14-27 weeks in GDM. CONCLUSION: This result suggests that the women with GDM who have greater weight gain during the first and the second trimester have a increased risk of excessive fetal growth. Thus strict glycemic control during pregnancy is needed especially in these women.

Thyroid Dysfunction after Abortion / 대한내분비학회지

BACKGROUND: Postpartum thyroiditis is an autoimmune thyroid dysfunction that occurs in the first year after a delivery. Although a postpartum thyroid dysfunction after a full-term pregnancy is well described, little is known about its association with an abortion. The purpose of this study was to investigate the clinical and laboratory findings in thyroid dysfunction that develops after abortion and to investigate the differences in the clinical course according to the types of abortion. METHODS: Thirty patients who were proven to have thyroid dysfunction after either spontaneous or an elective abortion were studied. We analyzed their past history, the type of abortion, their clinical features, the laboratory findings and the courses of the disease. RESULTS: Seventeen patients were hypothyroid and 13 were thyrotoxic at the time of the initial thyroid function evaluation. In the thyrotoxic group, the T3 and free T4 were significantly higher but the TSH was lower than in the hypothyroid group. The titers of antimicrosomal and antithyroglobulin antibody were not different between the two groups. In the thyrotoxic group, 3 cases showed normal values, 2 cases were hypothyroid and the remaining 8 cases were persistently thyrotoxic during the 2 months of observation. TSH receptor antibodies were absent in all of the transient thyrotoxic patients, but they were present in 83.3% of the persistent thyrotoxic patients. The clinical manifestations of the thyroid dysfunction were not different according to the type of abortion. CONCLUSION: Reproductive-age women who have an abnormal thyroid function require careful history taking with respect to their history of regarding parturition or abortion in order to evaluate the possibility of a transient thyroid dysfunction after the abortion.

Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells

Information on precise effects of deflazacort on bone cell function, especially osteoclasts, is quite limited. Therefore, the present study was undertaken to test effects of deflazacort on osteoclast-like cell formation in mouse bone marrow cultures and on the regulation of osteoprotegerin (OPG) and its ligand (RANKL) mRNA expressions by RT-PCR in the ST2 marrow stromal cells. TRAP-positive mononuclear cells increased after the treatment of deflazacort at 10(-9) to 10(-7) M alone for 6 days in a dose-dependent manner. Number of TRAP-positive multi-nucleated cells (MNCs) increased significantly with combined treatment of deflazacort at 10(-7) M and 1,25-(OH)2D3 at 10(-9) M compared to that of cultures treated with 1,25-(OH)2D3 alone (p<0.05). Exposure to deflazacort at 10(-7) M in the presence of 1,25-(OH)2D3 at 10(-9) M in the last 3-day culture had greater stimulatory effect on osteoclast-like cell formation than that of the first 3-day culture did. Deflazacort at 10(-10) -10(-6) M downregulated OPG and upregulated RANKL in mRNA levels in a dose-dependent manner. These observations suggest that deflazacort stimulate osteoclast precursor in the absence of 1,25-(OH)2D3 and enhance differentiation of osteoclasts in the presence of 1,25-(OH)2D3. These effects are, in part, thought to be mediated by the regulation of the expression of OPG and RANKL mRNA in marrow stromal cells.

Metabolic Characteristics and Prevalence of Osteoporosis among Women in Tae-An Area

Understanding the metabolic changes in women is one of the important ways to prevent and treat osteoporosis. To reveal the metabolic characteristics of 289 healthy women aged between 35-65 yr in Tae-An, Korea we evaluated the association between bone mass assessed by broadband ultrasound attenuation (BUA) using quantitative ultrasound 2 (QUS2) and various parameters such as age, body mass index, serum levels of alkaline phosphatase, calcium, phosphorus, parathyroid hormone, 25(OH)D, and urinary ratios of calcium/creatinine and deoxypyridinoline (Dpyd)/creatinine. Among the subjects, 3.0% were osteoporotic, and 40.9% were osteopenic. When the subjects were classified according to their years since menopause (YSM) and age, the prevalence of osteoporosis increased along with an increase of YSM and age. Bone turnover markers such as serum alkaline phosphatase and fasting urinary Dpyd/creatinine were significantly higher in the group with low bone mass than in the normal group. In summary, this study shows, by use of biochemical markers of bone turnover and QUS2, the prevalence of osteoporosis in women aged between 35-65 in Tae-An was 3.0% and the risk of low bone mass increased with the bone turnover markers.

Molecular Diagnosis of 21-hydroxylase (CYP21) Gene mutations in Congenital Adrenal Hyperplasia / 대한산부인과학회잡지

OBJECTIVES: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is most often caused by a deficiency in steroid 21-hydroxylase (21-OH), a microsomal enzyme encoded by the CYP21 gene. Although several CAH causing mutations have been identified in the CYP21 gene of patients with 21-OH deficiency, genotyping of the 21-OH locus is quite complex because of the high frequency of gene conversion and the presence of multiple mutations on single CAH alleles. This study was aimed to analyze the complete characterization of the CYP21 gene coding region in a Korean CAH patient and to conform the PCR-based single strand conformation polymorphism (SSCP) and heteroduplex analysis as a diagnostic tool. METHODS: We used a highly sensitive, non-radioactive method allowing PCR-based single strand conformation polymorphism (SSCP) analysis. This method was applied to the characterization of all the exons and intron-exon junctions of the CYP21 gene in one patients affected by the salt wasting form and 4 normal controls. RESULTS: In all samples showing SSCP abnormal band patterns, sequence analysis showed the presence of sequence variants. In particular, one mutation (I172N) which is already known to cause the disease and 3 silent mutations were detected. CONCLUSION: PCR-based single strand conformation polymorphism (SSCP) and heteroduplex analysis should be useful for the clinical application as a diagnostic tool for the detection of 21-hydroxylase gene mutations.

Effects of obesity on bone mineral density in aged Korean women

BACKGROUND: In general, increased body weight may be a risk factor for hypertension, diabetes, hyperlipidemia, and coronary heart disease. It is very difficult to lose weight especially in aged people. Osteoporosis is commonly developed in aged. Many reports revealed that obesity may prevent bone loss. The protective effect of obesity on bone has been ascribed to a high body fat content. Obese aged people can be very confused whether to decide to lose weight or not. METHODS: We evaluated 137 women aged over 60 who visited a health care center of a university hospital in Seoul from Jan. 1999 to Oct. 1999 to determine the effects of obesity on bone mineral density in aged Korean women. We measured anthropometrical characteristics, BMD of lumbar spine, markers of bone turnover, and FSH of the subjects. RESULTS: The results revealed that obese group had a greater BMD at lumbar spine, but the levels of FSH were noted to be lower than the non obese group. But, none of the markers of bone turnover showed significant differences between the two groups. BMI was positively correlated with BMD (r=0.455, P<0.001) by Pearson's correlation matrix. Also, the level of total alkaline phosphatase significantly had negative association with BMD. The level of FSH revealed that it had a negative correlation (r= 0.290, P<0.01) with BMI. CONCLUSION: We concluded that obesity might have a protective effect related with FSH. Prospective studies on endocrinologic association with BMD, bone markers, FSH and estradiol will be needed.

The Regulation of OPG/OCIF mRNA Epression by IL-1beta in Peripheral Blood Mononuclear Cells / 대한내분비학회지

BACKGROUND: Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.

3\Month follow up results after alendronate therapy in postmenopausal osteoporosis

BACKGROUND: Increased bone turnover results in bone loss after menopause. After menopause, the major cause of bone loss is estrogen deficiency. Rate of bone loss seems to increase after menopause and then formation coupled with resorption is also increased. Antiresorptive drugs are known to be helpful in preventing bone loss. Alendronate is one of antiresorptive drugs for the treatment of osteoporosis which results in a decrease in bone turnover. Some papers report about nonresponders to antiresorptive drugs, and screening people early is very important to optimal management. There are no available data of Korean people. Therefore, this study evaluated the effects of alendronate in Korean postmenopausal osteoporosis patients after 3 months of treatment. METHODS: We studied 96 women with postmenopausal osteoporosis (bone mineral density{BMD} T score<2.5) who visited Climacteric Clinic in Samsung Cheil Hospital from Jan. 1999 to Jul. 1999. Subjects were stratified in to 3 groups: Group 1 treated with alendronate (Fosamax ; MSD, Rahway, NJ, USA) 10mg/day and estrogen, Group 2 treated with calcitonin nasal spray 100 IU every other day and estrogen, and Group 3 treated with estrogen alone for 3 months. We measured serum marker of bone formation (osteocalcin [BGP]), and marker of bone resorption (deoxypyridinoline [DPYD]) from urine at baseline and 3 months after treatment. RESULTS: The mean difference in change of markers among the three groups at the end of study that were significant were BGP 25.7 4.8% and DPYD 23.3 2.3%. DPYD known as bone resorption marker showed a significant response in alendronate and estrogen therapy group than estrogen alone group (P<0.05). Also, BGP showed response to estrogen alone, and calcitonin and estrogen group, but its responsiveness was lesser than alendronate therapy. CONCLUSION: Our data showed that using alendronate with estrogen in patients of osteoporosis further prevents bone resorption. Therefore, we conclude that alendronate therapy with estrogen is helpful in managing osteoporosis patients.

The association of the percentage change of bone mineral density and bone markers after one year of hormone replacement therapy in postmenopausal women

BACKGROUND: To predict the therapeutic efficacy of osteoporosis, one or two years is needed to evaluate the therapeutic effect by the measurement of bone mineral density(BMD), whereas three to six months is sufficient with bone markers. Using this information, we can change therapeutic plan or modulate drug dosage if necessary. This approach would provide appropriate therapy for osteoporosis. The purpose of this study is to evaluate the association between the percentage change of BMD which was measured by peripheral quantitative computed tomography(pQCT), and bone markers after 1 year of hormone replacement therapy(HRT) in healthy postmenopausal women. METHODS: Bone mineral density of nondominant distal forearm in 89 postmenopausal women was measured by pQCT. We measured serum alkaline phosphatase(ALP) and intact osteocalcin(iOC, Novocalcin) as bone formation markers, urinary deoxypyridinoline(dPyr, PyriLinks-D(TM)) as bone resorption marker by using enzyme immunoassay. After 1 year of HRT, 54 subjects dropped out and 33 subjects were reevaluated. RESULTS: After 1 year of HRT, the drop-out rate was 61%. There was no significant difference in age, age of menopause, years since menopause, initial BMD, initial bone markers between remained and drop out groups. But osteocalcin level was significantly high in remained group(p=0.02). ALP(-27.6 %), iOC(-29.9%), dPyr(-25.2%) were significantly decreased after 1 year of HRT(p0.05). The levels of BMD and bone markers between before and after was significantly correlated, demonstrating the homogeneity of response to HRT. The percentage change of trabecular BMD was negatively correhted with the percentage change of dPyr after HRT(r=-0.45, p=0.01). The variance of the percentage change of dPyr contributed to the percentage change of trabecular BMD by 20%. There was no correlation between the percentage change of total BMD or cortical BMD and the change of ALP, iOC, or dPyr after HRT. CONCLUSIONS: After 1 year of HRT in postmenopausal women, all biochemical bone markers were decreased significantly, whereas only trabecular BMD measured by pQCT was increased significantly. This result suggests that bone markers was more sensitive than BMD to monitor the therapeutic efficacy of HRT. The percentage change of trabecular BMD was correlated with the change of dPyr after HRT only. dPyr might be the most sensitive marker among bone markers tested. Therefore, we can predict the change of BMD after HRT through monitoring the levels of dPyr.

A Case of the McCune: Albright Syndrome Associated with Activating Mutations of Stimulatory G Protein / 대한내분비학회지

McCune-Albright syndrome (MAS) is a sporadic disease classically including polyostotic fibrous dysplasia, cafe -au-lait spots, sexual precocity, and other hyperfunctional endocrinopathies. Recent investigations suggest an etiological role for activating embryonic somatic missense mutations in the gene for the a subunit of Gs (Gsa), the G protein that stimulates adenylyl cyclase. DNA from bone, ovary, and blood was analyzed by using polymerase chain reaction and sequenced. A embryological somatic mutation of Gsa gene encoding substitution of a Cys for Arg at amino acid 201 from cells of dysplastic bone and ovary was observed, and the distribution of mutant gene reveals mosaic pattern. We report a case of McCune-Albright syndrome with an activating mutation at codon 201 of Gsa subunit on ovary and bone tissue that was experienced recently.