Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis

BACKGROUND: Biochemical markers of bone turnover can provide prognostic information about the risk of fracture and may be useful for monitoring efficacy of antiresorptive and anabolic therapy in osteoporosis. We evaluated the performance of a fully automated assay for serum total N-terminal propeptide of type I collagen (P1NP), a marker of bone formation. METHODS: Serum P1NP was measured on the Elecsys 2010 automated analyzer (Roche) in 230 healthy premenopausal women, age 30-49 years, 179 postmenopausal women with osteoporosis participating in the previously published 1 year randomized Parathyroid Hormone and Alendronate for Osteoporosis study of full-length parathyroid hormone (PTH 1-84, >100 microg/day subcutaneously; n = 119) or oral alendronate 10 mg/day (n = 60), and 64 healthy men, age 40 to 65 years. RESULTS: The within-run and between-run (total) imprecision (CVs) were < or =1.7% (n = 20) and 4.4% (n = 15), respectively. The median within-person variability of results (3 measurements over 3 months in 15 postmenopausal women) was 7.2%, resulting in a least significant change (LSC) value of 20%. Serum P1NP concentrations were 74% (P <0.0001) higher in postmenopausal women than in premenopausal controls. After 3 months of treatment, 83% and 88% of patients treated with PTH 1-84 and alendronate, respectively, demonstrated changes of serum P1NP that exceeded the LSC. CONCLUSION: The automated assay for serum total P1NP is precise and sensitive enough to detect changes that exceed the LSC in a majority of postmenopausal women after 3 months of treatment with PTH 1-84 or alendronate. Because of its convenience and high throughput, this bone formation marker may be useful for the monitoring of patients with osteoporosis.     

Markers of bone resorption--measurement in serum, plasma or urine?

OBJECTIVE: We compared an established urine marker (total deoxypyridinoline (DPD), related to creatinine (cr)) with a plasma marker (CTX) to evaluate whether the methods are equally suited to detect increased bone resorption in women after the menopause and to see whether both markers show normal bone resorption in postmenopausal women on hormone replacement therapy (HRT). METHODS: DPD in first morning void urines was measured by an automated HPLC system. CTX ("beta-CrossLaps") was measured on the automated electrochemiluminescence analyzer E170 (Roche Diagnostics, Germany). For CTX, EDTA plasma and serum samples taken from fasting patients in the morning between 08.00 and 08.30 were analyzed. 49 women were premenopausal, 43 women were postmenopausal without HRT, and 13 women were postmenopausal on HRT (mostly on oral medication) for more than six months. RESULTS AND DISCUSSION: Inter-assay coefficients of variation (CVs) at three different concentrations were 6.0%, 6.7% and 7.2% for the assay of DPD and 2.58%, 1.83% and 1.99% for CTX, respectively. CTX was more stable in EDTA plasma than in serum. 21/43 (49%) of postmenopausal women without HRT showed increased DPD/cr ratios and 19/43 (44%) showed elevated CTX concentrations. Regarding postmenopausal women on HRT, DPD/cr ratios were elevated in 3/13 women, whereas plasma CTX showed levels within the premenopausal range in all 13 women. It is discussed that in some cases a lower muscle mass as a result of increasing age or as a result of oral HRT might increase the urinary DPD/cr ratio by lowered excretion of cr. This effect would raise the number of cases with an elevated DPD/cr ratio after the menopause out of proportion. CONCLUSION: CTX is determined with very high precision on the E170. CTX, if measured in EDTA plasma samples from fasting patients in the morning, seems to indicate bone resorption in women on HRT correctly as normal. The DPD/cr ratio in urine of women on HRT is increased in some cases above normal, presumably by lowered excretion of cr. According to our results, plasma (or serum) markers of bone resorption seem to be preferable over cr-related urine markers.     

Different acute responses of serum type I collagen telopeptides, CTX, NTX and ICTP, after repeated ingestion of calcium

BACKGROUND: N- and C-terminal fragments of type I collagen such as NTX, CTX and ICTP are released into circulation during bone resorption and can be quantified in serum. Their respective sensitivity as indices of osteoclastic activity was compared after a short-term inhibition of resorption induced by repeated drinking of calcium-fortified water. METHODS: Serum NTX, CTX and ICTP were measured by specific immunoassays in one group of 15 subjects sampled at 08.00, 11.00, 14.00 and 17.00 (referred to as T0, T3h, T6h and T9h) and having ingested in two experimental periods 660 ml of either low-calcium mineral water or the same low-calcium mineral water fortified with calcium (300 mg/l) at three times (08.00, 11.00 and 14.00). RESULTS: Oral intake of calcium-fortified water resulted in progressive decrease in serum CTX (by 38.7% at T3h, 61.0% at T6h and 60.4% at T9h) and NTX (by 19.0% at T3h, 24.1% at T6h and 25.2% at T9h) while serum ICTP concentrations were not significantly affected. Since ingestion of low-calcium water induced a modest but significant decrease in both CTX (-19.4%) and NTX (-10.6%) we compared the two sets of assays with repeated-measures two-factor analysis of variance with interaction. Ingestion of calcium-fortified water vs. low-calcium water resulted in a significant decrease in both serum CTX (time, P<0.0001; treatment, P<0.0001; time-by treatment, P<0.0001) and NTX (time, P<0.0001; treatment, P=0.0001; time-by treatment, P=0.0066). CONCLUSIONS: CTX is more sensitive than NTX while ICTP is not sensitive to calcium-induced acute changes in osteoclastic activity. The present results stress the importance of choosing appropriate biochemical bone markers to demonstrate the effects of calcium on bone resorption.     

The relationship among history of falls,osteoporosis, and fractures in postmenopausal women

OBJECTIVE: To study the relative contribution of osteoporosis and falls to the occurrence of symptomatic fractures in postmenopausal women. DESIGN: Retrospective survey of current osteoporosis in relation to falls and fractures in the preceding year. SETTING: Patients of general practitioners of the area around a Belgian university. PARTICIPANTS: A total of 2649 consecutive postmenopausal women (mean age, 61y; range, 45-91y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Current bone density measurements (single-photon absorptiometry in the forearm) were analyzed in relation to self-reported incidence of falls and fractures in the preceding year. RESULTS: Osteoporosis was found in 15% of the patients, 19% reported 1 or more falls during the preceding year, and 1.8% had a fracture during the preceding year. The age-adjusted risk for a fracture in the past 12 months for a 1 standard deviation decrease in bone density was 1.9 (95% confidence interval [CI], 1.4-2.5; P<.01). Adjusted risk for age, bone density, and body mass index (BMI) for a fracture in the past 12 months in patients who reported a fall was 6.0 (95% CI, 3.1-11.5; P<.001). Compared with women without osteoporosis and without a fall, women with osteoporosis without a fall had an age- and BMI-adjusted fracture risk of 2.8 (95% CI, 0.6-12.8; P<.10), and women with osteoporosis and a fall had an adjusted-fracture risk of 24.8 (95% CI, 6.9-88.6; P<.0001). CONCLUSIONS: Falls are a major contributing factor to the occurrence of symptomatic fractures in postmenopausal women, independent of and additive to the risk attributable to age and osteoporosis.     

Broadband ultrasound attenuation in the os calcis: relationship to bone mineral at other skeletal sites

1. We have examined the relationship between broadband ultrasound attenuation in the os calcis and measurements of bone mineral in the distal forearm and lumbar spine of normal and postmenopausal osteoporotic women. 2. Values of broadband ultrasound attenuation in postmenopausal women with vertebral osteoporotic fractures were significantly lower (35%) than in normal pre- and peri-menopausal women (55.4 +/- 3.8 and 79.6 +/- 0.8 dB/MHz, respectively). 3. Broadband ultrasound attenuation correlated significantly with bone mineral content measured in the distal forearm by single-photon absorptiometry (r = 0.77, P less than 0.0001) and with bone mineral content (r = 0.66, P less than 0.0001) and bone mineral density (r = 0.72, P less than 0.0001) measured in the lumbar spine by dual-photon absorptiometry. 4. Although significant, these correlations are not sufficiently close to be predictive. However, the accuracy of broadband ultrasound attenuation in discriminating between normal subjects and patients with vertebral fracture compared very favourably with direct measurements in the spine by dual-photon absorptiometry. 5. Broadband ultrasound attenuation, but not the other measurements, correlated significantly with age in the osteoporotic patients (r = 0.50, P less than 0.05). 6. These findings may reflect the partial dependence of broadband ultrasound attenuation on the intrinsic trabecular architecture of cancellous bone, the disruption of which contributes to an increase in fracture risk.     

绝经前与绝经后妇女血清硬化素水平的变化及其相关影响因素

目的:探究绝经前与绝经后妇女血清硬化素水平的变化及其相关影响因素。方法:纳入符合条件的绝经前和绝经后妇女各30例,检测其血清硬化素水平、相关血生化指标、性激素水平和骨转换生物标志物。采用双能X线进行股骨颈,腰椎和髋骨骨密度检测。结果:与绝经前比较,绝经后妇女雌二醇(P<0.01)、雌激素(P=0.01)、游离雌激素指数(P=0.01)和各部位骨密度均显著下降;绝经后妇女与绝经前妇女相比血清硬化素水平升高(P=0.02);由于绝经前妇女多口服避孕药,故后续数据分析仅限于绝经后妇女。绝经后妇女血清硬化素水平与游离雌激素指数(r=-0.57,P=0.01),甲状旁腺激素(r=-0.48,P=0.03)及股骨颈骨密度(r=-0.49,P=0.01)呈负相关;多元回归分析发现,游离雌激素指数(β=-0.63,P=0.01)和甲状旁腺激素(β=-0.56,P=0.01)是血清硬化素水平升高的独立危险因素。结论:绝经后妇女血清硬化素水平高于绝经前妇女。血清硬化素水平可能受到雌激素和甲状旁腺激素的调节作用。     

Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for degradation products of type I collagen C-tlopeptides

BACKGROUND: The Elecsys beta-CrossLaps serum assay measures type I collagen degradation fragments (beta-CTx) that contain the beta-isomerized octapeptide EKAHD-beta-GGR. We investigated the analytical performance of the assay and changes in beta-CrossLaps in patients with metabolic bone diseases. METHODS: The electrochemiluminescent sandwich immunoassay uses two monoclonal antibodies directed against different regions of the linear EKAHD-beta-GGR. RESULTS: beta-CrossLaps (beta-CTx) immunoreactivity was stable in serum and plasma stored at 4 degrees C for 24 h or at room temperature for 4 h, and it did not decrease appreciably in samples stored at -30 degrees C for 12 weeks. Nine cycles of repeated freezing-thawing did not affect serum beta-CTx. The intra- and interassay imprecision (CVs) for four samples was < or = 2.6% (n = 10) and < or = 4.1% (n = 10), respectively. The mean day-to-day biological variation (CV) was 20% in 10 postmenopausal women (n = 10 days). Serum beta-CTx and osteocalcin were correlated in patients with hyperparathyroidism (r = 0.796; P <0.0001; n = 28), chronic renal failure on hemodialysis (r = 0.784; P = 0.0003; n = 16), hypoparathyroidism (r = 0.950; P = 0.0001; n = 11), and pseudohypoparathyroidism (r = 0.987; P = 0.130; n = 4). Serum beta-CTx decreased by 47.4% +/- 8.8% (mean +/- SD) and 60.7% +/- 6.5% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy in 34 women. These decreases were greater than the decreases in urinary excretion of deoxypyridinoline (31.8% +/- 3.9% and 38.1% +/- 4.4%, respectively) or pyridinoline cross-linked C-terminal telopeptide of type I collagen (15.9% +/- 3.9% and 16.9% +/- 4.6%, respectively). CONCLUSIONS: The Elecsys beta-CrossLaps serum assay provides a potentially useful tool for assessing bone resorption state, including its response to estrogen replacement therapy.     

老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系

目的 调查老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系.方法 调查576例60～97岁老年男性吸烟等情况,按照是否吸烟分成吸烟组31例和非吸烟组545例.检测两组骨转换标志物[包括I型胶原羧基末端肽交联(CTX)、I型前胶原氨基端前肽(P1NP)和骨钙素(OC)]、骨密度[包括股骨颈骨密度(FNBMD)...     

绝经后骨质疏松症患者血清几丁质酶壳三糖苷酶、血管活性肠肽水平与骨密度及骨代谢标志物的相关性研究

目的　探讨绝经后骨质疏松症（postmenopausal osteoporosis, PMOP） 患者血清几丁质酶壳三糖苷酶1（Chitortiosidase 1, CHIT1）,血管活性肠肽（vasoactive intestinal peptide, VIP）水平与骨密度及骨代谢标志物的相关性。方法　纳入厦门大学附属东南医院2017 年12 月～ 2020 年12 月收治的PMOP 患者60 例为PMOP 组,取同期于医院体检的绝经后妇女60 例为对照组,比较两组血清CHIT1 和VIP 水平、腰椎L1-4 和股骨颈的骨密度、甲状旁腺素（parathyroid hormone, PTH）、I 型羧基端交联端肽胶原（type I collage cross-linked-telopeptide, CTX）和I 型前胶原氨基端前肽（procollagen I N-terminal peptide, PINP）水平,分析上述指标的相关性,观察PMOP 发生的影响因素。结果　PMOP 组血清CHIT1（9.64±2.25）,CTX（0.52±0.13mg/L）,PINP（60.84±23.51 mg/L） 水平高于对照组（5.83±1.26nmol/mol/h,0.25±0.07mg/L, 39.83±12.52mg/L）,血清VIP（161.32±27.86 pg/ml）,PTH（10.49±2.52pmol/L）水平以及腰椎L1-4（0.74±0.13g/cm2）,股骨颈的骨密度（0.62±0.0.14g/cm2）低于对照组（302.61±43.92pg/ml,15.19±4.64pmol/L,1.19±0.16g/cm2,0.88±0.12g/cm2）, 差异均有统计学意义（t=6.110 ～ 21.042,均P=0.000）。PMOP 患者血清CHIT1 水平与血清PTH,腰椎L1-4,股骨颈的骨密度呈负相关（r=-0.327,-0.479,-0.485,均P ＜ 0.05）,与血清CTX,PINP 水平呈正相关（r=0.482,0.423,均P ＜ 0.05）,血清VIP 水平与血清PTH,腰椎L1-4,股骨颈的骨密度呈正相关（r=0.515,0.482,0.535,均P=0.000）,与血清CTX,PINP 水平呈负相关（r= -0.414,-0.386,均P ＜ 0.05）。Logistic 回归分析提示,CHIT1 ＞ 7.73nmol/mol/h 是PMOP 发生的危险因素,而VIP ＞ 231.97pg/ml,腰椎L1-4 骨密度＞ 0.97g/cm? 是预防PMOP 发生的保护性因素（P ＜ 0.05）。结论　PMOP 患者血清CHIT1 水平增高,而VIP 水平降低,且二者均与腰椎L1-4,股骨颈骨密度以及骨代谢标志物有相关性,临床有望将二者作为评估PMOP 病情的辅助指标。     

Measurement of C-terminal telopeptide of type I collagen (CTX) in serum

Serum CTX assays measure a fragment of the C-terminal telopeptide of type 1 collagen released during resorption of mature bone. Assay reagents are available in manual and automated formats and give good analytical performance. However their standardisation is not transparent and significant differences in results between methods have been demonstrated. CTX is most stable in EDTA plasma, although serum samples processed promptly would be satisfactory. sCTX shows a profound circadian rhythm, especially in non-fasting subjects; specimens should be collected from fasting patients at a well-defined time of day to minimise biological variation. Reference intervals in pre-menopausal women have been well studied but in other adult groups there is less information. Healthy children show the expected age-related variation corresponding to growth rate. Serum CTX fulfils or partially fulfils all the criteria of a reference bone turnover marker. Further studies aimed at reducing inter-method differences in results and establishing the relationships of sCTX with fracture risk and with fracture risk improvement with treatment are required.     

Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial

OBJECTIVES: To determine the efficacy of alendronate treatment on risk of vertebral fracture in a subgroup of women from the Fracture Intervention Trial who had bone mineral density T scores between -1.6 and -2.5 at the femoral neck and to describe how soon after initiation of therapy alendronate becomes effective and whether it is consistent in women with and without existing radiographic vertebral fracture. PATIENTS AND METHODS: From May 1992 to March 1997, postmenopausal women aged 55 to 80 years were randomized to receive alendronate at 5 mg/d for 2 years and 10 mg/d thereafter or placebo for up to 4.5 years (mean, 3.8 years) in a controlled, double-blind, multicenter study. RESULTS: A total of 3737 postmenopausal women were included in the study, 1878 in the alendronate group and 1859 in the placebo group. Risk of vertebral fracture was significantly reduced by alendronate compared with placebo for clinical (relative risk [RR], 0.40; 95% confidence interval [CI], 0.19-0.76; P=.005) and radiographic (RR, 0.57; 95% CI, 0.41-0.81; P=-.002) fracture. The reductions in vertebral fracture risk were consistent in women with and without an existing radiographic vertebral fracture for clinical (RR, 0.34; 95% CI, 0.12-0.84; and RR, 0.46; 95% CI, 0.16-1.17; respectively) and radiographic (RR, 0.53; 95% CI, 0.34-0.82; and RR, 0.64; 95% CI, 0.38-1.10; respectively) fractures. In both groups, the effect of alendronate on clinical vertebral fracture was noted soon after therapy was initiated. The absolute risk of vertebral fracture was low in women without a baseline radiographic fracture. CONCLUSIONS: In women with low bone mass who do not meet the bone mineral density criterion for osteoporosis, alendronate is effective in reducing the risk of vertebral fractures. The absolute benefit of this therapy in women with a T score between -1.6 and -2.5 is greater in women with an existing vertebral fracture and/or with other risk factors. The effect of alendronate occurs early.     

Calcitonin load test to assess the efficacy of salmon calcitonin

BACKGROUND: Monitoring treatments of osteoporosis is required to identify patients not responding to the treatment in a way that reflects mechanism of action of the antiresorption drug on bone. Neither bone mineral measurement nor the available biochemical markers of bone remodeling can be used to monitor efficacy of treatment with nasal spray salmon calcitonin (sCT) since the changes in individual patients are modest and do not exceed the least significant change. METHOD: The novel calcitonin load test (CLT) was developed to assess the biological response to sCT in postmenopausal osteoporotic women. The CLT is based on the time course and an extent of suppression of serum C-terminal telopeptide of types I collagen (CTX) after the intranasal and subcutaneous administration of sCT. The CLT was conducted in 30 untreated postmenopausal osteoporotic women (control group, mean age, 67.7+/-8.4 years), and in 120 postmenopausal osteoporotic women (mean age, 68.5+/-8.1 years) treated with 200 IU of sCT (Miacalcic Nasal, Novartis, Switzerland), for up to 8.4 years (mean, 3.5+/-2.1 years). RESULTS: After 90 min from the intranasal administration of 400 IU of sCT, a decrease (p<0.01) in serum CTX by 58+/-11% was found in the control group, and by 60+/-11% in 74% of the treated patients. In the remaining treated patients, the decrease in CTX did not exceed the least significant change. The number of patients not responding to the CLT increased with duration of the treatment up to 34% in patients treated for over 4 years. Of the non-responders to the nasal spray sCT, 63% failed to respond to the subcutaneous administration of 10 IU of sCT. In the treated group, a significant negative correlation has been found between the percentual changes in CTX from its baseline levels detected during the CLT, and a rate of changes in the femoral neck BMD (p<0.01). CONCLUSION: The CLT can be used as a tool to identify patients that respond to administration of CT, and will profit from a continued treatment with sCT.     

Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials

To determine the efficacy of teriparatide supplementation for improving bone mineral density (BMD) and fracture risk in postmenopausal osteoporosis and if effects vary with factors. We identified eight randomised controlled trials (n = 2388) using electronic databases, supplemented by a hand-search of the reference lists. All trials aimed to evaluate the efficacy of daily subcutaneous teriparatide injection in postmenopausal osteoporosis. The main outcomes were fracture risk and percentage change of BMD from baseline. Data were pooled by employing a random-effect model. In trials that reported BMD as an outcome, treatment was associated with an increase of bone mass of 8.14% [95% confidence interval (CI): 6.72-9.55%; eight trials, n = 2206] in spine and 2.48% (95% CI: 1.67-3.29%; seven trials, n = 1303) at the hip. In trials that reported fracture as an outcome, treatment was associated with a 70% risk reduction in vertebral fractures (risk ratio 0.30, 95% CI: 0.21-0.44; three trials, n = 1452) and 38% risk reduction in non-vertebral fractures (risk ratio 0.62, 95% CI: 0.44-0.87; three trials, n = 1842). The PTH treatment with total calcium intake more than 1500 mg was related to a significant increase in BMD gains at total hip (1.40% vs. 3.72%; p = 0.004). However, long-term duration did not appear to contribute to differences in responsiveness to teriparatide. Evidence supports the use of teriparatide in treatment of women with postmenopausal osteoporosis who are at risk for fracture. Further studies directly comparing concurrent therapy and calcium supplement with long-term duration are warranted.     

绝经后女性血清鸢尾素、25羟维生素D水平与骨代谢、骨质疏松的相关性

目的观察绝经后女性血清鸢尾素(Irisin)、25羟维生素D [25(OH)D]水平与骨代谢、骨密度(bone mineral density,BMD)、骨质疏松的相关性。方法选择2018年1月至2020年1月在河南科技大学第二附属医院健康中心体检的年龄>45岁的绝经后女性为研究对象,分为骨质疏松组(n=370)和非骨质疏松组(n=321),检测血生化、血清鸢尾素、25(OH)D、I型前胶原氨基端肽(procollagen typeⅠN-terminal propeptide,P1NP)和1型胶原羧基端肽β特殊序列(beta C-terminal cross-linked telopeptides of type icollagen,β-CTX)骨代谢指标,测量BMD,计算四肢骨骼肌指数(ASMI),并统计分析。结果绝经后女性骨质疏松组的鸢尾素[(16.53±4.46)ng/mL VS(20.32±4.52)ng/mL,P <0.001]和25 (OH)D [(23.66±5.46)ng/mL VS(31.42±4.93)ng/mL,P <0.001]水平均低于非骨质...     

Age-related changes in bone turnover markers and ovarian hormones in premenopausal and postmenopausal Indian women

This study characterizes age-related changes in bone turnover markers in relation to ovarian hormones. The data (N = 236) were divided into 5-year age bands and three groups: premenopausal (Group I, N = 139), perimenopausal (Group II, N = 30), and postmenopausal (Group III, N = 67). Age-related increases in mean parathyroid hormone (PTH), osteocalcin (OC), and collagen telopeptide (CTx) levels were observed. Women in Group II (N = 37) with osteopenia had lower levels of E1G (P<0.001) with normal FSH levels as compared to 50 women in the same group with normal bone mineral density (BMD). Their mean OC levels were reduced (P<0.05) and CTx levels were significantly elevated (P<0.01). The mean E1G levels were significantly lower (P<0.001) and mean CTx levels were significantly higher (P<0.001) in 30 perimenopausal women (Group II) compared to premenopausal women. In 28 postmenopausal women (group III) the mean BMD levels and E1G were significantly lower (P<0.001) with elevated FSH levels (P<0.001). Increased CTx levels (P<0.0001) reflected a higher rate of bone resorption. These observations suggest that perimenopausal women with low E1G, elevated FSH should be screened for osteoporosis, and it may be valid to combine simultaneous measurements of bone turnover markers with ovarian hormones when screening women at risk for osteoporosis.     

Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women

What is known and Objective: Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates. Methods: A randomized controlled trial was conducted from 2005 to 2009 in the University Malaya Medical Centre, Malaysia. Inclusion criteria: postmenopausal osteoporotic women diagnosed with osteoporosis with a T‐score≤?2·5 or who had a low‐trauma fracture and prescribed weekly alendronate/risedronate. Intervention participants received counselling on osteoporosis, risk factors, lifestyle modifications, goals of therapy, side effects and the importance of adherence. Adherence was assessed at months 3, 6 and 12, and persistence at month 12. Feedback on BTMs was provided at months 4 and 7. The control group received no counselling. Two BTMs were used: serum C‐terminal cross‐linking telopeptide of type I collagen (CTX‐I) and serum osteocalcin (OC). Main outcomes measured: medication adherence, BTMs and persistence. Results and Discussion: Intervention participants who received pharmaceutical care reported significantly higher medication adherence at 6 (P = 0·015) and 12 months (P = 0·047) compared with the control group; but this effect was not shown by the BTMs. This is probably due to the long effect of bisphosphonates in bone. A significant difference was found between serum CTX‐I and OC in identifying non‐responders to anti‐resorptive therapy (P < 0·001), indicating the usefulness of BTMs as an objective marker. However, pharmaceutical care did not affect persistence to osteoporosis therapy within a 1‐year period [log rank (Mantel–Cox) χ² = 0·496, P = 0·481]. The proportion of participants who were persistent with bisphosphonate therapy after 12 months was 89·8% and 87·0% in the control and intervention group respectively. What is new and Conclusion: The provision of pharmaceutical care improved medication adherence but not persistence. BTMs were not appropriate objective measures for assessing adherence to weekly bisphosphonates but were useful for identifying non‐responders to treatment within 3–6 months, much earlier than using bone mineral density. The study indicates that pharmacists have a role in improving medication adherence, but its long‐term effect on persistence warrants further studies with longer duration.     

Relation of estrogen receptor-α gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women

BACKGROUND. Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-α (ER α) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women. METHOD. We studied the influence of the ERα genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ERα gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ERα genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ERα genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ERα genotype. In conclusion, ER α polymorphism is associated with fall risk, especially with non-slip falls, in early postmenopausal Finnish women during the HRT. We have previously reported that, during HRT, women with the P allele have decreased fracture risk and that they may preferentially derive benefit from the positive effect of HRT on BMD. This suggests that the influence of ERα polymorphism may depend on the target tissue (bone versus the nervous system). CONCLUSIONS. In these early postmenopausal, non-osteoporotic and relatively healthy women, the increased fall risk associated with the PP genotype was not associated with increased fracture risk, possibly due to improved bone strength during the HRT although falls generally predispose to fractures.     

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

BACKGROUND: Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. METHODS: Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. RESULTS: Bone ALP decreased significantly from baseline at 3 months (P 相似文献   

Osteoprotegerin serum levels in women: correlation with age,bone mass,bone turnover and fracture status

Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast function and therefore plays an important role in bone remodelling. This study aimed to evaluate the clinical value of serum OPG. Do higher OPG serum levels reflect decreased bone resorption and perhaps higher bone mass in women? Serum OPG levels were measured in 177 healthy women (aged 17-85 years) and in 48 untreated patients (mean age 71 +/- 5) with established osteoporosis, and related to age, bone mass, markers of bone turnover and, in the case of patients with osteoporosis, to pre-existing vertebral fractures. In healthy women OPG levels showed a positive correlation with age (r = 0.25, p < 0.001) but not to bone mass or markers of bone turnover. In women with osteoporosis, however, there was a strong relationship between serum OPG and markers of bone turnover (serum c-terminal crosslinked telopeptides of thpe I collagen (sCTX): r = +0.82, p < 0.0001; osteocalcin (OC): r = +0.69, p < 0.0001), with patients who had higher levels of bone-turnover markers showing higher serum levels of OPG. After adjustment for bone mass and bone markers, patients with pre-existing vertebral fractures had significantly lower serum OPG levels than patients without fractures (57 +/- 8 vs. 97 +/- 10 pg/ml, [mean +/- SE], p < 0.01). The age-dependent increase of OPG as an antiresorptive factor may reflect an insufficient paracrine mechanism of bone cells to compensate for bone loss in older age. In patients with osteoporosis, however, OPG correlated strongly with markers of bone turnover; this may point toward a higher level of RANKL/OPG expression in these patients. Finally, low OPG serum levels seem to be associated with vertebral fractures. We hypothesise that low OPG levels in preset conditions of bone turnover may indicate a higher risk of fracture in patients with osteoporosis.     

Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women.

BACKGROUND: CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway. METHODS: The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein (CETP) in the serum of Chinese women was investigated. Serum concentrations of estradiol (E(2)), follicle-stimulating hormone (FSH), CETP and lipid profile were determined in 196 Chinese women (52 premenopausal with ages ranging from 18 to 40 years, 57 perimenopausal from 41 to 60 years, and 87 postmenopausal from 61 to 81 years). RESULTS: Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women (1.39+/-1.06, 2.36+/-1.50 and 2.31+/-1.25 mg/l, respectively, P<0.0001). Even in the women around the menopausal, CETP concentration in postmenopause was significantly lower than that in premenopause (1.93+/-1.33 vs. 3.42+/-1.35 mg/l, P<0.01). In addition, CETP concentration had a highly positive correlation with serum concentration of E(2) (r=0.243, P<0.001), while negative correlation of CETP concentration with serum concentration of FSH was found (r=-0.273, P<0.001). CONCLUSIONS: Estrogen may affect the concentration of CETP.