Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

BACKGROUND: Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. METHODS: We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. RESULTS: At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. CONCLUSIONS: In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.

Bone Mineral Density, Anthropometric Indices, and the Prevalence of Osteoporosis in Northern (Beijing) Chinese and Southern (Hong Kong) Chinese Women--The Largest Comparative Study to Date.

This study was designed to compare the bone mineral density (BMD) and the prevalence of osteoporosis in community-dwelling women (aged 50-89) living in Northern (Beijing) and Southern (Hong Kong) China. Six thousand ninety-nine ambulatory Chinese women living in Hong Kong and 6302 mainland Chinese women living in Beijing were recruited for the study. The BMD was found to be 2.2% higher at the lumbar spine, 8.4% higher at the total hip, and 7.2% higher at the femoral neck in Beijing women than those in Hong Kong women. However, after adjustment for age, weight, and height, this trend was reversed so that the adjusted BMD at the lumbar spine, total hip, and femoral neck was 4.8%, 2.7%, and 1.4% higher in Hong Kong Chinese women than Beijing Chinese women, respectively. Body weight accounted for 13.3%, 14.6%, and 10.6% of the difference in BMD of lumbar spine, total hip, and femoral neck between the 2 populations. The prevalence of osteoporosis in Hong Kong women (24.9%) was found to be higher than that in Beijing women (20.3%). We conclude that osteoporosis is a major health problem in Chinese women, and in comparing BMD between subjects of the same ethnicity, body weight must be taken into account.

International and ethnic variability of falls in older men.

AIMS: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. METHODS: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. RESULTS: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. CONCLUSIONS: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.

Visual functioning and quality of life among the older people in Hong Kong.

OBJECTIVES: This study aimed to examine the association of visual functioning and health-related quality of life (HRQOL) among the older community in Hong Kong. DESIGN: This study used the baseline examination of a cohort study MrOs and MsOs (a large study for osteoporosis in men and women). SETTING: This study was set in the Hong Kong community. PARTICIPANTS: A total of 4000 ambulatory community-dwelling Chinese men and women aged 65 years or above participated in this study. MEASUREMENTS: Health-related quality of life was assessed by Medical Outcomes Study Short Form-12 (SF-12), with physical component summary (PCS) and mental component summary (MCS) scores. Demographics, medical history, mental status, and quality of life were obtained from face-to-face interviews, using standard structured questionnaire. Visual functions (i.e., binocular visual acuity, contrast sensitivity, and stereopsis) were assessed by different visual tests after refraction corrections. Different visual functions were tested simultaneously in multiple ordinal logistic regression models. RESULTS: Better binocular visual acuity, contrast sensitivity, and stereopsis were associated with higher PCS. Visual acuity and contrast sensitivity was associated with PCS after adjustment of different visual functions and sex, age, education level, cognitive status, and history of diabetes in multivariate analysis, (OR = 0.73, 95% CI = 0.54 0.98) for low vision (≤6/24) compared with ≥6/9 in visual acuity and (OR = 1.34, 95% CI = 1.09 1.64) for contrast sensitivity row b 5-8 (best) compared with 0-1 (worst). MCS was only associated with visual acuity and contrast sensitivity, but no association was found after adjustment. CONCLUSION: Apparent association was found between visual functions and HRQOL among older community in Hong Kong. In addition to visual acuity, contrast sensitivity is also important, so eye care should also cover.

Industry funding of patient and health consumer organisations: systematic review with meta-analysis.

OBJECTIVE: To investigate pharmaceutical or medical device industry funding of patient groups. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Ovid Medline, Embase, Web of Science, Scopus, and Google Scholar from inception to January 2018; reference lists of eligible studies and experts in the field. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies including cross sectional, cohort, case-control, interrupted time series, and before-after studies of patient groups reporting at least one of the following outcomes: prevalence of industry funding; proportion of industry funded patient groups that disclosed information about this funding; and association between industry funding and organisational positions on health and policy issues. Studies were included irrespective of language or publication type. REVIEW METHODS: Reviewers carried out duplicate independent data extraction and assessment of study quality. An amended version of the checklist for prevalence studies developed by the Joanna Briggs Institute was used to assess study quality. A DerSimonian-Laird estimate of single proportions with Freeman-Tukey arcsine transformation was used for meta-analyses of prevalence. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of the evidence for each outcome. RESULTS: 26 cross sectional studies met the inclusion criteria. Of these, 15 studies estimated the prevalence of industry funding, which ranged from 20% (12/61) to 83% (86/104). Among patient organisations that received industry funding, 27% (175/642; 95% confidence interval 24% to 31%) disclosed this information on their websites. In submissions to consultations, two studies showed very different disclosure rates (0% and 91%), which appeared to reflect differences in the relevant government agency's disclosure requirements. Prevalence estimates of organisational policies that govern corporate sponsorship ranged from 2% (2/125) to 64% (175/274). Four studies analysed the relationship between industry funding and organisational positions on a range of highly controversial issues. Industry funded groups generally supported sponsors' interests. CONCLUSION: In general, industry funding of patient groups seems to be common, with prevalence estimates ranging from 20% to 83%. Few patient groups have policies that govern corporate sponsorship. Transparency about corporate funding is also inadequate. Among the few studies that examined associations between industry funding and organisational positions, industry funded groups tended to have positions favourable to the sponsor. Patient groups have an important role in advocacy, education, and research, therefore strategies are needed to prevent biases that could favour the interests of sponsors above those of the public. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017079265.

Effects of lifestyle and diet on bone health in young adult Chinese women living in Hong Kong and Beijing.

BACKGROUND: Dietary and lifestyle variations may be too small to detect possible associations with bone mineral density (BMD) within a community. Pooled data from communities with different diets and lifestyle but of the same ethnicity may help explore these associations. OBJECTIVE: To examine the effects of dietary and lifestyle factors on BMD in young Chinese women. METHODS: Baseline data were analyzed from 441 women aged 20 to 35 years in Hong Kong and Beijing who were participating in a longitudinal study evaluating the effect of milk supplementation on bone health. Data on demographic characteristics, lifestyle, use of oral contraceptives, diet, physical activity, and BMD of total hip, femoral neck, and total spine measured by dual-energy x-ray absorptiometry were pooled for analysis. RESULTS: Hong Kong subjects had significantly lower BMD and higher body-size-adjusted dietary intakes of protein, fat, fiber, vitamins, potassium, sodium, and selenium than Beijing subjects. Multivariate regression of pooled data showed that body mass index was the most important determinant of BMD at all sites. Age was negatively associated and use of oral contraceptives was positively associated with femoral neck BMD. Carbohydrate intake was positively associated with total hip BMD. Fiber intake was negatively associated with BMD at total hip and total spine. Increased vitamin E intake was associated with greater total spine BMD. None of the nutrients were associated with BMD at the femoral neck. CONCLUSIONS: Diet, lifestyle, and BMD differed greatly between young women from Hong Kong and Beijing. Body mass index was the most important determinant of BMD in young Chinese women, whereas age, use of oral contraceptives, and diet had less pronounced effects.

How do health consumer organisations in Australia manage pharmaceutical industry sponsorship? A cross-sectional study.

Objective The aim of this study was to investigate how health consumer organisations manage their relationships with the pharmaceutical industry in Australia. Methods We identified 230 health consumer organisations that received pharmaceutical industry support from 2013 to 2016 according to reports published by Medicines Australia, the industry trade association. A random sample of 133 organisations was selected and their websites assessed for financial transparency, policies governing corporate sponsorship and evidence of potential industry influence. Results In all, 130 of the 133 organisations evaluated received industry funding. Of these 130, 68 (52.3%; 95% confidence interval (CI) 43.4-61.1%) disclosed this funding. Nearly all (67; 98.5%) reported the identity of their industry donors, followed by uses (52.9%), amount (13.2%) and proportion of income from industry (4.4%). Less than one-fifth (24/133; 18.0%; 95% CI 11.9-25.6%) had publicly available policies on corporate sponsorship. Six organisations (7.2%; 95% CI 2.7-15.1%) had board members that were currently or previously employed by pharmaceutical companies, and 49 (36.8%; 95% CI 28.6-45.6%) had company logos, web links or advertisements on their websites. Conclusion Industry-funded health consumer organisations in Australia have low transparency when reporting industry funding and few have policies governing corporate sponsorship. Relationships between health consumer organisations and the industry require effective actions to minimise the risks of undue influence. What is known about this topic? Pharmaceutical industry funding of health consumer organisations is common in the US and Europe, yet only a minority of such organisations publicly disclose this funding and have policies regulating their relationships with industry. What does this paper add? Industry-funded health consumer organisations in Australia have inadequate financial transparency and rarely have policies addressing corporate funding. Organisations that have received more industry funding are more likely to report it publicly. What are the implications for practitioners? Robust policies addressing corporate sponsorship and increased transparency are needed to maintain the independence of health consumer organisations. Governments may also consider regulating non-profit organisations to ensure public reporting of funding sources.

Pharmaceutical Industry Funding of Health Consumer Groups in Australia: A Cross-sectional Analysis.

Relationships between consumer organizations and pharmaceutical manufacturers are the focus of transparency efforts in some jurisdictions, including Australia. This study describes the frequency and nature of industry sponsorship of Australian health consumer organizations and examines the link between sponsorship of the most highly funded organizations and manufacturers' requests for public reimbursement of products for related health conditions. We downloaded 130 transparency reports covering the period January 2013 to December 2016 from the website of Medicines Australia and carried out a descriptive analysis. For the most heavily funded organizations and their sponsors, we examined Public Summary Documents of the Pharmaceutical Benefits Advisory Committee to identify relevant products under consideration for public reimbursement over the study period. Thirty-four pharmaceutical companies provided 1,482 sponsorships to 230 organizations, spending a total of AU$34,507,810. The top clinical areas in terms of amount of funding received were cancer, eye health, and nervous system disorders. The sponsors of the most highly funded groups were companies that in most cases had drugs under review for public reimbursement for conditions covered by these organizations. Interactions between the pharmaceutical industry and consumer organizations are common and require careful management to prevent biases that may favor sponsors' interests above those of patients and the public.

Very high rates of vitamin D insufficiency in women of child-bearing age living in Beijing and Hong Kong.

We aimed to describe the vitamin D status of young women living in two Chinese cities in the spring--Beijing in the north (latitude 39 degrees north) and Hong Kong (latitude 22 degrees north) in the south. We also examined the relationship between serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations to determine a threshold for serum 25-hydroxyvitamin D above which there is no further suppression of PTH. Finally, we examined whether dietary Ca intake influences this relationship. Non-pregnant women aged 18-40 years (n 441) were recruited between February and June. Fasting blood was collected and dietary intakes were assessed using 5 d food records. Mean serum 25-hydroxyvitamin D concentration was lower in Beijing than Hong Kong women (29 v. 34 nmol/l; P < 0.001). Vitamin D deficiency (< or = 25 nmol/l) was indicated in 40% of Beijing and 18% of Hong Kong women, and over 90% of women in both cities were insufficient (< or = 50 nmol/l). Mean Ca and vitamin D intakes were 478 mg/d and 2.0 microg/d, respectively. The relationship between 25-hydroxyvitamin D concentration and PTH was linear throughout the range with a slope of -0.36 (different from 0; P < 0.001; R 0.26), with no apparent threshold. There was no influence of Ca intake on the relationship between 25-hydroxyvitamin D and PTH concentration. Vitamin D deficiency is common and insufficiency is very common in non-pregnant women in Hong Kong and Beijing during spring. Serum 25-hydroxyvitamin D was inversely associated with PTH with no apparent threshold. Strategies such as vitamin D fortification or supplementation may be required.

Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.

UNLABELLED: The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

Milk supplementation and bone health in young adult chinese women.

BACKGROUND: Milk is potentially beneficial for bone health, particularly for Chinese populations where consumption of dairy products is low. There are few data about milk consumption by Chinese women aged 20-35 years. This study examines whether milk supplement over 2 years caused increased bone mineral density (BMD) in Chinese women aged 20-35 years. METHODS: Four hundred forty-one community-living women living in Hong Kong SAR (221) and Beijing (220) China were randomized to receive milk supplement or nothing. The supplement consisted of two sachets of milk powder (1000 mg calcium, 80 microg vitamin K(1)), for 24 months. BMD at total hip, total spine, and whole body was measured at baseline and at 6, 12, 18, and 24 months; blood specimens were analyzed at baseline and at 3 and 24 months for biochemical indices of bone turnover and vitamin K. Urine samples also were collected. Analysis was by intention to treat as well as per protocol. Differences in change from baseline between the milk and control groups were analyzed using the mixed models approach to repeated measures, including the baseline value as a covariate. RESULTS: Both groups had an increase in BMD and a decrease in bone turnover markers over time, as an indicator of the process of attainment of peak bone mass during this period. Apart from a higher total spine BMD at 6 months in the milk group using per protocol analysis, there was little significant difference observed between the milk group and the control group. CONCLUSIONS: Age-related bone metabolism and lack of compliance most likely explain the lack of consistent changes in BMD or bone biochemical measures in response to milk supplementation for 2 years in Chinese women aged 20-35 years.

Associated factors and health impact of sarcopenia in older chinese men and women: a cross-sectional study.

BACKGROUND: Sarcopenia is increasingly being recognized as a feature of frailty in old age and is associated with unfavorable health outcomes in Western populations. Little is known about sarcopenia among Asian elderly populations. OBJECTIVES: The study was undertaken to study the association between sarcopenia and common chronic illnesses, lifestyle factors, psychosocial well-being and physical performance. METHODS: 4,000 community-dwelling Chinese elderly >/=65 years were recruited. Medical illnesses, cigarette smoking, alcohol consumption, physical activity level and psychosocial well-being scores were recorded. Physical performance measured included grip strength, timed chair-stands, stride length and a timed 6-meter walk. Muscle mass was measured using dual-energy X-ray absorptiometry. Relationships between appendicular skeletal muscle mass (ASM/ht(2)) and multiple variables were analyzed using uni- and multivariate analyses. RESULTS: Mean ASM/ht(2) was 7.19 and 6.05 kg/m(2) in men and women respectively. Older age, cigarette smoking, chronic lung disease, atherosclerosis, underweight, and physical inactivity were associated with low adjusted ASM, which was in turn associated with poorer physical well-being in men. After adjustment to age, lower appendicular muscle mass was associated with weaker grip strength in both sexes. In men, lower limb tests (chair-stands, walking speed and step length) were not related to ASM, while in women, lower muscle mass was not associated with poorer lower limb muscle performance. CONCLUSIONS: Sarcopenia in community-dwelling older Chinese men and women was associated with cigarette smoking, chronic illnesses, underweight, physical inactivity, poorer well-being and upper limb physical performance.

A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D.

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8mg/d) or placebo for 36months. The primary endpoint was the proportion of patients with a new vertebral fracture. The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (±0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (±0.12%) increase in the placebo group by the end of the study (p<0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24months, but not at 36months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected. Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related. Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.

Prevalence of and risk factors for sarcopenia in elderly Chinese men and women.

BACKGROUND: Several studies have documented the substantial health and economic burdens associated with sarcopenia among the elderly, but there has been no systematic study among Asians. A cross-sectional survey of elderly community-dwelling Chinese volunteers (262 men and 265 women), aged 70 years and older, was undertaken in Hong Kong. The purposes of this study were to evaluate the prevalence of and risk factors for sarcopenia in elderly Chinese, and to compare these observations with those in white persons. METHODS: Muscle mass was estimated by dual-energy X-ray absorptiometry. In this study, sarcopenia was defined as a total adjusted skeletal muscle mass two standard deviations or more below the normal mean for young Asian men and women in this study. The relationship between risk factors (alcohol consumption, cigarette smoking, regular exercise, body mass index, medical conditions) and sarcopenia was studied by multiple logistic regression. RESULTS: The prevalence of sarcopenia was 12.3% in Chinese men and 7.6% in Chinese women aged 70 years and older, which was slightly lower than figures observed in white persons. Being underweight was a significant risk factor in both men (odds ratio, 39.1; 95% confidence interval, 11.3 to 134.6) and women (odds ratio, 9.7; 95% confidence interval, 2.8 to 33.8). No other risk factors were found in Chinese men or women. CONCLUSIONS: Sarcopenia exists among elderly Chinese men and women, albeit at a lower rate than in white persons. This may be due to the lower muscle mass among young men and women or to an attenuated rate of loss in muscle mass with aging in the Chinese elderly. Being underweight is a major risk factor for sarcopenia in both sexes.

Dose effects of progesterone in add-back therapy during GnRHa treatment.

OBJECTIVE: To compare 1 mg norethisterone acetate with 5 mg norethindrone when used in conjunction with 2 mg estradiol given as add-back therapy during treatment with a gonadotropin-releasing hormone agonist (GnRHa). STUDY DESIGN: A prospective, double-blind, randomized study was conducted in a university-based teaching hospital. Forty-seven patients with pelvic endometriosis were recruited. Subcutaneous GnRHa was administered at 6-week intervals, and add-back therapy was commenced with the second dose of GnRHa. Group A patients received 2 mg estradiol and 1 mg norethisterone acetate, while group B patients received 2 mg estradiol and 5 mg norethindrone daily. Changes in bone mineral density, menopausal symptoms, lipid profile and occurrence of breakthrough bleeding were assessed before and after treatment. RESULTS: Patients in group A had no significant bone loss and satisfactory control of menopausal symptoms. The additional dose of progestogen in group B had a deleterious effect on the lipid profile and increased the frequency of breakthrough bleeding. CONCLUSION: In this study, the benefits of add-back therapy during GnRHa treatment were not enhanced, and a deleterious effect upon the lipid profile was seen when using a constant dosage of 2 mg estradiol and 5 mg norethindrone as compared to 1 mg norethisterone acetate.

Osteoporosis and the global competition for health care resources.

Global aging superimposed on existing infectious diseases and trauma will aggravate competition for health care resources to diagnose and treat osteoporosis. Efforts to implement public health measures are needed, but the targeted approach to assessment and treatment of high-risk individuals must also be refined. Increases in the elderly population worldwide will cause a dramatic rise in osteoporotic fractures, but other age-related diseases will increase as well. Changes will be superimposed on existing public health problems (e.g., malaria, alcoholism), and these acute health care needs will take priority in some areas. Societies in most parts of the world may have to limit osteoporosis control to broad public health measures, and such efforts (e.g., calcium and vitamin D supplementation) should be supported. In these regions, clinical decision-making will generally be limited to treating patients with fractures (who presumably have already failed any public health measures in place), or in a few wealthy countries, to patients with low bone density identified by case-finding. Case-finding approaches will vary with the resources available, although unselective (mass) screening by bone densitometry is largely ineffective and unaffordable anywhere. The key to clinical decision-making on behalf of individuals will be an assessment of absolute fracture risk, and the tools needed to predict the risk of an osteoporotic fracture over the next 10 years are now being developed. These include bone density measures, but also incorporate other risk factors (e.g., fracture history, corticosteroid use), which may allow extension of fracture risk prediction to nonwhite populations and to men. Even with a universal risk prediction tool, cost-effective treatment thresholds will vary by country based on the level of fracture risk in the region and on the resources available for health care. To better compete for these resources, efforts should be made to lower the cost of osteoporosis interventions. Additionally, evidence is needed that these interventions are really effective in reducing fractures in the community.

Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.

OBJECTIVE: Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. DESIGN: To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. RESULTS: Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. CONCLUSIONS: This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.

Increasing insulin resistance contributes to worsening glycaemic and lipid profiles in older Chinese subjects.

OBJECTIVE: To investigate the impact of insulin resistance on cardiovascular risk factors in the elderly. RESEARCH DESIGN AND METHODS: A cross-sectional, community-based study of 225 older Chinese participants (65-74 years, 55.6% female) recruited from community centres for the elderly in Shatin. Anthropometric measures and DXA body fat, blood pressure, insulin sensitivity (fasting insulin, fasting insulin-glucose product, short insulin tolerance test (SITT)), glycaemic (fasting glucose, glycated haemoglobin A1c) and lipid (total, HDL-, and LDL-cholesterol, triglycerides) indices and albuminuria (24h albumin-to-creatinine ratio) were measured. RESULTS: There was a close correlation between the SITT and insulin-glucose product indices of insulin resistance. Decreasing tertiles of insulin sensitivity were associated with increasing indices of glycaemic control, and general and central obesity, including DXA lean and fat mass, albuminuria, and triglycerides, with decreasing HDL-cholesterol. There were no differences in blood pressure or electrolyte levels between these tertile groups. These subjects were more insulin resistant than a group of younger diabetics. CONCLUSIONS: Insulin resistance was associated with indices of obesity and an atherogenic lipid and hyperglycaemic profile and may in part contribute to the high frequency of metabolic syndrome components in these older Chinese subjects.