Vitamin K2 Therapy for Postmenopausal Osteoporosis

Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K₂ that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.     

The Burden of Osteoporosis and the Case for Disease Management

Currently, osteoporosis, defined as low bone mineral density (BMD), affects 30% of postmenopausal women and 8% of men >50 years old in Western society and these percentages are likely to increase as our elderly population expands. Osteoporosis-related fractures increase with age and reductions in BMD, with the greatest increase in hip, followed by vertebral, and then wrist fractures. Osteoporosis is associated with significant mortality and for each 1 SD decrease in BMD there is a 1.5-fold increase in mortality risk. Following a hip fracture, 25–30% of patients will die within 3–6 months and in some populations hip fractures account for 1.5% of all deaths. Osteoporosis and related fractures are associated with significant morbidity, with loss of independence, psychological effects, and an overall decreased quality of life.The current financial cost of osteoporosis in the US is $US14 billion and in the UK just over £1 billion, and these costs will increase 3- to 8-fold over the next 50 years. Treatments are available that have been shown to significantly increase BMD, decrease bone turnover, and as a result decrease fracture incidence. For reductions in both vertebral and fracture, the evidence is strongest for the use of the bisphosphonates alendronate and risedronate; while for vertebral fracture, effective treatments include raloxifene, etidronate, calcitonin, and calcium plus vitamin D. Recent data suggest that hormone replacement therapy (HRT) can prevent hip and vertebral fractures, but long-term use, or commencement in elderly women of some continuous combined preparations, is no longer recommended.It has been recognized that bone turnover and bone quality contribute to fracture risk and, therefore, biochemical assessment of bone resorption and formation may increase the clinical and cost effectiveness of treatment. Using a conservative estimate of fracture reduction (35%) over a 5-year period, an intervention costing $US500 (£333) per year is cost effective when targeted to women with osteoporosis who are ≥65 years of age. It has been calculated that the lower the intervention cost and the higher the effectiveness of treatment the lower the age at which the treatment would be cost effective. The increasing healthcare burden and effective treatments make osteoporosis an excellent candidate for disease management programs.     

Treating osteoporosis

The aims of treatment of established osteoporosis are the alleviation of symptoms and reduction of the risk of further fractures. Currently available drugs are used to prevent further bone loss and can reduce the risk of further fractures by up to 50%. Drugs to increase bone mass inhibit bone resorption or stimulate bone formation. Most drugs approved for use in osteoporosis inhibit bone resorption, but some of these (e.g. hormone replacement therapy (HRT), bisphosphonates) increase BMD by 5-10% over the first 2 years of treatment. However, this contribution notes that drug treatments should be monitored by BMD, because some patients fail to respond to certain drugs. There is also evidence that the rate of bone loss is accelerated once treatment is stopped; it is therefore important to measure BMD or bone turnover markers after stopping treatment.     

Osteoporosis and African American women

The incidence of osteoporosis and related fractures in African American women is half that of Caucasian women. African American women who sustain osteoporosis-related fractures have increased disability and decreased survival. Given the exponential increase in hip fracture rate among African American women over the age of 70 years, the risk of osteoporosis among this population may be underestimated. This review focuses on racial differences in women's bone mineral density (BMD) and bone metabolism and on various explanations for these observed differences. Environmental risk factors for osteoporosis and related fractures among African American women and modalities for prevention and treatment of osteoporosis are discussed. African American women begin menopause with higher BMD and have lower rates of women's bone loss after menopause, which account for their decreased incidence of osteoporosis and related fractures. The risk factors for osteoporosis among African American women are similar to those found in Caucasian women. Lifestyle interventions, such as calcium and vitamin D supplementation, smoking cessation, and increased physical activity, should be encouraged to enhance peak bone mass and to decrease bone loss. These interventions and other treatment modalities, such as hormone replacement therapy, bisphosphonates, and selective estrogen receptor modulators, should be studied further in African American women.     

染料木素对铅中毒致SD大鼠骨质疏松的保护作用

目的 通过检测铅中毒大鼠股骨的骨量、生物力学指标以及病理骨形态计量等指标,阐明铅暴露对大鼠骨质疏松的影响,并进一步研究染料木素作为防治铅暴露致大鼠骨质疏松药物的可行性,为铅中毒的效应研究以及防治提供实验依据.方法 大鼠醋酸铅饮水染毒建立模型,染料木素通过灌胃的方式进行给药干预.通过原子吸收分光光度计检测各组SD大鼠股骨...     

64排128层螺旋CT骨密度测量在椎体骨质疏松性骨折研究领域的进展

目的:本研究旨在应用64排128层螺旋CT进行骨密度测量,探讨椎体骨质疏松与骨折的相关性。方法:选取2011年1月至2012年12月在我院就诊的50岁以上中、老年病例200例,进行骨密度(BMD)测定,分析其定量CT(QCT)脊柱检查资料,将骨折病例作为研究组、无骨折病例作为对照组,然后进行统计学处理。结果:骨折组的椎骨BMD明显低于无骨折组,BMD与椎体骨折呈负相关性,BMD越低,骨质疏松的程度越严重,发生骨折的几率就越高。结论:64排128层螺旋CT骨密度测定是一种非常准确的骨密度测量方法,利用此种检查方法可早期发现骨质疏松,并积极进行干预,从而预防椎体骨折的发生。     

Effect of anti-osteoporosis agents on the incidence of vertebral fractures

In the early nineties of the last century, increase in bone mineral density (BMD) was usually the primary endpoint in studies observing the effect of anti-osteoporotic medication. Recently, several large studies have been published with the number of new vertebral deformities as the primary endpoint. This should be preferred, since fractures are generally associated with clinical signs and symptoms, while changes in BMD are not. In all these studies of the effects of alendronate, risedronate, raloxiphen and calcitonin in postmenopausal women with osteoporosis there was a striking discrepancy between a small increase in BMD of the lumbar spine, varying from +2 tot +8%, and a much larger reduction in the number of patients with new vertebral fractures: -36 to -49%. This difference could be related to an effect on bone quality, an independent effect on bone resorption, or to technical limitations of BMD measurements that underestimate true effects of antiresorptive therapy. The number of patients needing to be treated to prevent one fracture depended on background risk and on the effectiveness of the therapy.     

Update on osteoporosis management in long-term care: focus on bisphosphonates

Osteoporotic fractures are potentially devastating and associated with high morbidity and substantial economic burden. Residents of long-term care facilities are at greater risk of osteoporosis and its related fractures than those living in the community, yet osteoporosis is underdiagnosed and undertreated in these settings. Bisphosphonates are approved by the Food and Drug Administration for the treatment and prevention of osteoporosis in postmenopausal women. As a class, bisphosphonates have been shown to increase bone mineral density, decrease the markers of bone resorption, and reduce the risk of osteoporotic fractures. The 3 approved bisphosphonates are alendronate, risedronate, and ibandronate. Alendronate and risedronate are dosed daily or weekly and ibandronate, the most recently approved bisphosphonate, has been approved for monthly oral dosing or as an intravenous formulation to be given intermittently (every 3 months). In addition, other products with different mechanisms of action are in the pharmaceutical pipeline and may offer additional management options.     

大豆异黄酮加钙和骨胶原对PMOP骨的保护作用

目的探讨大豆异黄酮与钙和骨胶原的共同作用对绝经后骨质疏松症 （ postmenopausal osteoporosis，PMOP）骨密度及生物力学影响。方法设一假手术组；将去卵巢大鼠分为阴性对照组，高、中、低剂量组和碳酸钙对照组，分别给予基础饲料和不同剂量受试物以及碳酸钙，12周后进行骨密度和生物力学测定。结果受试物能增加骨密度及改善部分骨生物力学性能。结论大豆异黄酮与钙和骨胶原组合的受试物可改善雌激素缺乏所致骨质疏松症的骨质性能。     

Bisphosphonates in the prevention and treatment of glucocorticoid-induced osteoporosis

OBJECTIVE: To summarize the literature concerning the use of bisphosphonates in the prevention and treatment of corticosteroid-induced osteoporosis and make recommendations concerning the proper use of these agents. SEARCH STRATEGIES: We conducted a literature search to identify studies in the English language concerning the use of bisphosphonates in the prevention or treatment of corticosteroid-induced osteoporosis using the MEDLINE, CURRENT CONTENTS, and HEALTHSTAR electronic databases, bibliographies of selected citations, and recent meeting abstracts. SELECTION CRITERIA: We included randomized controlled trials evaluating the use of oral bisphosphonates in adults by central dual X-ray absorptiometry. DATA COLLECTION AND ANALYSIS: We assessed the methodologic quality of the trials using the Jadad criteria. Data were collected concerning bone mineral density (BMD) changes in multiple areas, fracture rates, safety, and tolerability. MAIN RESULTS: Bisphosphonates generally increased BMD at the lumbar spine. Data were less clear concerning changes in the femoral area. Little information exists about the ability of bisphosphonates to reduce fracture risk in patients with corticosteroid-induced osteoporosis. Postmenopausal women seemed to receive the most benefit. CONCLUSIONS: Bisphosphonates significantly increased BMD in patients at risk for corticosteroid-induced bone loss. However, there is a sparsity of data concerning the ability of these agents to affect the clinically important outcome of fracture rate reduction, especially among premenopausal women in whom fractures are rare within the first year or 2 of exposure to corticosteroids. Long-term studies powered to detect fracture risk reduction are needed as well as comparative trials with bisphosphonates and other agents.     

广州市健康妇女骨量影响因素的初步探讨

目的:探讨影响骨质疏松的有关因素,为妇女骨质疏松症的防治提供科学依据。方法:选取在广州市居住10年以上的妇女281例,以问卷形式进行可能影响妇女骨量的有关因素调查,并测量骨密度,分析妇女骨量的影响因素。结果:腰椎BMD值与体重、BMI、运动情况成显著正相关,与生育次数成显著负相关;沃氏(Ward's)三角区的BMD值与身高、体重、BMI、营养、运动呈显著正相关,与生育次数呈显著负相关。结论:体重、营养、运动对妇女骨量有保护作用。     

儿童糖皮质激素性骨质疏松的防治

糖皮质激素在儿科疾病中应用广泛,长期应用糖皮质激素可导致骨密度减低及骨折等。在成人,存在管理糖皮质激素性骨质疏松症的循证指南,儿童糖皮质激素性骨质疏松症也越来越受到儿科医师的重视,但有关儿童的信息还是非常少,本文主要对儿童糖皮质激素性骨质疏松的预防和治疗进行综述。     

补钙对大鼠峰值骨量形成和预防骨质疏松的作用

目的 :　探讨补钙对峰值骨量的影响及对绝经后骨质疏松发生的预防作用。方法 :　选用雌性大鼠喂给不同钙含量的饲料至 1 0 mo龄 ,半数动物断头处死 ,取股骨进行相关检测 ,了解不同钙摄入量对骨峰值的影响。半数动物行卵巢切除术 ,喂饲 1 0 w后断头处死 ,取股骨进行有关检测 ,了解不同峰值骨量对骨质疏松的预防作用。结果 :　高钙摄入组峰值期大鼠股骨骨密度、骨重、骨长度、骨皮质厚度和股骨最大载荷、骨应变量等值均较低钙摄入组高 ;去卵巢后各组骨密度均降低 ,但高钙摄入量大鼠股骨骨密度比低钙摄入量大鼠的高。结论 :　钙摄入量的增加能有效提高峰值骨量 ,较高的峰值骨量能延缓骨质疏松的发生和降低骨折发生的危险性     

中国四地区一般人群骨密度抽样研究

目的了解我国一般人群骨密度正常参考值.方法采用双能X线骨密度仪,对中国四地区20岁以上一般人群随机抽样2331例进行测量.结果确定男女不同年龄组腰椎及股骨近端骨密度正常参考值及骨峰值.结论进一步得出筛选治疗对象骨密度参考值及骨质疏松症诊断骨密度参考值.     

Vertebral compression fractures at the onset of acute lymphoblastic leukemia in a child

A child with acute lymphoblastic leukemia, spinal osteoporosis with vertebral compression fractures, and hypercalcemia appearing early in the course of the hematologic disease was followed for two and a half years. Bone mineral density (BMD), measured by single photon absorptiometry at the radial shaft, was within normal limits for age and sex. However, x-rays of vertebrae and vertebral BMD, measured by dual photon absorptiometry, showed marked demineralization. Despite leukemic remission, the spinal osteoporosis became worse and the patient required aggressive treatment for eight months. Treatment included 50 units of calcitonin subcutaneously every other day, 1,000 mg/day of oral calcium, and 3,000 IU/day of vitamin D. The back pain disappeared quickly, and laboratory controls showed a significant diminution of bone turnover. No new compression fractures occurred. Eighteen months later, the patient continued in remission and menarche had occurred. Dual photon absorptiometry revealed a significant "catch up" of the lumbar spine BMD. X-ray examination showed a marked remodeling of the vertebral bodies. BMD measurements in this child indicate that bone loss affected the trabecular bone compartment or occurred only at active bone marrow sites. The rapid clinical amelioration and objective biochemical, densitometric, and radiologic evidence of bone improvement warrant further clinical trials on similarly affected patients.     

Management of Postmenopausal Osteoporosis

Postmenopausal osteoporosis is a very common disease, and approximately half of all women aged >50 years will experience an osteoporotic fracture during the remainder of their lifetime. The predominant cause of postmenopausal osteoporosis is the decline in estrogen levels, which causes an increase in bone turnover, and results in a loss of bone mass throughout the entire skeleton. Fragility fractures, either vertebral or nonvertebral, have a considerable adverse effect on quality of life in women with osteoporosis and place a significant burden on society in terms of healthcare costs.Management of postmenopausal osteoporosis includes alteration of modifiable risk factors (e.g. lifestyle and propensity to fall), ensuring adequate calcium and vitamin D intake, and pharmacological treatment to decrease fracture risk by slowing or preventing bone loss and preserving bone strength. Raloxifene (Evista®), a selective estrogen receptor modulator that partially mimics the effects of estrogen on bone and lipid metabolism and acts as an antiestrogen in the breast and endometrium, is indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene increases bone mineral density at vertebral and nonvertebral sites, and decreases the risk of vertebral fracture to a similar extent to the bisphosphonates alendronate and risedronate. However, effects on nonvertebral fracture risk, including the risk of hip fracture, have not been observed.Raloxifene appears to reduce breast cancer risk (in women at average risk) and cardiovascular risk (in women at increased risk) without stimulating the endometrium, and does not cause vaginal bleeding or breast pain. However, the drug causes hot flashes in some women, and increases the risk of venous thromboembolic events by about the same amount as hormone replacement therapy (HRT).In economic models, raloxifene is cost effective compared with no treatment, HRT, calcitonin, or alendronate for the prevention or treatment of postmenopausal osteoporosis.In conclusion, raloxifene is a valuable and cost-effective therapy for preventing the progression of osteoporosis and for reducing vertebral fracture risk in osteoporotic postmenopausal women. The tendency for raloxifene to cause hot flashes, and its apparent lack of effect on hip fracture risk, may preclude its use in women with vasomotor symptoms and in patients at high risk for hip fracture. Results from large ongoing trials are needed to confirm the effects of raloxifene on breast cancer and cardiovascular disease. However, the effects of raloxifene on breast cancer and cardiovascular risk without stimulating the endometrium make the drug an attractive therapy for the prevention and treatment of postmenopausal osteoporosis.     

Zinc Pharmacotherapy for Elderly Osteoporotic Patients with Zinc Deficiency in a Clinical Setting

Although there have been reported associations between zinc and bone mineral density (BMD), no reports exist on the effect of zinc treatment in osteoporotic patients. Therefore, we investigated the efficacy and safety of zinc pharmacotherapy in Japanese elderly patients. The present investigation included 122 osteoporotic patients with zinc deficiency, aged ≥65 years, who completed 12 months of follow-up. In addition to standard therapy for osteoporosis in a clinical setting, the subjects received oral administration of 25 mg zinc (NOBELZIN^®, an only approved drug for zinc deficiency in Japan) twice a day. BMD and laboratory data including bone turnover markers were collected at 0 (baseline), 6, and 12 months of zinc treatment. Neither serious adverse effects nor incident fractures were seen during the observation period. Serum zinc levels were successfully elevated by zinc administration. BMD increased significantly from baseline at 6 and 12 months of zinc treatment. Percentage changes of serum zinc showed significantly positive associations with those of BMD. Bone formation markers rose markedly from the baseline values, whereas bone resorption markers displayed moderate or no characteristic changes. Additive zinc supplementation may contribute to BMD augmentation ensuing the prevention of fracture occurrence in elderly osteoporotic patients with zinc deficiency.     

Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures

According to the data of a fracture intervention trial, in women aged 55-80 years with vertebral fractures or osteoporosis diagnosed by bone mineral density measurement, treatment with the bisphosphonate alendronate prevented hip fractures with numbers-needed-to-treat within 5 years of treatment of 46 and 66, respectively. In a large risedronate hip fracture study, this new bisphosphonate only showed a beneficial effect in women aged 70-79 years with moderately severe osteoporosis as judged by femoral neck T-score, when one or more vertebral fractures were present at the start of the treatment. The number-needed-to-treat was 29. However, in women aged over 80 years and who were selected predominantly on the basis of clinical risk factors for hip fracture, no effect was found with this drug on hip fracture rate, suggesting that most were not osteoporotic and/or that the clinical risk factors used did not have the clinical utility in identifying hip fracture risk. Other factors besides osteoporosis may play a more important role in causing hip fracture in this elderly group. Diagnosis of osteoporotic vertebral fractures in women aged 70-79 years is predictive of not only new vertebral fractures but also of hip fractures, and could therefore form an indication for drug treatment.     

老年妇女骨折与骨密度关系的探讨

目的根据本院骨折住院病人骨密度(bone mineral density,BMD)的改变探讨老年椎骨骨折与BMD的关系,为老年人椎骨骨折的防治提供理论依据。方法自2007年1月-2009年1月,共收集椎骨骨折妇女48例(55～70岁),健康体检未骨折妇女21例(56～72岁)。采用双能X线骨密度仪Lunar-DPXIQ测定腰椎正位(L2-4)BMD降低情况。结果骨折组腰椎BMD低于对照组,差异有统计学意义(P0.05)。结论老年妇女椎骨骨折的发生与腰椎BMD的降低明显相关。     

老年骨质疏松患者生物型与骨水泥型全髋关节置换术临床疗效对比分析

目的:总结分析老年骨质疏松患者应用生物型全髋关节置换术及骨水泥型全髋关节置换术的疗效。方法:2002年3月至2008年4月对94例严重骨质疏松的髋部骨折患者分别根据骨折类型及骨密度测量结果选择生物型及骨水泥型全髋关节置换术,术后随访,进行髋关节功能、疼痛与关节活动度测定及髋部影像学检查,采用Harris评分标准对不同固定方式的临床疗效进行回顾性分析。结果:老年骨质疏松的股骨颈骨折、粗隆间骨折患者经全髋关节置换术,患者术后均进行随访,骨水泥型假体与生物性假体相比的临床疗效存在明显差异(P<0.01)。结论:对于老年骨质疏松患者行全髋关节置换术,骨水泥型术后疗效优于生物型。