Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis

OBJECTIVE: To assess bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in a cohort of pre- and postmenopausal women with ankylosing spondylitis (AS), and to determine any relationships with markers of bone turnover and disease activity or severity. METHODS: Fifty premenopausal and 16 postmenopausal women with AS were studied. Clinical and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and Bath AS Radiology Index (BASRI). BMD of the hip and spine was measured by DEXA, and QUS measured at the heel. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were assayed. RESULTS: Women with AS (n = 66) had reduced BMD at the hip compared to age and sex matched controls (n = 132). The mean t scores were -1.1 and -2.0, and z scores -0.4 and -0.37, for pre- and postmenopausal women, respectively. Four (6%) had osteoporosis and 34 (52%) had osteopenia according to the WHO definitions. Using a multiple regression model, femoral neck BMD was found to be significantly affected by age, body mass index, and the sacroiliac radiographic score. There were no significant correlations of BMD with disease duration or disease activity. QUS measures did not correlate with DEXA measures of BMD. Women with AS had significantly lower markers of bone formation, OC and BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels. CONCLUSION: Women with AS have reduced hip BMD, 0.39 SD below age and sex matched controls. Bone turnover in women with AS is characterized by low OC and BALP.     

基质金属蛋白酶1、2及其组织抑制因子1与成年女性年龄、骨转换生化指标及骨密度的关系

目的探讨血清基质金属蛋白酶(MMP)-1、MMP-2、组织金属蛋白酶抑制因子(TIMP)-1与女性年龄、骨密度(BMD)及骨转换生化指标之间的关系。方法用ELISA测定591名20～80岁女性的血清MMP-1、MMP-2、TIMP-1、骨碱性磷酸酶(BAP)、骨钙素(OC)和Ⅰ型胶原氨基末端肽(NTX)水平,用双能X线骨密度仪测定多骨骼部位的BMD。结果(1)MMP-1、MMP-2、TIMP-1与年龄呈正相关(均P＜0．01)。(2)按是否绝经分组结果表明：绝经后妇女MMP-2水平较绝经前妇女高[(1272±279)μg/L与(1141±290)μg/L,P＜0．01]。(3)MMP-2与BMD呈负相关(P＜0．05),但多元线性回归分析表明MMP-2不是BMD的预测因子。(4)MMP-2与血清BAP、OC、NTX正相关(均P＜0．01)。(5)绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组、骨量减少组[(1466±313,1222±243,1282±220)μg/L,均P＜0．01]。结论血清MMP-2与骨转换生化指标相关联。血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score −1 to −2.5) and 23 patients (27.7%) had osteoporosis (T < −2.5). The body mass index of patients with normal BMD (T score ≥ −1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

基质金属蛋白酶-1、-2与女性年龄、骨转换生化指标及骨密度的关系

目的 探讨血清基质金属蛋白酶（MMP）-1、MMP-2与女性年龄、骨密度（BMD）及骨转换生化指标之间的关系。方法用ELISA测定591例20-80岁女性志愿者血清MMP-1、MMP-2、血清骨碱性磷酸酶（BAP）、血清骨钙素（OC）和血清Ⅰ型胶原氨基末端肽（NTX）,用DEXA测定腰椎1-4正位总体、股骨颈、Ward三角区、总髋部的BMD。结果（1）MMP-1、MMP-2与年龄呈正相关。（2）绝经后妇女MMP-2水平高于绝经前妇女（P〈0．001）。（3）MMP-2与BMD呈负相关（P〈0．05）,但多元线性回归分析表明MMP-2不是BMD的预测因子。（4）MMP-2与血清BAP、OC、NTX正相关（P〈0．01）。（5）绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组、骨量减少组（P〈0．01）。结论血清MMP-2与骨转换生化指标相关联。血清MMP-2水平升高可能为高骨转换过程（如绝经后骨质疏松症）中的一种伴随表现。     

中老年妇女骨转换生化指标和骨密度的变化

目的 探讨中老年妇女骨转换生化指标与骨密度随绝经的变化.方法 408名符合条件40 ～80岁的女性志愿者,同一时间段留取血清和晨尿,统一用酶免方法 测定血清骨碱性磷酸酶(BAP)、骨钙素和尿I型胶原氨基末端肽(uNTX);用舣能X线骨密度仪测定前后位腰椎1-4(L1-4)、左侧股骨颈的骨密度.结果 (1)BAP、骨钙素和uNTX与年龄、孕次、生育次数和绝经年限呈正相关(均P相似文献   

Bone turnover markers and bone mineral density in children with haemophilia

Summary. During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross‐sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X‐ray absorptiometry and Z‐scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C‐telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm^?2) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL^?1 in the low BMD group (P = 0.012). C‐telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL^?1 in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z‐score.     

Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women

The alphaVbeta3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an alphaVbeta3 integrin antagonist, would potently inhibit bone resorption, thereby increasing bone mass as assessed by bone mineral density (BMD) in women with postmenopausal osteoporosis. In a multicenter, randomized, double-blind, placebo-controlled, 12-month study, 227 women (average 63 yr) with low lumbar spine or femoral neck BMD were randomly assigned to receive 100 or 400 mg L-000845704 once daily (qd), 200 mg L-000845704 twice daily (bid), or placebo. L-000845704 increased lumbar spine BMD (2.1, 3.1, and 3.5% for the 100-mg-qd, 400-mg-qd, and 200-mg-bid treatment groups, respectively, vs. -0.1% for placebo; P < 0.01 all treatments vs. placebo). Only 200 mg L-000845704 bid significantly increased BMD at the hip (1.7 vs. 0.3% for placebo; P < 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P < 0.05). No L-000845704 group increased total body BMD. All doses of L-000845704 resulted in a similar approximately 42% decrease from baseline of N-telopeptide cross-links (P < 0.001 vs. placebo). L-000845704 was generally well tolerated; adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the antiresorptive effect of the alphaVbeta3 integrin antagonist L-000845704 translated into significant increases in lumbar spine BMD. Furthermore, 200 mg L-000845704 bid provided efficacy at the hip sites. These data suggest that the alphaVbeta3 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.     

Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.     

Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women

Objectives To investigate the relationship between serum sclerostin level, body composition, and bone mineral density (BMD) in central south Chinese postmenopausal women. Methods A cross‐sectional study was conducted on 260 healthy central southern Chinese postmenopausal women with vs without osteoporosis, aged 50–76 years old. Dual X‐ray absorptiometry was used to measure the bone mineral content and BMD of the whole body, lumbar spine and left femur, and total body soft tissue composition. Serum sclerostin levels were measured by a quantitative sandwich enzyme‐linked immunosorbent assay. Results Compared with women without osteoporosis, osteoporotic women had a significantly lower level of serum sclerostin (P = 0·001). Serum sclerostin levels were positively correlated with body weight, Ponderal index and fat mass. There was a positive correlation with the BMD of both the whole body and at various sites (P < 0·05), even after controlling for age, age at menopause, height and body weight. Multiple linear stepwise regression analysis showed that serum sclerostin level was the most significant determinant of both whole‐body and lumbar spine BMD, compared with age, age at menopause, fat mass and lean mass. Age had similar impact as serum sclerostin on hip BMD. Conclusions This study showed that in central south Chinese postmenopausal women, serum sclerostin is lower in women with osteoporosis than without. Serum sclerostin is positively correlated with fat mass and BMD for the whole body, lumbar spine and hip.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women

CONTEXT: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival. OBJECTIVE: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. DESIGN AND SETTING: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America. PARTICIPANTS: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. Interventions: SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr). MAIN OUTCOME MEASURES: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety. RESULTS: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups. CONCLUSIONS: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.     

Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole

Purpose

Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported.

Methods

We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship.

Results

Overall, estradiol decreased from 12.6 pg/ml (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD = 0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a significant BMI-independent increase in CTX.

Conclusions

Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12 months of anastrozole treatment, stabilizing thereafter.     

Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men.

Leptin, the product of the ob gene, has been shown to inhibit bone formation in mice. We addressed whether leptin has any role in the regulation of bone mineral density (BMD) in humans. Subjects were 221 adult men with a mean (+/-SD) age and body mass index of 52.1 +/- 8.7 yr and 23.6 +/- 2.8 kg/m2. Serum leptin, carboxyterminal propeptide of type 1 procollagen (PICP; a marker of bone formation), and cross-linked carboxyterminal teleopeptide of type 1 collagen (a marker of bone resorption) were measured by RIA. BMD was assessed by single photon absorptiometry, and total fat mass was determined by bioimpedance analysis. BMD was inversely associated with serum leptin concentrations and total fat mass after adjustment for body weight. PICP, but not cross-linked carboxyterminal teleopeptide of type 1 collagen, was inversely correlated with serum leptin. These results may suggest that an increase in serum leptin reduces bone formation and decreases BMD in adult men. Leptin may be a regulator of BMD in humans.     

胰岛素、胰岛素原对胰岛素抵抗状态下HepG2细胞PAI-1分泌的影响

目的研究胰岛素、胰岛素原对胰岛素抵抗状态下ＨｅｐＧ２细胞ＰＡＩ１分泌的影响。方法选择在合成ＰＡＩ１方面与肝细胞相似的ＨｅｐＧ２细胞，以高浓度胰岛素诱导胰岛素抵抗后，分别用生理浓度的胰岛素、胰岛素原刺激２４小时，以观察胰岛素抵抗状态下ＰＡＩ１活性的变化。结果基础状态下胰岛素抵抗ＨｅｐＧ２细胞与非胰岛素抵抗ＨｅｐＧ２细胞相比，ＰＡＩ１活性差异不明显；胰岛素、胰岛素原刺激后，胰岛素抵抗ＨｅｐＧ２细胞ＰＡＩ１活性明显高于非胰岛素抵抗ＨｅｐＧ２细胞。当培液中同时加入１０－４Ｍ二甲双胍后，胰岛素、胰岛素原介导的ＰＡＩ１过量分泌得到明显抑制。结论在胰岛素抵抗状态下，胰岛素、胰岛素原刺激后ＨｅｐＧ２细胞ＰＡＩ１活性明显增加，而二甲双胍可明显抑制此现象。     

Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer

CONTEXT: Raloxifene is a promising breast cancer prevention agent in postmenopausal women at increased risk for breast cancer. The effects of raloxifene in premenopausal women are unknown. OBJECTIVE: We evaluated the effect of raloxifene in premenopausal women at increased risk for breast cancer on bone mineral density (BMD). DESIGN: This was a phase II clinical trial. SETTING: This study was conducted at an academic medical center. PARTICIPANTS: Thirty-seven premenopausal women at increased risk for breast cancer enrolled in the trial. Thirty subjects began treatment and 27 were evaluable. INTERVENTION: Raloxifene (60 mg daily) and elemental calcium (500 mg daily) were given for 2 yr. Subjects were followed up off medications for 1 yr. MAIN OUTCOME MEASURE: The primary end point was the intrasubject percent change in BMD at 1 yr measured by dual-energy x-ray absorptiometry. RESULTS: The mean baseline lumbar spine density was 1.027 g/cm(2). Lumbar spine density decreased 2.3% at 1 yr (P < 0.00001) and 3.5% at 2 yr (P < .00001). Percent change from yr 2 to 3 was +1.4%. The mean baseline total hip bone density was 0.905 g/cm(2). Total hip density decreased 0.3% at 1 yr and 1.0% at 2 yr (P = 0.033). Percent change from yr 2 to 3 was +1.7%. CONCLUSIONS: Raloxifene use is associated with a decrease in BMD in premenopausal women at increased risk for breast cancer. The clinical significance of this decrease is unknown and is attenuated with stopping raloxifene.     

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine

OBJECTIVE The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN A prospective study over 2 years of postmenopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS Sixty-four postmenopausal women, ages 47 to 74 (61 ±9, mean ± SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n =23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n =23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = ?0.41 P < 0.001, r = ?0.29 P =0.01 and r = ?0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P >0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P =0.0021, 0.034, 0.0017, 0.011 and >0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P <0.05). CONCLUSIONS In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.     

Bone mineral density, collagen type 1 α 1 genotypes and bone turnover in premenopausal women with diabetes mellitus

Summary Osteopenia is a recognised complication of diabetes mellitus which could be due to abnormal bone turnover or disturbances in the calcium/parathyroid hormone/vitamin D axis or both. Genetic factors also play an important part in determining bone mass although this has not been studied in diabetes. Recently a polymorphism of the collagen type 1 α 1 (COL1A1) gene has been shown to be associated with low bone mass in British women. To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20). Bone mineral density was lower at the femoral neck in the subjects with Type I diabetes (p = 0.08) as were serum 25-hydroxyvitamin D compared with control subjects (p = 0.023) and this was negatively correlated with serum collagen type 1 C-terminal propeptide (r = –0.56, p < 0.001). Bone mineral density in Type II diabetes was not different from control subjects, after correction for body mass index. Bone resorption was, however, raised in the Type II diabetic subjects as reflected by the higher urinary deoxypyridinoline values (p = 0.016) and lower collagen type 1 C-terminal propeptide:deoxypyridinoline ratio (p = 0.04). In the whole group studied, subjects with the COL1A1 ’s' genotype had lower bone mineral density at the femoral neck (p = 0.01) which was partly attributable to a lower body mass index. Following multiple regression analysis body mass index and collagen type 1 C-terminal propeptide concentrations remained determinants of bone mass at all three sites, whereas genotype appeared to be a predictor of bone mass at the femoral neck only. We conclude that measurement of these variables could prove useful in firstly identifying those diabetic women at risk of osteoporosis and secondly guiding therapeutic intervention. [Diabetologia (1998) 41: 1314–1320] Received: 2nd March 1998 and in revised form: 27 April 1998