Etidronate and alendronate in the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis. DATA SOURCE: A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized. DATA SYNTHESIS: Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate. CONCLUSIONS: No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.     

Bone mineral density of metatarsus in hemiplegic subjects.

The cortical bone mineral density (BMD) of the first metatarsus was measured using computed x-ray densitometry in 84 hemiplegic subjects (35 men and 49 postmenopausal women) and 49 healthy age-matched controls (23 men and 26 postmenopausal women), and the determinants of paralysis-induced cortical osteopenia were investigated. In the hemiplegia group, ages were 63.9 +/- 9.8 yr (mean +/- standard deviation) for men and 66.6 +/- 11.0 yr for women. The duration of hemiplegia was 25.3 +/- 19.8 mo for men and 26.0 +/- 26.3 mo for women. The Brunnstrom stage (lower limb) was 4.0 +/- 1.1 for men and 3.8 +/- 1.4 for women. The walking ability, evaluated by walking score, was 3.6 +/- 1.3 (range, 1-5) for men and 3.2 +/- 1.5 (range, 1-5) for women. The time since menopause was 14.8 +/- 10.0 yr. The age and time since menopause were similar in the hemiplegia and control groups. On the paralyzed side, the BMD of men and women in the hemiplegia group was significantly lower than that of the control group on the nondominant side (by 6.1% and 11.6%, respectively). In hemiplegic men, Brunnstrom stage and walking score showed a significant positive correlation to the BMD (r = 0.418 and r = 0.349, respectively). In hemiplegic women, on the other hand, age, duration of hemiplegia, and years since menopause showed a significant negative correlation to the BMD (r = -0.260, r = -0.478, and r = -0.506, respectively), and Brunnstrom stage and walking score showed a significant positive correlation to the BMD (r = 0.526 and r = 0.406, respectively). These findings suggest that the determinant of metatarsal cortical BMD loss on the paralyzed side of the hemiplegic subject might be different according to gender. That is, although the degree of paralysis and walking ability could be a determinant of metatarsal cortical BMD loss on the paralyzed side of hemiplegic men, additional factors such as age, duration of hemiplegia, and years since menopause could play an important role in the determination of metatarsal cortical BMD loss in postmenopausal hemiplegic women.     

The evaluation of cardiovascular risk in postmenopausal women with osteopenia

The purpose of the study was to evaluate the prevalence of the most important cardiovascular risk factors in postmenopausal women in correlation with bone mineral density (BMD). A hundred and fifty postmenopausal women were included in a case control study. The subjects were distributed into three equal groups: normal bone mass; osteopenia; non-complicated osteoporosis. BMD was measured with lumbar double-energy X-ray absorptiometry. Cardiovascular risk factors were assessed. The level of triglycerides was significantly higher in patients with osteoporosis vs. subjects with normal BMD. Arterial hypertension and a 10-year fatal risk of more than 0% were significantly more prevalent in the group with normal BMD. Osteoporosis presents an independent cardiovascular risk factor. Postmenopausal women with decreased BMD should be considered to have a higher risk of cardiovascular events, because standard risk scales do not take BMD into account.     

Pamidronate increases bone mineral density in women with postmenopausal or steroid-induced osteoporosis

INTRODUCTION: We aimed to determine the efficacy and safety of a cyclic intravenous therapy with pamidronate in patients with postmenopausal or glucocorticoid-induced osteoporosis. METHODS: We enrolled 86 Austrian female patients with postmenopausal (n = 69, mean age 68.13 +/- 1.14) or glucocorticoid-induced (n = 17, mean age 66.89 +/- 2.03) osteoporosis defined as a T-score of < -2.5 for bone mineral density (BMD) of the lumbar spine L1-L4. Patients received a single intravenous dose of 30 mg pamidronate at 3 months intervals. The per cent change in BMD was primary, whereas the safety and the biological response were secondary endpoints. RESULTS: Seventy-six female patients (88%) completed study. Sixty patients received pamidronate therapy for the treatment of late postmenopausal osteoporosis and 16 patients received the same treatment for glucocorticoid-induced osteoporosis. At the end of the trial, lumbar spine (L1-L4) BMD increased significantly in patients with postmenopausal osteoporosis (P = 0.000067), whereas in patients with glucocorticoid-induced osteoporosis no significant change was observed (P = 0.724). The increase in the Ward's triangle BMD did not reach significance level in postmenopausal women receiving pamidronate (P = 0.0740). However, pamidronate treatment for glucocorticoid-induced osteoporosis resulted in a significant increase in Ward's triangle BMD (P = 0.0029). The efficacy of pamidronate treatment for postmenopausal osteoporosis was also reflected in a decrease in circulating biochemical markers for bone formation, including alkaline phosphatase and osteocalcin. In addition, pamidronate was well tolerated with no incidence of severe gastrointestinal events. CONCLUSION: Cyclic intravenous administration of pamidronate is well-tolerated therapy in postmenopausal osteoporosis, and increases spinal BMD. Randomized controlled studies with adequate number of patients are needed to test the efficacy of the compound in the treatment of glucocorticoid-induced osteoporosis.     

太极拳锻炼对绝经后女性骨密度的影响

目的探讨太极拳锻炼对绝经后女性骨密度、骨质疏松发生情况的影响以及不同太极拳锻炼年限对骨密度的影响。方法105 名绝经后女性分为太极拳组(n=54)和对照组(n=51),进行双能X线骨密度检测。结果太极拳组L1、L2、股骨干骨密度值高于对照组(P<0.05),L4、左股骨颈、左Wards 三角区骨密度明显高于对照组(P<0.01);太极拳组骨质疏松患病率(31.48%)略低于对照组(39.22%),但无显著性差异(P>0.05);练习太极拳5 年以上的绝经后女性在L1、L2、左股骨颈、左Wards 三角区、股骨干部位的骨密度值高于练习太极拳小于5 年的绝经后女性(P<0.05)。结论长期锻炼太极拳可改善绝经后女性骨密度水平,降低骨质疏松患病率。     

Risedronate: a new oral bisphosphonate

BACKGROUND: Bisphosphonates have been effective in the treatment of osteoporosis and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is approved by the US Food and Drug Administration for the prevention and treatment of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the treatment of Paget's disease of bone. OBJECTIVE: This article reviews current studies of risedronate in osteoporosis and Paget's disease of bone and, to the extent possible, compares risedronate with other bisphosphonates and other therapies. Information on the pharmacokinetics and adverse effects of risedronate, and the drug's use in other disorders, is also reviewed. METHODS: Clinical studies and review articles concerning the use of risedronate published in the English-language literature from 1966 through October 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts using the search terms risedronate and NE 58095. Recent clinical studies, review articles, and consensus statements regarding the use of other bisphosphonates were identified through searches of the same databases for this period using the search terms bisphosphonates, alendronate, osteoporosis, and Paget's disease of bone. RESULTS: The use of risedronate therapy in patients with postmenopausal osteoporosis has been shown to increase bone mineral density (BMD) and decrease the incidence of fractures compared with placebo. In glucocorticoid-induced osteoporosis, risedronate has been shown to increase BMD without having a consistently significant effect on the risk of fractures. Although there are no direct comparisons between bisphosphonates in glucocorticoid-induced osteoporosis, risedronate appears to be less effective than alendronate and more effective than etidronate in terms of effects on BMD and/or fracture risk. In Paget's disease of bone, risedronate has been reported to be more effective than etidronate in decreasing serum alkaline phosphatase levels and bone pain. Finally, risedronate has been associated with a lower incidence of gastric ulcers than alendronate. CONCLUSIONS: In terms of efficacy in the prevention and treatment of osteoporosis and the treatment of Paget's disease of bone, risedronate is comparable to alendronate, the other orally available bisphosphonate. It appears to have better gastrointestinal tolerability than alendronate and may be preferred for patients in whom this is a concern. However, direct comparative and pharmacoeconomic studies are necessary to determine risedronate's relative place in the therapy of osteoporosis and Paget's disease of bone.     

Optimizing the management of postmenopausal osteoporosis with bisphosphonates: the emerging role of intermittent therapy

BACKGROUND: The utility of bisphosphonates in the treatment of postmenopausal osteoporosis is compromised by the requirement of frequent oral administration or complex cyclic regimens. Recognition that simplified dosing regimens and reduced frequency of administration are important factors for improving adherence to therapy has led to the development of bisphosphonates with less frequent dosing regimens that aim to offer greater convenience. OBJECTIVE: This paper reviews the available data concerning the efficacy and tolerability of intermittent (less frequent than weekly) bisphosphonate dosing regimens for the treatment of postmenopausal osteoporosis, with particular focus on the potential implications for clinical management. METHODS: Papers on intermittent or cyclic bisphosphonate dosing regimens were identified by searching MEDLINE using the following terms: dose, dosing, dosage, or drug therapy; intermittent, cyclic, cyclical, weekly, monthly, month, week, administration, regimen, or schedule; and etidronate, alendronate, risedronate, zoledronate, neridronate, pamidronate, clodronate, ibandronate, or tiludronate. RESULTS: Because the currently available bisphosphonates differ in chemical structure, potency, and other physicochemical and biologic characteristics, comparable dose-free intervals may not be appropriate for all drugs. Several bisphosphonates have demonstrated efficacy in terms of an increase in bone mineral density (BMD) and a decrease in markers of bone turnover when administered intermittently. However, evidence of fracture benefit from a less frequent bisphosphonate dosing regimen was demonstrated recently. The nitrogen-containing bisphosphonate ibandronate was associated with a significant decrease in vertebral fracture risk when administered as an intermittent dosing regimen (P < 0.001 vs placebo). This study supports the concept that bisphosphonates such as ibandronate can be effectively administered less frequently than daily or weekly. CONCLUSIONS: Bisphosphonate therapy using intermittent schedules with between-dose intervals longer than 1 week is capable of reducing the risk of fracture, improving BMD, and suppressing biochemical markers of bone turnover. Planned and ongoing trials will determine the place of intermittent bisphosphonates in the treatment algorithm for postmenopausal osteoporosis.     

Etidronate

Intermittent cyclical therapy with etidronate increases bone mineral density in spine and hip, and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis, as well as steroid-induced osteoporosis. Seven years treatment with etidronate was reported to be safe, effective and well-tolerated. And additive effects of etidronate were documented in bone mineral density when hormone replacement therapy was combined. Recently many bisphosphonates have been commercially available in clinics. Although the potency of etidronate to inhibit bone resorption is relatively weak among those bisphosphonates, equal effects for others in osteoporosis can be obtained with the intermittent therapy, which is easy to be complied for the patients with less adverse events. In conclusion cyclical etidronate therapy is still important for osteoporosis therapy.     

Is treatment of early postmenopausal women with bisphosphonates justified?

The decision to treat women in the early postmenopausal period has come under scrutiny because of the low occurrence of fractures in this population and the possible lack of cost-effectiveness for individual patients. This article focuses on the potential use of bisphosphonates for the prevention and treatment of osteoporosis in the early postmenopausal period. Studies have determined that there is a relationship between bisphosphonate treatment and bone mineral density (BMD) gains, even in women in the early postmenopausal period without a diagnosis of osteoporosis. These patients receive benefit from treatment, including improvements in BMD levels and fracture protection. Using BMD scores, rates of bone turnover, and risk-based diagnostic criteria as part of the decision to initiate therapy may allow for the identification of an early postmenopausal patient population that would benefit from preventative therapy. This would improve the cost-effectiveness of using bisphosphonates for the prevention of osteoporosis in this population. The evaluation of women at risk for developing osteoporosis should include an assessment of both BMD scores and additional risk factors. Early postmenopausal women who are in a high-risk group should be considered candidates to receive bisphosphonate therapy.     

Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial.

Corticosteroid-induced osteoporosis is the most common secondary cause of osteoporosis. We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy x-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SE) changes in BMD of the lumbar spine by QCT and DXA in the PTH group were 35+/-5.5% and 11+/-1.4%, respectively, compared with a relatively small change of 1.7+/-1.8% and 0+/-0.9% in the estrogen-only group. The differences in mean percentage between the groups at 1 yr were 33.5% for the lumbar spine by QCT (P < 0.001) and 9.8% for the lumbar spine by DXA (P < 0.001). The changes in the hip and forearm were not significantly different between or within the groups. During the first 3 mo of PTH treatment, markers of bone formation increased to nearly 150%, whereas markers of bone resorption increased only 100%, suggesting an early uncoupling of bone turnover in favor of formation. These results suggest that parathyroid hormone dramatically increases bone mass in the central skeleton of postmenopausal women with corticosteroid- induced osteoporosis who are taking hormone replacement.     

绝经后妇女血清基质金属蛋白酶与骨转换生化指标及骨密度的关系

目的探讨绝经后妇女血清基质金属蛋白酶(MMP)-1和MMP-2与骨密度及骨转换生化指标之间的关系。方法采用酶联免疫吸附法测定297名48~80岁女性志愿者的血清MMP-1、MMP-2和血清骨碱性磷酸酶(BAP)、血清骨钙素(OC)及血清Ⅰ型胶原氨基末端肽(NTX),用双能X线吸收法测定腰椎正位1~4总体、股骨颈、华氏区、髋部总体的骨密度。结果MMP-1与骨密度及骨转换生化指标无明显相关性;MMP-2与骨密度呈较弱的负相关,校正年龄与体重指数后,MMP-2与股骨颈、髋部骨密度的相关性消失;MMP-2与BAP、OC、NTX正相关(P<0.01);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和骨量减少组(P<0.01)。结论绝经后妇女血清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。     

Beneficial effect of etidronate on bone loss after cessation of exercise in postmenopausal osteoporotic women

OBJECTIVES: To determine whether etidronate could prevent or restore bone loss after cessation of exercise in postmenopausal osteoporotic women. DESIGN: Thirty-five postmenopausal osteoporotic women were studied. Exercise consisted of daily brisk walking and gymnastic training. The changes in the lumbar bone mineral density measured by dual energy x-ray absorptiometry were assessed. RESULTS: One or two years of exercise increased the bone mineral density from the baseline. One year of cessation of exercise after 1 yr of exercise resulted in the loss of the bone mineral density gained through exercise. Two years of cyclical etidronate treatment from year 2 sustained the bone mineral density during 2 yr of cessation of exercise in the preventative etidronate treatment group and completely restored the loss of bone mineral density after 1 yr of cessation of exercise in the therapeutic etidronate treatment group. CONCLUSIONS: Cyclical etidronate treatment, when exercise is discontinued, seems to be beneficial for the prevention or restoration of bone loss after cessation of exercise in postmenopausal osteoporotic women. Although the present study has a small sample size, the results may be interesting, especially because they raise additional questions that could stimulate further research.     

补肾健骨胶囊对绝经后骨质疏松患者骨代谢相关指标的影响

目的观察补肾健骨胶囊对绝经后骨质疏松症炎性因子和骨代谢指标的影响。方法106例绝经后骨质疏松症患者随机分为两组,试验组服用补肾健骨胶囊,对照组服用钙尔奇D,6个月后检测血清中肿瘤坏死因子-α(TNF-α),白介素-6(IL-6),骨碱性磷酸酶(BLAP),骨钙蛋白(BGP),骨保护素(OPG),血浆抗酒石酸盐酸性磷酸酶(TRAP)和骨密度水平。结果用药前试验组和对照组年龄,骨代谢指标和炎性因子水平间差异无统计学意义(P＜0.05)。与用药前比较,试验组用药后血清IL-6和TNF-α水平显著下降,差异具有统计学意义(P＜0.01),而对照组用药后变化不明显(P＜0.05); 与对照组用药后比较,试验组用药后IL-6和TNF-α值降低,差异有统计学意义(P＞0.05)。试验组和对照组用药后BLAP,BGP,OPG和骨密度检测值较用药前升高,TRAP水平降低,差异均有统计学意义(P＞0.05);较对照组用药后,试验组OPG水平升高明显,差异具有统计学意义(P＜0.05),余骨代谢指标和骨密度两组间差异不明显(P＞0.05)。结论补肾健骨胶囊可改善绝经后骨质疏松患者骨代谢异常,在抑制炎性因子发生和提升OPG水平方面作用优于传统钙剂。     

绝经年限、体质量和人体质量指数与绝经后妇女的骨密度变化

背景绝经后妇女易于发生骨质疏松,不同年龄和体质量的人群,其骨量丢失的规律不同.目的分析年龄、绝经年限、绝经年龄、身高、体质量及人体质量指数对绝经后妇女骨密度的影响.设计以绝经妇女为研究对象,随机抽样检测.单位一所省级中医药研究院药品临床研究基地,一所大学医院骨科及一所大学骨伤系. 对象2000-09/2003-08福州地区自然绝经后妇女603例.方法采用随机抽样方法,记录患者年龄、绝经年限、绝经年龄、身高、体质量及人体质量指数,采用双能X射线骨密度仪检测腰椎和股骨颈、大转子及Ward's区骨密度,用SPSS软件相关回归分析.主要观察指标年龄、绝经年限、绝经年龄、身高、体质量和人体质量指数与骨密度的相关性及回归方程.结果绝经后妇女的年龄、绝经年限、体质量和人体质量指数与腰椎、股骨颈、大转子及Ward's区骨密度的相关性十分显著;低体质量组骨密度明显低于超体质量组(P＜0.01);影响腰椎、大转子骨密度的主要因素为年龄和体质量,影响股骨颈骨密度的重要因素为绝经年限和体质量.影响腰椎骨密度的因素依次为年龄、体质量和绝经年龄,回归方程y=0.927-0.009 3X1+0.003 7X2+0.004X3,影响股骨颈骨密度的因素依次有绝经年限、体质量和绝经年龄,回归方程y=0.687-0.008 1X1+0.004 8X2-0.003 4X3,影响大转子骨密度的因素依次有年龄、体质量和绝经年限,回归方程y=0.591-0.003 8X1+0.004 2X2-0.002 4X3,影响Ward's区骨密度的因素依次有年龄、人体质量指数和绝经年限,回归方程y=0.686-0.007 2X 1+0.013 6X2-0.004 6X3.结论绝经后女性随着年龄的增大,其腰椎和髋部的骨密度呈下降趋势,对于体瘦者,患骨质疏松的危险性要大于正常体质量组及肥胖组.     

Activity or mass concentration of bone-specific alkaline phosphatase as a marker of bone formation.

BACKGROUND: Recently published data identified bone-specific alkaline phosphatase (BALP) as a good marker of bone formation in different bone diseases and osteoporosis. Two methods are available for BALP determination: one measures enzyme activity, the other its mass concentration. We compared results for BALP activity and its mass concentration in a group of 88 healthy pre- and postmenopausal women to identify which is a more useful marker for detecting early menopausal bone remodelling changes. METHODS: We measured BALP activity and BALP mass concentration in relation to femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and some other widely used bone markers: osteocalcin (OC), procollagen type I N-terminal propeptide (PINP) and serum C-terminal telopeptide cross-links of type I collagen (CTx) in serum samples from 50 premenopausal (age 45.9+/-4.6 years) and 38 postmenopausal (age 54.4+/-4.5 years) women. RESULTS: Healthy postmenopausal women exhibited 34.2% (p<0.01) and 27.3% (p=0.000) higher levels of BALP activity and mass concentration than premenopausal women, respectively. At the same time, FN and LS BMD were not significantly different between the groups. CTx values were significantly higher in postmenopausal women (p=0.018), while OC and PINP were not. We observed significant correlation between BALP activity and mass concentration (r=0.85, p<0.01). The correlation between BALP activity and FN BMD or LS BMD was insignificant. BALP mass correlated significantly with LS BMD (r=-0.370, p=0.033) but not with FN BMD. As expected, we proved a significant positive correlation for both BALP methods with the other bone markers measured in our study. CONCLUSIONS: Postmenopausal women have slightly higher bone turnover. Since LS and FN BMD were not significantly lower in our group of healthy postmenopausal women, but BALP and CTx were markedly higher, we suggest that measurements of BALP and CTx might be useful as early markers of higher bone turnover. Finally, our results did not show any differences between the clinical utility of BALP activity and BALP mass concentration measurements.     

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.     

绝经后妇女血清基质金属蛋白酶-9和基质金属蛋白酶抑制因子-1的表达及其意义

目的:探讨绝经后妇女血清基质金属蛋白酶-9和基质金属蛋白酶抑制因子-1在不同骨密度条件下的变化,为临床骨质疏松诊断与治疗提供依据。方法:用Challenge双能X线骨密度仪测量骨密度。选择绝经后妇女64例,分为正常对照组21例(骨密度正常)、低骨量组20例、骨质疏松组23例,并用酶联免疫吸附试验测定各组血清基质金属蛋白酶-9和基质金属蛋白酶抑制因子-1的浓度。结果:绝经后女性血清基质金属蛋白酶-9水平随骨密度的降低呈现升高趋势;低骨量组、骨质疏松组基质金属蛋白酶抑制因子-1水平与对照组比较无统计学意义;正常对照组、低骨量组、骨质疏松组基质金属蛋白酶-9与基质金属蛋白酶抑制因子-1的比率依次升高,基质金属蛋白酶-9与基质金属蛋白酶抑制因子-1的比率失调。结论:绝经后妇女血清基质金属蛋白酶-9水平升高及基质金属蛋白酶-9与基质金属蛋白酶抑制因子-1的比率失调可作为骨质疏松症监测的临床指标之一;应用基质金属蛋白酶-9和基质金属蛋白酶抑制因子-1与骨密度的关系来诊断骨质疏松症具有一定的临床意义。     

Efficacy and tolerability of alendronate once weekly in Asian postmenopausal osteoporotic women

BACKGROUND: Osteoporosis has become a major health problem worldwide, and the incidence is rising in Asian countries. The aminobisphosphonates are potent inhibitors of bone resorption and are currently the mainstay of treatment for postmenopausal osteoporosis. Dosing frequency will likely affect tolerability and adherence to treatment. OBJECTIVE: To assess the tolerability and efficacy of a once-weekly aminobisphosphonate preparation in improving bone mineral density (BMD) and bone turnover markers in osteoporotic Asian women. METHODS: Chinese postmenopausal women with osteoporosis were randomized to receive either alendronate 70 mg once weekly plus calcium carbonate 500 mg daily (n = 29) or calcium carbonate 500 mg daily (n = 29) for one year. BMD was measured by dual energy X-ray absorptiometry. Markers of bone formation and bone resorption included plasma total alkaline phosphatase and urine N-telopeptides. RESULTS: Treatment with alendronate 70 mg once weekly for one year resulted in significant BMD improvement of 6.1% at the spine, 5.6% at the femoral neck, and 3.5% at the total hip. There was no significant change in the BMD values in the calcium group (spine 1.4%, femoral neck -0.2%, total hip 0%). The BMD response in the alendronate group was significantly different from that in the calcium group at all time points, and the difference was detectable as early as after 3 months of treatment (ANOVA p < 0.001). The changes remained significant after adjusting for age, age at menarche, and years since menopause (p < 0.001). Similarly, the reductions in bone markers at 12 months were significantly different between the 2 treatment groups (plasma total alkaline phosphatase: alendronate 27.9%, calcium 5.4%; urine N-telopeptide: alendronate 55.6%, calcium 11.2%; both p < 0.001). The alendronate regimen was well tolerated, without significant adverse events. CONCLUSIONS: The results confirmed that once-weekly alendronate was efficacious in increasing BMD and reducing bone turnover and was well tolerated in Asian women.     

Teriparatide: a review

BACKGROUND: Traditionally, the management of osteoporosis in men and women has included the use of antiresorptive agents in combination with calcium and vitamin D supplementation. The mechanism of action of teriparatide is unique in that it possesses anabolic properties and therefore builds bone. Since the approval of teriparatide in the United States in 2002, a great deal of interest regarding its use in osteoporosis has developed. OBJECTIVES: This article reviews the information available on the new recombinant human parathyroid hormone teriparatide (hPTH [1-34]), including its clinical pharmacology, mechanism of action, pharmacokinetic properties, clinical efficacy, safety profile, potential drug interactions, contraindications and warnings, dosage and administration, and pharmacoeconomics. METHODS: The articles included in this review were identified through searches of PubMed and MEDLINE (1966-December 2003) and International Pharmaceutical Abstracts (1970-December 2003). Search terms included teriparatide, Forteo, recombinant human parathyroid hormone (1-34), and osteoporosis. The references of the identified articles were reviewed for additional publications. Specific product information was also obtained from the manufacturer of teriparatide. RESULTS: Teriparatide has been studied in postmenopausal women with osteoporosis, drug-induced osteoporosis (specifically, corticosteroid-induced osteoporosis), and men with osteoporosis. The data available from various clinical trials have shown an increase in both bone mineral density (BMD) and bone mineral content (BMC) with the use of teriparatide compared with placebo. One study found that women treated with the 20-microg dose and the 40-microg dose were 35% and 40%, respectively, less likely to have one or more new nonvertebral fractures compared with placebo (P = 0.02). Another study compared the use of daily teriparatide 40-microg injections versus oral daily alendronate. Results showed that the incidence of nonvertebral fractures was significantly lower in the teriparatide group than the alendronate group (P < 0.05). A study using 20- and 40-microg daily injections of teriparatide was performed in men with osteoporosis. There was a statistically significant increase in lumbar spine BMD of 5.9% in the 20-microg group and 9.0% in the 40-microg group (both, P < 0.001). In the femoral neck, a 1.5% increase in BMD occurred in the 20-microg group (P = 0.021) and a 0.9% increase in the 40-microg group (P < 0.001). A limited number of studies are available assessing the combination of antiresorptive medications and teriparatide; however, the available data suggest that the effects of teriperatide do not require prior stimulation of bone resorption. CONCLUSIONS: Teriparatide has been shown clinically to improve BMD and BMC in postmenopausal women and in men. Because of its anabolic capabilities, teriparatide can be used as an alternative to the traditional therapies that are currently available for the treatment of osteoporosis, with scheduled monitoring for adverse effects such as hypercalcemia and urinary calcium excretion. In 1 study, mild hypercalcemia was seen most often 4 to 6 hours after SC injection of teriparatide before returning to normal. Urinary calcium was observed to increase by 30 mg/d (0.75 mmol/d) with teriparatide.     

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...