Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action?

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.     

Present condition and prospect in clinical medicine of osteoporosis

The criteria for initiating pharmacotherapy to prevent fragility fractures should be provided separately from the criteria for diagnosis of osteoporosis. In Japan, low BMD (bone mineral density), prevalent fracture, and age are established as fracture risk factors. A meta-analysis conducted by the WHO assured that excessive drinking, current smoking, and family history of hip fracture are fracture risk factors. Pharmacotherapy should be initiated with the consideration of the above risk factors. Recent large scale of RCT demonstrated that bisphosphonates as well as raloxifene are top grade of drugs which prevent fragility fracture. As for secondary osteoporosis, accumulating evidence is available about increased fracture threshold in glucocorticoid- and diabetes mellitus-induced osteoporosis. In osteoporotic patients, atherosclerosis often coexists. Multiple vertebral fractures follwed by kyphosis often causes functional disorders of the digestive and respiratory systems. It is, therefore, required to perform tailor-made medicine, based on the possibility that concomitant diseases exist in osteoporotic patients.     

Guidelines for the diagnosis of osteoporosis by densitometric methods

BACKGROUND: Osteoporosis is a major health hazard for postmenopausal women and elderly people. Local, national, and international organizations developed clinical practice guidelines for the diagnosis and management of osteoporosis and the prevention of osteoporotic fractures. Low bone mineral density (BMD) is the most important risk factor for fragility fractures. Bone densitometry is the best method to measure BMD in an individual. Many risk factors contribute to the development of osteoporosis and increase the fracture risk independently from BMD. Guidelines must be comprehensive, factual, simple to implement, and should provide the clinician, patients, governments, and payers with the best evidence available. OBJECTIVES: The objectives of this article were to review national and international guidelines to establish a congruent set of parameters that may aid the clinician in the decision-making process for the diagnosis of osteoporosis. DATA SOURCES: An online search of several databases provided 18 guidelines for this review. Comparison among the guidelines was made on 10 different aspects: format, focus, significance of hip and vertebral body fractures, primary diagnostic considerations, BMD measurement technology, interpretation, reporting and follow-up, equipment reliability and quality control, risk factors considered, and methodologic quality of the guidelines. Tables were created for easier comparison on the aspects covered and supported by each guideline. RESULTS: None of the guidelines reviewed fulfills all the requirements of good clinical practice guidelines. CONCLUSIONS: Further works should finally provide all those interested with a more complete and thorough set of guidelines based on the best evidence available.     

Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis

Osteoporosis is defined as a progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The clinical relevance of osteoporosis derives from the fractures that it produces. More than one-third of the adult women will suffer one or more osteoporotic fractures in their lifetime. The lifetime risk in men is approximately one-half that in women. The decrease of the bone mineral density is the most important cause of risk fracture. Among other factors, Ca(2+) and vitamin D deficiencies are important risk factors for a decrease in bone mineral density, consequently inducing osteoporosis. The high prevalence of vitamin D deficiency in healthy elderly people living mainly in southern European countries increase the risk of osteoporotic fractures in these populations above those anticipated for the general elderly population of the European community. In addition, the ageing of the European population will double the number of osteoporotic fractures over the next 50 years, unless adequate preventative measures are undertaken. The efficacy and safety of Ca(2+) and vitamin D supplements at preventing bone loss and reducing the risk of hip and other fractures have been assessed in different clinical trials, which are extensively discussed in this review.     

Osteoporosis in older men

Historically, the focus in osteoporosis has been on postmenopausal women. In the past few years, information about osteoporosis in other populations, including men, has begun to emerge. Although less common in older men, osteoporosis nonetheless represents a major health concern. Approximately 30% of hip fractures worldwide occur in men, resulting in significant mortality and loss of independence. The incidence of osteoporotic fractures in men is increasing. The reason for this is unclear, but improvement in longevity and better management of other chronic diseases most likely play a role. Two recent studies have addressed the question of fracture risk in men past middle age and have estimated that men > 50 years of age have a 19% to 25% lifelong risk of osteoporotic fracture. Mortality is higher following hip fracture and pain is more intense in men than in women following severe vertebral fracture.     

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.     

Risedronate prevents hip fractures,but who should get therapy?

The Hip Intervention Program (HIP) trial establishes that risedronate (Actonel) prevents hip fracture in elderly women with osteoporosis. However, the drug had no statistically significant effect on hip fracture risk in elderly women in whom bone density status was not known. Patients should be selected for bisphosphonate therapy on the basis of low bone density. A history of vertebral fractures increases the risk for hip fractures.     

Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.     

骨质疏松症患者激素替代治疗的临床证据

目的评估绝经后骨质疏松症激素替代治疗的有效性。方法计算机检索Cochrane Library（2008年第4期）、MEDLINE（1978～2008）、Clinical Evidence中有关的系统评价和Meta分析。检索词为postmenopausal（post-menopausal）osteoporosis、therapy、vertebral fracture、hormone replacement therapy、randomized controlled trial、meta-analysis、female、human。结果在Cochrane Library共检索到4篇研究方案和9篇系统评价全文,在MEDLINE检索到1篇Meta分析。结果表明,采用激素替代治疗（HRT）后,骨皮质和骨松质的骨密度（BMD）均明显增加,椎体和非椎体骨折的发生率有下降趋势。结论激素替代治疗能增加骨密度,预防骨质疏松性骨折的发生。但患者在获得骨密度增加的同时其他疾病和不良事件风险增加,因此在进行激素替代治疗前应从多方面权衡得失。     

Management of Osteoporosis and Spinal Fractures: Contemporary Guidelines and Evolving Paradigms

Physicians involved in treating spine fractures secondary to osteopenia and osteoporosis should know the pathogenesis and current guidelines on managing the underlying diminished bone mineral density, as worldwide fracture prevention campaigns are trailing behind in meeting their goals. This is a narrative review exploring the various imaging and laboratory tests used to diagnose osteoporotic fractures and a comprehensive compilation of contemporary medical and surgical management. We have incorporated salient recommendations from the Endocrine Society, the American Association of Clinical Endocrinology (AACE), and the American Society for Bone and Mineral Research (ASBMR). The use of modern scoring systems such as Fracture Risk Assessment Tool (FRAX®) for evaluating fracture risk in osteoporosis with a 10-year probability of hip fracture and major fractures in the spine, forearm, hip, or shoulder is highlighted. This osteoporosis risk assessment tool can be easily incorporated into the preoperative bone health optimization strategies, especially before elective spine surgery in osteoporotic patients. The role of primary surgical intervention for vertebral compression fracture and secondary fracture prevention with pharmacological therapy is described, with randomized clinical trial-based wisdom on its timing and dosage, drug holiday, adverse effects, and relevant evidence-based literature. We also aim to present an evidence-based clinical management algorithm for treating osteoporotic vertebral body compression fractures, tumor-induced osteoporosis, or hardware stabilization in elderly trauma patients in the setting of their impaired bone health. The recent guidelines and recommendations on surgical intervention by various medical societies are covered, along with outcome studies that reveal the efficacy of cement augmentation of vertebral compression fractures via vertebroplasty and balloon kyphoplasty versus conservative medical management in the elderly population.     

Hip fracture prevention. Drug therapies and lifestyle modifications that can reduce risk

The annual number of hip fractures sustained worldwide is expected to increase dramatically as the population ages. Adequate calcium and vitamin D intake and exercise are fundamental to any program for bone loss prevention or osteoporosis treatment. Fall prevention programs, weight-bearing and resistance exercise, hip protector use, and calcium and vitamin D supplementation can reduce hip fracture risk. Among the available antiosteoporosis agents, the bisphosphonates risedronate and alendronate have produced the greatest reductions in hip fracture risk in postmenopausal women. Nasal calcitonin and raloxifene have not demonstrated significant reductions in nonvertebral or hip fracture risk. The role of parathyroid hormone (1-34) in the treatment of hip fractures remains uncertain until more experience is gained about its use and studies with sufficient statistical power are performed. Data indicate that bisphosphonates consistently reduce hip fracture risk in patients with osteoporosis, especially those with an existing vertebral fracture. In addition to pharmacologic intervention, adequate nonpharmacologic preventive strategies should be included to ensure maximal reduction in risk of hip fracture.     

Osteoporosis diagnosis and screening

Osteoporosis and osteoporotic fracture are major causes of morbidity and mortality in the United States and worldwide. Nearly half of all women and one quarter of men >50 years of age will experience an osteoporosis-related fracture during their lifetime. The diagnosis of osteoporosis in postmenopausal women and older men can be made definitively by comparing bone mineral density (BMD) measurements from dual-energy x-ray absorptiometry (DXA) to mean peak bone mass in young adults. Efforts to increase access to DXA and improve the sensitivity and specificity of osteoporosis risk assessment instruments may help ensure that individuals with osteoporosis are diagnosed early. The early identification of individuals with low BMD and/or clinical risk factors, accurate diagnosis of osteoporosis and osteopenia, and initiation of appropriate treatment are crucial to reducing the incidence of vertebral and nonvertebral fractures. The World Health Organization is moving toward absolute risk assessment and this may help to better identify patients for screening and treatment in the future.     

Quantitative bone ultrasound at phalanges and calcaneus in osteoporotic postmenopausal women: influence of age and measurement site

Phalangeal and calcaneal quantitative ultrasound (QUS) measurements were tested in a postmenopausal osteoporotic population of a wide age range to assess their ability to identify subjects with vertebral fractures in a population of postmenopausal women with osteoporosis. A group of 127 osteoporotic women aged from 50 to 85 y, who had been postmenopausal for at least 5 y, were enrolled. All subjects underwent phalangeal and calcaneal QUS measurements, femoral neck and lumbar spine dual energy X-ray absorptiometry (DXA) measurements and lateral thoracic and lumbar spine radiography. Osteoporosis was defined on the basis of femoral neck or lumbar spine bone mineral density (BMD) T-score lower than -2.5 SD or of the presence of one or more vertebral atraumatic fractures, independently of BMD values. Fifty-two women had one or more vertebral fractures, while the remaining 75 had no evidence of previous fracture. Both QUS techniques were able to discriminate between fractured and nonfractured subjects in the whole group (p < 0.05). When patients aged <70 y (n = 43) and patients aged > or = 70 y (n = 84) were considered separately, phalangeal QUS and lumbar spine BMD were able to discriminate vertebral fractures in the younger group (p < 0.05), whereas calcaneal QUS was able to discriminate vertebral fractures in the older one (p < 0.05). The results of this study raise an issue of the optimal use of different QUS techniques and different skeletal sites in the management of osteoporosis in early or late postmenopausal life.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

甲状旁腺激素预防和治疗绝经后骨质疏松症疗效的系统评价

目的系统评价甲状旁腺激素（PTH）预防和治疗绝经后骨质疏松症的疗效和安全性。方法计算机检索MEDLINE（1966～2008．3）、EMBASE（1974—2008．3）、Cochrane图书馆临床试验资料库（2008年第1期）、Current Controlled Trials、The National Reseach Register、中国生物医学文献数据库（1983—2008．3）、中国期刊全文数据库（1994～2008．3），并手工检索相关领域其它杂志。检索不受语种限制，时间截至2008年3月。纳入以患原发性质疏松症或骨量减少的绝经后女性为研究对象、比较甲状旁腺激素与其它疗法疗效的随机对照试验，评价纳入研究的质量，并用RevMan4．2．10软件进行Meta分析。结果共纳入12个随机对照试验，包括5550例患者。Meta分析结果显示：PTH单用或与其它药物联用与对照组比较，减少椎体骨折风险达66％[RR=0．34，95％CI（0．26，0．45），P〈0．00001]；增加腰椎[SMD=0．41，95％CI（0．19，O．63），P=0．0003]和股骨颈[SMD=0．19，95％CI（0．10，0．28），P〈0．0001]的骨密度优于对照组。PTH发生副作用导致的退出和失访多于对照组[Peto—OR=1．69，95% CI（1．39，2．05），P〈0．00001]。结论PTH预防和治疗绝经后骨质疏松症疗效肯定，能提高腰椎及股骨颈的骨密度，降低椎体骨折的风险。PFH对绝经后骨质疏松症的疗效优于阿伦磷酸盐，但不宜和阿伦磷酸盐联合使用，骨量严重低下和有骨质疏松性骨折的绝经后女性是PTH较适合的人群。     

A neuromuscular test battery for osteoporotic women: a pilot study

OBJECTIVE: To examine the efficacy of a short neuromuscular test battery in elderly women suffering from osteoporosis in accordance with the World Health Organization criteria, with and without a history of fractures. Reduced bone mass and a high likelihood of falling increase the risk of osteoporotic fractures. There is a need for neuromuscular tests to identify individuals at risk for falls and fractures. DESIGN: The women were assessed twice. Forty-two women, with a mean age of 70.0 +/- 5.1 (SD) yr, completed the first assessment. The number of postmenopausal fractures and the women's history with regard to agility and falls were assessed. The women performed neuromuscular tests (one-leg stance, tandem walk, and body sway); bone mineral density of the spine and femoral neck were measured. For the follow-up assessment, 13.2 +/- 1.3 mo later, 39 women were studied. The same outcome measurements were obtained at both evaluations. RESULTS: During the observation period, five women fell once and one woman fell twice; there were only two vertebral fractures and no nonvertebral fracture. Neuromuscular performance did not change during this observation period. The median changes in bone mineral density between the two assessments were clinically not relevant. A comparison between patients suffering from established osteoporosis and osteoporotic patients without a history of postmenopausal fractures showed that both groups of patients did not differ with respect to age, neuromuscular performance, bone mineral density, and fear of falling. CONCLUSION: This neuromuscular test battery is a feasible and practical tool because it is brief and economical to perform. However, its efficacy as a predictor of fractures must be tested in additional studies with a long-term follow-up and a larger group of subjects.     

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. Methods: In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS: In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS: s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.     

DXA, QUS, and radiogram

In this article, an outline of dual energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS), and radiogram, and their characteristics, problems, and assessment of osteoporosis in the elderly were reviewed. It is well known that both DXA and QUS are available to risk assessment of fractures. However, because lumbar bone mineral density (BMD) is overestimated in the elderly complicated with fracture, deformity, and osteosclerotic change in the lumbar vertebra (e), some cases are unsuitable to measurement of BMD with lumbar DXA. To define vertebral fracture, visual semiquantitative and morphometric methods are used. In addition, differential diagnosis of osteoporotic vertebral fractures is necessary. Thus, to establish an exact diagnosis of osteoporosis in the elderly, it is important to understand some problems associated with the elderly.     

FRAX软件评估中老年骨量减少患者骨折风险的价值

目的应用FRAX软件评估中老年患者骨折风险,为临床干预骨质疏松提供指导。方法对纳入的395例人群采用FRAX骨折风险评估表,登记有关临床资料,并测定L2~L4和髋部骨密度,分析骨折的相关风险因素。结果①395例调查者中男女比例为1.23∶1;女性患者腰椎骨密度明显低于男性患者(P0.01),骨折风险明显大于男性患者(P0.01)。②不同年龄段男性骨折风险不同,主要部位脆性骨折风险以50~59岁年龄段最高(P0.01),髋部脆性骨折风险以60~69岁年龄段最高(P0.05);不同年龄段女性骨折风险不同,主要部位脆性骨折风险以60~69岁年龄段最高(P0.05),髋部脆性骨折风险以60~69岁年龄段最高(P0.05)③主要部位脆性骨折风险与腰椎及髋部骨密度均呈线性负相关(r=-0.498,r=-0.517),与男性患者年龄呈线性负相关(r=-0.608)。④髋部脆性骨折风险与腰椎骨密度、髋部骨密度及年龄呈线性负相关(r=-0.469,r=-0.613,r=-0.033),与女性患者年龄呈线性正相关(r=0.124)。⑤男性、女性主要部位和髋关节脆性骨折风险值识别骨量减少的受试者工作特征(ROC)曲线下面积分别在0.625、0.838和0.821和0.890(P0.05)。结论 FRAX可以为临床评估骨折风险提供帮助,对骨质疏松的干预提供帮助。     

Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.