That old hip. The osteoporosis process

Osteoporosis is a major health concern that will contribute to an increasing number of hip fractures as the population ages. Researchers are continuing to evaluate the role that decreased level of estrogen at menopause and prolonged calcium insufficiency play in the development of osteoporosis. In addition, many health care recommendations are aimed at maximizing peak bone mass and preventing bone loss to decrease the chance of hip fracture. New studies are evaluating the efficacy of experimental medications to rebuild bone mass once osteoporosis has developed. Current prevention guidelines include adequate calcium and vitamin D intake and moderate exercise. At menopause, estrogen replacement therapy is recommended for those younger than 50 years or considered at high risk for developing osteoporosis. All people are encouraged to decrease the risk of fracture by evaluating their home environment for hazards that might contribute to falls. Nursing needs to develop new strategies and interventions to educate the public about osteoporosis, improve the quality of life for persons with osteoporosis, and decrease the osteoporotic hip fracture mortality rate. Will it rise to the challenge?     

Pharmacologic and nonpharmacologic management of osteoporosis

Fractures that occur as a result of osteoporosis are associated with significant morbidity, mortality, and cost. A treatment regimen consisting of both nonpharmacologic and pharmacologic interventions can be used to decrease the risk of fracture. Nonpharmacologic interventions include calcium and vitamin D supplementation, weight-bearing exercise, muscle strengthening, and fall prevention. Pharmacologic options include: the bisphosphonates, estrogen therapy, raloxifene, salmon calcitonin, and the anabolic agent teriparatide. Although bone mineral density is used clinically to diagnose osteoporosis, it is of limited value when evaluating pharmacologic treatment; the primary indicator of treatment efficacy is fracture risk reduction. The bisphosphonates are the preferred therapy for osteoporosis. Studies have demonstrated that in postmenopausal women, both risedronate and alendronate are associated with reductions in vertebral and nonvertebral fracture risk. The newest approved bisphosphonate, ibandronate, reduces vertebral fracture risk. Studies also support a reduction in fracture risk when alendronate and risedronate are used in men with osteoporosis and patients with corticosteroid-induced osteoporosis. When used appropriately, the bisphosphonates are well tolerated. Estrogen and raloxifene decrease fracture risk in postmenopausal women with osteoporosis but are associated with thromboembolic events. Use of estrogen therapy is also limited by concerns about the safety of this type of therapy. Although the anabolic agent teriparatide is associated with reductions in vertebral and nonvertebral fractures, its use has been limited by the necessity of subcutaneous administration and its cost relative to other agents. Regardless of which treatment regimen is selected, health care providers need to emphasize the importance of compliance and adherence to improve persistence with therapy, and subsequent fracture reduction efficacy.     

Estrogen therapy during menopause and the treatment of osteoporosis

Estrogen remains the single most effective agent in the treatment of menopausal symptoms and prevention of bone loss. This article focuses on the use of estrogen therapy during menopause and the pharmacotherapy of osteoporosis. Risks and benefits of hormonal therapy and regimen selection for menopausal women are discussed. The second section of the article focuses on current treatment strategies for osteoporosis.     

Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines.

The authors, all physicians involved in clinical research on bone and practicing clinicians, propose practical guidelines for identifying persons with osteoporosis or those at high risk of developing the disease and for managing patients who may benefit from therapy. These guidelines are based on an analysis of peer-reviewed articles published before November 1998. A flowchart of women who might benefit from treatment is provided, including clinical presentation (recent fracture of the spine, hip, or other bone or no fracture; risk factors for osteoporosis); relevant investigations (bone mineral density measurement and laboratory tests required for the differential diagnosis); and therapeutic management (general measures such as calcium and vitamin D supplementation and specific pharmacologic interventions such as estrogen, bisphosphonates, intranasal calcitonin, raloxifene, fluoride salts, and other compounds that have been assessed in randomized clinical trials). The strongest evidence for antifracture efficacy (reduction of vertebral and nonvertebral fracture risk) was observed with alendronate.     

Estrogen receptors and human disease

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.     

老年骨质疏松症现状及进展

老年性骨质疏松症以骨矿含量下降,骨微细结构破坏为病理特征。男性峰值骨量高于女性,出现骨丢失的年龄迟于女性,而且雄激素水平的下降是“渐进式”,而非“断崖式”,故老年男性骨丢失的量与速度都低于老年女性,老年男性骨质疏松的程度轻于女性。老年骨质疏松症的诊断基于全面的病史采集、体格检查、骨密度测定、影像学检查(X线及QCT)及必要的生化测定。在使用基础用药的基础上(钙剂和维生素D),治疗骨质疏松症的药物可分为抑制骨吸收药物和促骨形成药物。抑制骨吸收药物包括双膦酸盐、雌激素替代疗法、选择性雌激素受体调节剂(SERM)、地舒单抗、降钙素等等。促骨形成药物包括甲状旁腺激素(PTH)类似物和骨硬化蛋白抑制剂。序贯和组合使用抗骨质疏松药物,例如从促骨形成药物转换为抑制骨吸收药物,可能提高抗骨质疏松疗效。该文将总结老年性骨质疏松症的流行病特点、分子机制、诊断、目前治疗骨质疏松症的药物及联合或序贯用药策略。     

Osteoporosis in men treated with androgen suppression therapy for prostate cancer

Men with advanced or metastatic prostate cancer commonly receive long-term treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy. This prolonged treatment causes a hypogonadal state of chronic testosterone deficiency. Similar to estrogen deficiency in postmenopausal women, testosterone deficiency among these men negatively affects bone metabolism through a complex self-regulating, negative feedback system and subsequent reduction in bone formation. If left undetected or untreated, the risk for osteoporosis rises. Osteoporosis increases the likelihood of fracture, especially of the hips. Researchers are studying the effects of LHRH agonist therapy on osteoporosis and other related conditions to determine whether interventions, such as pharmacologic agents (e.g., bisphosphonates), dietary supplements (e.g., calcium, vitamin D), and exercise, can slow or prevent the process and assist healthcare providers in knowing how to counsel patients. Current recommendations are found in the literature on glucocorticoid-induced and menopausal osteoporosis. Nurses need to stay abreast of current knowledge in this area, as it is expanding rapidly.     

糖尿病性骨质疏松模型雌激素、一氧化氮及转化生长因子β1的变化

背景:糖尿病和卵巢去势是骨质疏松发生的两大主要原因,均会出现一氧化氮和转化生长因子β1的变化。目的:探讨雌激素、一氧化氮、转化生长因子β1在糖尿病性骨质疏松模型中的变化及意义。方法:采用链脲佐菌素诱导制备糖尿病大鼠模型,于造模后4,8,12,16周,进行骨密度检测,并应用放免法检测血清雌激素水平,硝酸还原酶法检测血清一氧化氮水平,ELISA法检测血清转化生长因子β1水平,免疫组织化学法检测骨中转化生长因子β1水平。结果与结论:随着链脲佐菌素诱导时间的延长,糖尿病大鼠股骨骨密度逐渐降低(P<0.05或P<0.01);血清一氧化氮水平逐渐降低(P<0.05或P<0.01);血清转化生长因子β1水平逐渐升高(P<0.01);血清雌激素水平轻度降低,与同时间点正常大鼠比较差异无显著性意义(P>0.05)。免疫组织化学结果显示转化生长因子β1主要表达于成骨细胞的胞浆中,其阳性表达随链脲佐菌素诱导时间的延长逐渐下降(P<0.01)。说明糖尿病大鼠血清一氧化氮水平和骨组织中转化生长因子β1水平的变化导致了骨吸收增加,骨形成减少,使骨密度降低,参与了糖尿病性骨质疏松的发生。     

雌激素影响肌力与骨量间的关系

目的:在研究原发性骨质疏松的发生及防治时,肌力与骨量的关系的影响因素值得关注。本文拟探讨雌激素作为非力学因素影响肌力与骨量之间关系的机制。方法:通过计算机检索肌力与骨量的关系,雌激素对肌力与骨量之间关系的影响的相关文献,结合作者以往的研究工作,论述雌激素对肌力与骨量间关系的影响。结果:肌力决定骨结构和骨量,使骨强度适应运动负荷。雌激素主要通过影响骨应变阈值来调整肌力与骨量之间的关系。雌激素疗法有益于骨组织,部分通过保护肌力实现。结论:雌激素能够影响肌力与骨量的关系,雌激素疗法可能有保护肌力的作用。     

Pharmacy-based bone mass measurement to assess osteoporosis risk

OBJECTIVE: To evaluate elderly women's knowledge of their skeletal status, assess adequacy of calcium intake, determine the prevalence of low bone density, and determine whether peripheral bone density testing led to medical interventions in a group of rural, elderly Wisconsin women recruited in community pharmacies. DESIGN: Recruiting notices were posted in each pharmacy, and eligible women were enrolled in the order in which they volunteered. Each completed a fracture-risk questionnaire. Calcaneal bone density was measured within the following 6 weeks, using peripheral dual-energy X-ray absorptiometry. Mail surveys were used to assess interventions subsequent to the womens' study participation. SETTING: The study was conducted at 5 community pharmacies in rural Wisconsin. RESULTS: Of 133 women, 20% had calcaneal osteoporosis, defined as a T score < or =2.5 (calcaneal bone density <2.5 SDs below the young reference database). Thirty percent of women met National Osteoporosis Foundation (NOF) treatment criteria based on heel bone density and NOF-designated risk factors. Of those meeting treatment criteria, 75% were unaware of their low bone mass. Half of the women received <1200 mg/d of calcium, the recommended dose for osteoporosis prevention. Those who were taking a calcium supplement were much more likely to receive the recommended amount. Women who had discussed bone density test results with their physicians were more likely to receive central dual energy X-ray absorptiometry (DXA) measurements and/or start antiresorptive therapy than women who did not. CONCLUSIONS: Rural, elderly Wisconsin women are at substantial risk for osteoporosis, based on calcaneal bone density, but most are unaware of their risk. Compounding this risk is low calcium intake. Community screening of rural, elderly women by peripheral bone density measurement can lead to medical interventions in such individuals.     

运动干预原发性骨质疏松症：不同运动方式、强度及频率对骨密度的影响

背景：研究证明,运动是骨质疏松症治疗的重要组成部分,适量的运动可以改善骨代谢、提高骨生物力学性能、增加骨密度。目的：从运动对骨代谢的影响、运动对骨生物力学的影响、运动对不同年龄段人群骨密度的影响及不同运动方式、运动强度、运动时间和频率对骨质疏松症的影响等方面,就运动干预对原发性骨质疏松症的研究现状进行探讨。方法：检索2000年1月至2014年6月PubMed数据库及维普中文科技数据库。英文检索词为＂Osteoporosis;Bone Density;Bone Diseases,Metabolic;Exercise Therapy＂;中文检索词为＂骨质疏松症;运动干预;骨密度;骨代谢＂。根据纳入标准保留33篇进一步归纳总结。结果与结论：运动对骨代谢影响的实验提示中等强度运动刺激和雌激素都可以改善骨质疏松的发生程度,对于骨质疏松症的预防、减缓及治疗有积极意义。经过适量运动训练,大鼠去卵巢后体内骨改建的高转换状态可以得到缓解。运动对骨生物力学的影响研究显示,运动和雌激素均能显著提高大鼠股骨骨密度和骨生物力学性能,但运动能够更好地提高骨硬度和增强骨抵抗变形的能力。说明运动训练对骨质疏松大鼠的骨骼和肌肉有良好的刺激效果,肌肉的增大对骨骼质量也有良性的刺激作用。研究结果提示,参加体育活动越早,有可能获得的骨峰值越高,任何时候开始有规律的运动,对维持一定的骨量都有积极的作用。不同时期的运动作用效果不同,儿童期增加骨量,成人期获得骨量并保存骨量,老年期保存骨量减少骨丢失,因此,不同的运动方式和运动强度、频率对骨密度的影响也不同,应根据患者的实际情况,选择合适的运动方式。     

糖尿病性骨质疏松模型雌激素、一氧化氮及转化生长因子131的变化

背景：糖尿病和卵巢去势是骨质疏松发生的两大主要原困,均会出现一氧化氮和转化生长因子β1的变化。目的：探讨雌激素、一氧化氮、转化生长因子B1在糖尿病性骨质疏松模型中的变化及意义。方法：采用链脲佐菌素诱导制备糖尿病大鼠模型,于造模后4,8,12,16周,进行骨密度检测,并应用放免法检测m清雌激素水平,硝酸还原酶法检测血清一氧化氮水平,ELISAi~检测血清转化生长因子D1水平,免疫组织化学法检测骨中转化生长因子B1水平。结果与结论：随着链脲佐菌素诱导时间的延长,糖尿病大鼠股骨骨密度逐渐降低（P〈O.05或P〈0.01）;血清一氧化氮水平逐渐降低（P〈0.05或P〈0.01）;血清转化生长因子β1水平逐渐升高（P〈0.01）：血清雌激素水平轻度降低,与同时间点正常大鼠比较差异无显著性意义（P〉0.05）。免疫组织化学结果显示转化生长因子β1主要表达于成骨细胞的胞浆中,其阳性表达随链脲佐菌素诱导时间的延长逐渐下降（P〈0．01o说明糖尿病大鼠血清一氧化氮水平和骨组织中转化生长因子β1水平的变化导致了骨吸收增加。骨形成减少,使骨密度降低,参与了糖尿病性骨质疏松的发生。     

Diagnose Osteoporose

Background

Osteoporosis is a systemic skeletal disease characterized by decreased bone strength, bone mineral density and bone quality. Fractures caused by low impact trauma are the clinical manifestation of osteoporosis. Major objectives of a fracture risk assessment in osteoporosis are to enable the targeting of interventions to patients with a high risk of fractures and to avoid unnecessary interventions for low-risk patients.

Methods

Persons with specific clinical risk factors and low bone mineral density as well as patients after low impact fractures or atraumatic vertebral fractures have a high risk of fractures. For the therapeutic decision in patients with clinical risk factors, bone mineral density measurements should be included. Major risk factors are old age, smoking, chronic diseases and regular intake of certain medications. Activity and nutrition, in particular adequate protein, calcium and vitamin D intake are preventive measures for healthy subjects as well as for patients with osteoporosis. However, there is a need for osteoporosis-specific medication in the latter. Pain treatment, the prevention of falls, inactivity and immobility are the main targets of the musculoskeletal rehabilitation for patients with an established osteoporosis.     

Pathogenesis of fracture will be important in the research work of osteoporosis

Osteoporosis is characterized by compromised bone strength, and the increased susceptibility to fractures that impair patient's quality of life and increase mortality constitutes a national burden in the aging society. The pathogenesis of osteoporosis has been recently astringent on estrogen deficiency that induces secondary metabolic changes such as calcium imbalance. Thus, the main research issue in osteoporosis has been turning to the mechanical basis of bone fractures. According to the definition of osteoporosis proposed by National Institutes of Health, bone strength reflects the integration of two components: the bone mass (bone mineral density) and bone quality. Of the two, bone mineral density (BMD) is known to be the major determinant of future fracture risk. In contrast, bone quality assessment has not been applied to clinical practice except for the measurement of bone turnover markers. The present paper reviewed the bone quality concepts and discussed the future potential research propositions.     

葛根对睾丸切除骨质疏松模型小鼠骨密度和骨构造的作用

背景:研究证实,葛根不仅能够预防卵巢切除雌激素不足骨质疏松模型小鼠骨密度及骨量的下降,而且能够改善骨微细构造,可用于女性闭经后骨质疏松症的预防与治疗.其对男性骨质疏松的治疗是否具有相似的疗效?目的:课题以更接近应用为目的,观察未经提取的植物药葛根对雄激素不足骨质疏松模型小鼠骨密度和骨构造的影响.方法:8周龄雄性ddY小鼠48只,体质量32～35 g,随机数字表法分为假手术组,模型组,低、中、高剂量葛根组和雌二醇组,每组8只.假手术组暴露睾丸与附睾,切除周围脂肪组织:其余各组小鼠摘除双侧睾丸.术后假手术组、模型组和雌二醇组都给予普通饲料,低、中、高剂量葛根组给予含有5%,10%和20%葛根粉的饲料.雌二醇组1713-雌二醇通过体内小渗透泵自动给药0.03 μg/d.饲料给予均为4.0 g/d.4周后,检测精囊质量,以双能X射线骨密度测定仪检测股骨骨密度,显微CT分析股骨远端干骺端海绵骨微细构造.结果与结论:模型组股骨全体骨密度下降了10.9%,这种下降被低剂量葛根完全抑制,被中剂量葛根抑制进一步加强,但两者差异无显著性意义;高剂量葛根组骨密度较模型组、假手术组分别高出26.1%,12.4%,作用强度与雌二醇相当.低剂量葛根完全抑制了雄激素缺乏导致的股骨骨小梁数目下降以及骨小梁间距增大,中剂量葛根抑制作用更强,但两组之间差异无显著性意义;高剂量葛根组抑制作用最强,能够增加骨量和骨小梁数目达到显著高于假手术组水平.葛根各剂量对精巢无刺激作用.提示葛根在不刺激精囊的条件下,低、中剂量葛根可完全抑制雄激素缺乏所致的骨密度和骨量下降,改善骨构造,高剂量效果更显著,与雌二醇作用相当.     

降脂壮骨中药对食饵性高脂血症大鼠骨组织骨形态发生蛋白2、雌激素受体表达的影响

背景:研究表明活性骨形态发生蛋白2水平的降低可导致严重的类骨质疏松症状,并发现成骨细胞、破骨细胞及骨髓基质细胞上有雌激素受体的存在,认识到雌激素对骨组织具有直接作用.目的:观察降脂壮骨中药对食饵性高脂血症诱发骨质疏松大鼠骨组织骨形态发生蛋白2、雌激素受体表达的影响.方法:健康SD大鼠27只,随机分为3组:正常对照组:上午和下午灌胃生理盐水5 mL/kg;高脂血症诱发骨质疏松模型组:上午灌胃高脂饮食5 mL/kg,下午灌胃生理盐水5 mL/kg;降脂壮骨中药组:上午灌胃高脂饮食5 mL/kg,下午灌胃降脂壮骨中药水提液5 mL/kg.持续干预8周后采用免疫组织化学方法,对其骨组织中骨形态发生蛋白2、雌激素受体的表达水平进行检测,应用原位杂交方法对骨组织中雌激素受体的mRNA水平进行检测.结果与结论:与模型组比较,降脂壮骨中药组骨组织中骨形态发生蛋白2、雌激素受体表达显著增强(P＜0.01),雌激素受体的mRNA表达水平增高.证实降脂壮骨中药能够使食饵性高脂血症诱发骨质疏松大鼠成骨细胞骨形态发生蛋白2、雌激素受体的表达水平增高,起到改善骨质疏松的作用.     

Estrogen Inhibits Bone Resorption by Directly Inducing Apoptosis of the Bone-resorbing Osteoclasts

Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 β-estradiol (E₂) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E₂ also directly induced osteoclast apoptosis in a dose- and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, respectively, completely or partially blocked the effect of E₂ on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct induction of apoptosis of the bone-resorbing osteoclasts by an estrogen receptor– mediated mechanism.     

Bone mineral density and bone turnover in postmenopausal women treated for breast cancer

Chemotherapy and endocrine treatments for breast cancer are believed to increase risk of osteoporosis by causing early menopause in premenopausal women and by further depleting estrogen levels in postmenopausal women. Multivariate analyses were used to evaluate the contributions of 7 predictors (age, body mass index [BMI], family history of osteoporosis, months since menopause, past use of chemotherapy, and current use of tamoxifen or aromatase inhibitors) in explaining variability in bone mineral density (BMD) at the hip and the spine and bone turnover in 249 postmenopausal women who are breast cancer survivors. This report was an analysis of baseline data from a federally funded (1 R01 NR07743-01A1) intervention study on osteoporosis prevention. Mean age of the women was 58.5 years, and average BMI was 26.7 kg/m; 98% were white. All had measurable bone loss, 167 had chemotherapy, 76 were on tamoxifen, and 21 were on aromatase inhibitors. Women with higher BMI had higher BMD at the hip (P < .001) and the spine (P = .004). Women on tamoxifen had lower measures of bone formation (Alkphase B) (P < .001), suggesting less bone turnover, and higher BMD at the hip (P = .035). There was a trend for women who had received chemotherapy to have lower BMD at the spine (P = .06). The implications of these findings are discussed in the article.     

Osteoporosis treatment by gynecologist

Postmenopausal bone loss is accelerated since women experience menstrual irregularity. Postmenopausal women lose their bone mineral density by 20 to 25% during 10 years after menopause, therefore early detection of risks for postmenopausal osteoporosis is mandatory for prevention of the disease. Because estrogen deficiency is the primary cause of postmenopausal bone loss, hormone replacement therapy can be a reasonable choice for the first treatment of osteoporosis. However, to those who have contraindications against estrogen or who complain severe estrogen-related symptoms, other medication using SERM and bisphosphonate should be considered.     

Postmenopausal osteoporosis

Osteoporosis is a major public health problem, particularly for the postmenopausal woman. With the withdrawal of estrogen at menopause, bone resorption begins to exceed formation in remodeling cycles and bone mass is inexorably lost. Clearly, preventing postmenopausal osteoporosis is the aim of management. Individuals with risk factors for developing this condition should have noninvasive bone density determination and should be considered for preventive regimens. Therapeutic options for prevention include calcium, estrogen, and exercise. Once osteoporosis is established, therapeutic options may include those listed previously as well as fluoride and other modalities currently under investigation.