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.     

Ethnic variation in risk for osteoporosis among women: a review of biological and behavioral factors

Most studies of risk factors for osteoporosis and nontraumatic fracture involve white women, although more research is being geared toward bone health among various ethnic groups. The purpose of this review is to provide an overview of health disparity in osteoporosis, including assessment of bone mineral density (BMD), bone health screening, lifestyle risk factors, and treatment involving white, black, Hispanic, Asian, and Native American women. This review summarizes evidence that white, Asian, Hispanic, and Native American women are more at risk for osteoporosis than black women. These conclusions are supported by the disparity in BMD between white and black women, although the reason for this biological difference is not well characterized. Additional research is needed to determine if there is a significant difference in BMD among Hispanic, Asian, and Native American women independent of body weight and size. Similarly, there is also disparity in fracture rates, with the causes presumed to be multifactorial. Calcium intake is lower than recommended in all females at all ages; however, it is much lower in black and Native American women and highest in white and Hispanic women. Black women also have a lower vitamin D status than white women, with mean vitamin D status of Hispanic American women lying between that of black and white women. Similarly, although white women are more active than black and Hispanic women at all ages, data are lacking about physical activity habits of women of other ethnic backgrounds and how this impacts bone health. Finally, screening protocols for women of various ethnicities and effectiveness of treatments are not well established and remain a priority in women's health.     

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.     

上海市两区618例老年人骨密度及相关因素

[目的]研究影响上海市两区(地处中心城区)老年人骨密度的相关因素。[方法]采用经培训专职人员一对一方式对户籍为上海市两区的618名60岁及以上老年人进行问卷调查,应用骨密度仪对受试者足踝部进行骨密度(BMD)测定。对测得结果进行多元逐步回归分析。[结果]老年人年龄、性别、饮碳酸饮料、户外运动、服用钙片、既往骨折史与骨密度高低具有相关性(P0.05)。老年女性经常饮用碳酸饮料,骨密度下降明显(P0.05);老年男性经常饮酒,骨密度下降明显(P0.05)。[结论]该两区老年人具有较明显的地域生活习性,在注重年龄、性别、既往有骨折史等骨质疏松危险因素预防的同时,应鼓励老年人多进行户外运动、定期服用钙片等。老年女性应避免或少饮用碳酸饮料,老年男性应不饮酒或少饮酒。     

Osteoporosis for the home care physician. Part 1: etiology and current diagnostic strategies

Osteoporosis affects over 20 million individuals in North America and is responsible for over 1.5 million fractures in the US. Although most cases of osteoporosis are primary, in 20% of older women and 40% of older men presenting with vertebral fractures, a secondary cause can be identified. The WHO based the diagnosis of postmenopausal osteoporosis on the presence of BMD T-score that is 2.5 standard deviations or greater below the mean for young women. The International Society of Clinical Densitometry defined male osteoporosis as BMD T-score of 2.5 or greater below the mean for young men. BMD assessment at the hip and spine by DXA is the standard procedure to assess bone density. Laboratory testing in patients with low BMD is performed to exclude other conditions that could cause low BMD such as multiple myeloma, endocrinopathies and osteomalacia. Bone turnover marker levels currently do not predict bone mass or fracture risk and are only weakly associated with changes in bone mass. Subsequently, they are of limited use in the clinical evaluation of bone density changes.     

Exercise and physical activities for the prevention of osteoporotic fractures: a review of the evidence

According that osteoporosis is the common condition in an aging society such as in Japan, much progress has been made in understanding the treatment and prevention of osteoporosis. Among potential risk factors, exercise and physical activities have been recognized as lifestyle factors that might influence the risk of osteoporosis and osteoporotic fractures. To assess the relationship between exercises including physical activities and the risk for low bone mass and osteoporosis-related fractures, a literature search over past 13 years was conducted. Accumulating evidence indicates that exercises decrease the risk for hip fractures among middle aged and older men and women. Exercises also help to maintain muscle strength, muscle volume, balance, and joint flexibility, which might prevent falls and fall-related fractures. One randomized controlled trial showed back-stretching exercise reduced the risk for vertebral fractures. The literature search also indicates that high-impact and/or weight-bearing exercise might increase the bone density in the elderly and the peak bone mass among young women, while there is no association between moderate or lower-impact exercise and bone mineral density. Future research should be required to evaluate the types and quantity of physical activity needed for the prevention of osteoporosis.     

Progestogen-only contraception and bone mineral density: a systematic review

Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.     

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.     

Incremental Predictive Value of Sarcopenia for Incident Fracture in an Elderly Chinese Cohort: Results From the Osteoporotic Fractures in Men (MrOs) Study

ObjectivesWe examined whether sarcopenia is predictive of incident fractures among older men, whether the inclusion of sarcopenia in models adds any incremental value to bone mineral density (BMD), and whether sarcopenia is associated with a higher risk of fractures in elderly with osteoporosis.MethodsA cohort of 2000 community-dwelling men aged ≥65 years were examined for which detailed information regarding demographics, socioeconomic, medical history, clinical, and lifestyle factors were documented. Body composition and BMD were measured using dual energy X-ray absorptiometry. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) algorithm. Incident fractures were documented during the follow-up period from 2001 to 2013, and related to sarcopenia and its component measures using Cox proportional hazard regressions. The contribution of sarcopenia for predicting fracture risk was evaluated by receiver operating characteristic analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsDuring an average of 11.3 years of follow-up, 226 (11.3%) men sustained at least 1 incident fracture, making the incidence of fractures 1200.6/100,000 person-years. After multivariate adjustments, sarcopenia was associated with increased fracture risk (hazard ratio [HR], 1.87, 95% confidence interval [CI], 1.26–2.79) independent of BMD and other clinical risk factors. The addition of sarcopenia did not significantly increase area under curve or IDI but significantly improved the predictive ability on fracture risk over BMD and other clinical risk factors by 5.12% (P < .05) using the NRI approach. In addition, the combination of osteoporosis and sarcopenia (sarco-osteoporosis) resulted in a significantly increased risk of fractures (HR, 3.49, 95% CI, 1.76–6.90) compared with those with normal BMD and without sarcopenia.ConclusionsThis study confirms that sarcopenia is a predictor of fracture risk in this elderly men cohort, establishes that sarcopenia provides incremental predictive value for fractures over the integration of BMD and other clinical risk factors, and suggests that the combination of osteoporosis and sarcopenia could identify a subgroup with a particularly high fracture risk.     

Patient assessment in the diagnosis, prevention, and treatment of osteoporosis.

Assessment of the patient with osteoporosis includes history and physical examination, laboratory testing, and imaging studies. Information gathered during this assessment assists clinicians in targeting strategies to prevent fractures. The medical history should contain items such as personal and family history of fractures, lifestyle, intake of substances such as vitamin D, calcium, corticosteroids, and other medications. The physical examination can reveal relevant information such as height loss and risk of falls. Bone mineral density (BMD), most commonly determined by dual-energy x-ray absorptiometry, best predicts fracture risk in patients without previous fracture. BMD testing is most efficient in women over 65 years old but is also helpful for men and women with risk factors. Serial BMD tests can identify individuals losing bone mass, but clinicians should be aware of what constitutes a significant change. Laboratory testing can detect other risk factors and can provide clues to etiology. Selection of laboratory tests should be individualized, as there is no consensus regarding which tests are optimal. Biochemical markers of bone turnover have a potential role in fracture risk assessment and in gauging response to therapy, but are not widely used at present. Clinicians should be aware of problems with vitamin D measurement, including seasonal variation, variability among laboratories, and the desirable therapeutic range. Careful assessment of the osteoporotic patient is essential in developing a comprehensive plan that reduces fracture risk and improves quality of life.     

Zinc intakes and plasma concentrations in men with osteoporosis: the Rancho Bernardo Study

BACKGROUND: Low zinc intakes and reduced blood zinc concentrations have been reported to be associated with osteoporosis in women. OBJECTIVE: The objective was to examine the independent association between dietary zinc and plasma zinc and the association of each with bone mineral density (BMD) and 4-y bone loss in community-dwelling older men. DESIGN: Of the original Rancho Bernardo Study subjects, 396 men (age: 45-92 y) completed BMD measurements at baseline in 1988-1992 and 4 y later. Osteoporosis was defined as a BMD > or = 2.5 SDs below the mean for young women (a T-score < or = -2.5). At baseline, dietary intake data were collected by using a standard food-frequency questionnaire, and plasma zinc concentrations were measured by using inductively coupled plasma spectroscopy. RESULTS: The mean dietary zinc intake was 11.2 mg, and the mean plasma zinc concentration was 12.7 micromol/L. Plasma zinc was correlated with total zinc intake (diet plus supplements). Dietary zinc intake and plasma zinc concentrations were lower in men with osteoporosis at the hip and spine than in men without osteoporosis at those locations. BMDs for the hip, spine, and distal wrist were significantly lower in men in the lowest plasma zinc quartile (<11.3 micromol/L) than in men with higher plasma zinc concentrations. The association between plasma zinc and BMD was cross-sectional, longitudinal, and independent of age or body mass index. However, plasma zinc did not predict bone loss during the 4-y interval. CONCLUSION: Dietary zinc intake and plasma zinc each have a positive association with BMD in men.     

Risk factors for osteoporosis: A review

Skeletal fragility and falls are the 2 most potent factors leading to osteoporotic fractures. The aim of this article is to review factors associated with women's risk of developing skeletal fragility and subsequent osteoporosis. Many factors have been implicated, but the evidence for some is unsubstantial. Low premenopausal bone mineral density (BMD), a decrease in BMD, and an increase in bone fragility -- which occur as a result of both aging and the menopause -- are major determinants of subsequent risk for osteoporotic fracture. In addition, low body mass index (BMI), low calcium intake, low physical activity, and smoking can affect BMD. The relative importance of the effects these physical and lifestyle factors have on BMD in midlife women is not fully established. The impact of gynecologic history (parity, lactation, oral contraceptive use, age of menarche) on BMD is uncertain.     

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。     

Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis

Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment.     

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。     

Effect of alendronate on bone mineral density in Puerto Rican males with osteoporosis

Osteoporosis in men was not recognized as a major health problem until recently, and increased research in this area resulted in the approval of alendronate for the treatment of osteoporosis in men at the beginning of this decade. Low bone mineral density (BMD) has been demonstrated to be a strong predictor of fracture in men as it is in women. The causes of osteoporosis in men are variable and can be classified as primary or secondary. The aim of these report is to present the response of BMD in 10 Puerto Rican men with secondary causes of osteoporosis treated with alendronate. A significant increase of BMD in spine, total hip, trochanter and intertrochanteric regions were noted. A non-significant increase in femoral neck was observed.     

Dairy intakes affect bone density in the elderly

BACKGROUND: Race and sex differences in the effect of diet on bone mineral density (BMD) at the hip in the elderly are unknown. OBJECTIVES: This study related cross-sectional nutrient and dairy product consumption to hip BMD in white and black men and women aged >60 y and evaluated the influence of nutrient and dairy product consumption on changes in BMD in a white cohort participating in a calcium, vitamin D, or placebo trial. DESIGN: The Health Habits and History Questionnaire was used in 289 white women and 116 white men who participated in the trial and in 265 black women and 75 black men to predict total hip and femoral neck BMD or changes in BMD. RESULTS: Blacks had higher calcium intakes than did whites (700 and 654 mg/d, respectively; P = 0.0094), and men had higher calcium intakes than did women (735 and 655 mg/d, respectively; P = 0.0007). For men, the correlation between total hip BMD and dairy calcium intake after adjustment for age, race, and weight was 0.23 (P < 0.005); this relation was not significant in women (r = 0.02, P = 0.12). Similar results were found for femoral neck BMD. In the longitudinal study, calcium supplementation reduced bone loss from the total hip and femoral neck in those who consumed <1.5 servings of dairy products/d and were <72 y old. CONCLUSIONS: Cross-sectional results indicated that higher dairy product consumption is associated with greater hip BMD in men, but not in women. Calcium supplementation protected both men and women from bone loss in the longitudinal study of whites.     

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.     

Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women

BACKGROUND: Osteoporosis and related fractures will be growing public health problems as the population ages. It is therefore of great importance to identify modifiable risk factors. OBJECTIVE: We investigated associations between dietary components contributing to an alkaline environment (dietary potassium, magnesium, and fruit and vegetables) and bone mineral density (BMD) in elderly subjects. DESIGN: Dietary intake measures were associated with both cross-sectional (baseline) and 4-y longitudinal change in BMD among surviving members of the original cohort of the Framingham Heart Study. Dietary and supplement intakes were assessed by food-frequency questionnaire, and BMD was measured at 3 hip sites and 1 forearm site. RESULTS: Greater potassium intake was significantly associated with greater BMD at all 4 sites for men and at 3 sites for women (P < 0.05). Magnesium intake was associated with greater BMD at one hip site for both men and women and in the forearm for men. Fruit and vegetable intake was associated with BMD at 3 sites for men and 2 for women. Greater intakes of potassium and magnesium were also each associated with less decline in BMD at 2 hip sites, and greater fruit and vegetable intake was associated with less decline at 1 hip site, in men. There were no significant associations between baseline diet and subsequent bone loss in women. CONCLUSION: These results support the hypothesis that alkaline-producing dietary components, specifically, potassium, magnesium, and fruit and vegetables, contribute to maintenance of BMD.     

Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women

BACKGROUND: Vitamin K has been associated with bone mineral density (BMD) and risk of hip fracture. The apolipoprotein (apo) E4 allele (APOE*E4) has been associated with bone fracture through a putative effect on vitamin K transport in blood. OBJECTIVE: The objective was to determine the associations between vitamin K intake, apo E genotype, BMD, and hip fracture in a population-based cohort of elderly men and women. DESIGN: Dietary vitamin K intake was assessed with a food-frequency questionnaire in 335 men and 553 women (average age: 75.2 y) participating in the Framingham Heart Study in 1988-1989. Incidence of hip fractures was recorded from 1988 to 1995. BMD at the hip, spine, and arm was assessed on 2 separate occasions (1988-1989 and 1992-1993). Comparisons between apo E genotype and BMD were made relative to E4 allele status (at least 1 epsilon4 allele compared with no epsilon4 allele). RESULTS: Individuals in the highest quartile of vitamin K intake (median: 254 microg/d) had a significantly lower fully adjusted relative risk (0.35; 95% CI: 0. 13, 0.94) of hip fracture than did those in the lowest quartile of intake (median: 56 microg/d). There were no associations between vitamin K intake and BMD in either men or women. No association was found between the E4 allele and BMD, and there were no significant interactions between the E4 allele and phylloquinone intake and BMD or hip fracture. CONCLUSIONS: Low vitamin K intakes were associated with an increased incidence of hip fractures in this cohort of elderly men and women. Neither low vitamin K intake nor E4 allele status was associated with low BMD.