Vitamin D status and falls, frailty, and fractures among postmenopausal Japanese women living in Hawaii.

UNLABELLED: Vitamin D status and its relationship to physical performance, falls, and fractures in 495 postmenopausal women of Japanese ancestry in Hawaii were investigated. The mean 25-hydroxyvitamin D (25-OHD) was 31.94 ng/mL. No significant association of 25-OHD was demonstrated with most outcomes, possibly due to higher 25-OHD levels in this population. INTRODUCTION: In this study, we investigated vitamin D status and its relationship to physical performance, muscle strength, falls, and fractures in postmenopausal Japanese females living in Hawaii. METHODS: Of 510 community-dwelling women who participated in the eighth examination of the Hawaii Osteoporosis Study, 495 were included in these analyses. Multivariate regression models were used to evaluate the relationship of 25-OHD (D(3) and total) to eight performance-based measurements, 12 activities of daily living (ADLs), and muscle strength (grip, triceps, and quadriceps). Logistic regression analyses were performed to evaluate the relationship of 25-OHD to falls, vertebral fractures, and non-vertebral fractures. RESULTS: The mean total 25-OHD was 31.94 +/- 9.46 ng/mL; 44% of subjects had values <30 ng/mL, while none had values <10-12 ng/mL. There was little evidence of seasonal variation. Among performance-based measures, ADLs, and strength tests, only quadriceps strength was significantly associated with total 25-OHD (p = 0.0063) and 25-OHD(3) (p = 0.0001). No significant association of 25-OHD was found with vertebral or non-vertebral fractures, or incidence of one or more falls. CONCLUSIONS: Lack of serum 25-OHD relationship with falls and fractures or most physical performance measures in this study may be related to the low prevalence of very low 25-OHD levels in this population.

Alendronate in the prevention of osteoporosis: 7-year follow-up.

In a 3-year study followed by a 2-year open-label extension, alendronate sodium (ALN) maintained or increased bone mineral density (BMD) in 445 recently postmenopausal women with a spine BMD T-score >-2. In a second 2-year extension, 84 women previously treated with either 5 or 10 mg ALN daily during the first 3 years and 5 mg ALN during the first extension (group A) were randomized to either 5 mg ALN or placebo (PBO). Another group of 59 women (group B) received 20 mg ALN during the first 2 years, PBO during year 3, and were then followed up without treatment during years 4-7. In group A, continuous ALN treatment for 7 years increased spine and trochanter BMD by 2.7-4.1 and 3.3-4.2%, respectively, while femoral neck BMD was maintained. Patients initially receiving 10 mg ALN maintained total body BMD, whereas those treated with 5 mg ALN experienced a small but significant loss after 7 years. Among women who received ALN 5 mg during years 4-7, those who had been treated with ALN 10 mg in the first 3 years had slightly greater increases in BMD at most sites at the end of the study, compared with women who received ALN 5 mg during the first 3 years. During years 6-7, patients who switched to PBO during the previous 2 years showed a significant loss in femoral neck BMD, whereas changes at the other sites were not significant. Women in group B showed significant loss in BMD at all skeletal sites during years 4-7, when they received no treatment. In conclusion, ALN 5 or 10 mg daily for up to 7 years prevents bone loss in recently postmenopausal women. Patients started on ALN 10 mg appear to gain more BMD than those initially treated with 5 mg ALN. Early postmenopausal women who discontinue ALN after 2 years of treatment experience significant bone loss at all skeletal sites despite the higher (20 mg) initial dosing. The ALN was generally well tolerated during 7 years of treatment.

Comparison of performance-based measures among native Japanese, Japanese-Americans in Hawaii and Caucasian women in the United States, ages 65 years and over: a cross-sectional study.

BACKGROUND: Japanese (both in Japan and Hawaii) have a lower incidence of falls and of hip fracture than North American and European Caucasians, but the reasons for these differences are not clear. SUBJECTS AND METHODS: A cross-sectional study. We compared neuromuscular risk factors for falls using performance-based measures (chair stand time, usual and rapid walking speed, and grip strength) among 163 Japanese women in Japan, 681 Japanese-American women in Hawaii and 9403 Caucasian women in the United States aged 65 years and over. RESULTS: After adjusting for age, the Caucasian women required about 40% more time to complete 5 chair stands than either group of Japanese. Walking speed was about 10% slower among Caucasians than native Japanese, whereas Japanese-American women in Hawaii walked about 11% faster than native Japanese. Grip strength was greatest in Japan, which may reflect the rural farming district that this sample was drawn from. Additional adjustment for height, weight or body mass index increased the adjusted means of chair stand time and grip strength among Japanese, but the differences remained significant. CONCLUSIONS: Both native Japanese and Japanese-American women in Hawaii performed better than Caucasians on chair stand time and walking speed tests, and native Japanese had greater grip strength than Japanese in Hawaii and Caucasians. The biological implications of these differences in performance are uncertain, but may be useful in planning future comparisons between populations.

The relation between lifestyle factors and biochemical markers of bone turnover among early postmenopausal women.

We examined the associations of two biochemical markers of bone turnover with lifestyle factors in 340 postmenopausal women in Hawaii, ages 45-59 years, from the Early Postmenopausal Intervention Cohort. Physical activity, calcium supplement use, smoking and alcohol use in the prior 2 weeks were measured and examined as independent variables in multiple regression analyses with bone turnover markers as dependent variables, adjusted for weight, height, whole body bone mass, serum estradiol, years since menopause, and ethnicity. Calcium supplement and alcohol use were significantly associated with reduced levels of urinary type I collagen cross-linked N-telopeptides (NTX). The mean NTX level was 12% lower among women using > or = 250 mg of calcium supplements per day as compared with other women, and 20% lower among alcohol users compared with nonusers. Both calcium supplement use and alcohol intake were associated with lower mean serum osteocalcin (a marker of bone formation) and NTX z-scores. By contrast, smoking was associated with lower osteocalcin levels, without any effect on NTX. The osteocalcin level was 12% lower among smokers compared with nonsmokers. In addition, the z-score difference between NTX and osteocalcin was significantly associated with smoking, with a shift towards more NTX than osteocalcin. Physical activity was not significantly associated with either of the markers. These findings suggest that biochemical markers may help to identify lifestyle factors that affect bone, and provide estimates of the relative magnitude of these effects on bone formation and resorption, independent of each other.

Effects of high versus low-intensity resistance training on bone mineral density in young males.

The purpose of this study was to investigate the effect of high-intensity and low-intensity resistance training upon bone mineral density (BMD) by comparing the BMD of young male powerlifters (n = 5), recreational trainees (n = 5), and controls (n = 5). Lumbar spine (L2-L4), proximal femur, and whole body BMDs were measured using dual-energy X-ray absorptiometry (DXA). The high-intensity group showed a significantly greater BMD when the whole body and trochanter regions were measured than the low-intensity and control group. The BMD of the lumbar spine, femoral neck, and Ward's triangle was greater in the high-intensity group compared with the control group. There was no significant BMD difference between the low-intensity and control group except at the trochanter region. These results suggest that high-intensity resistance training is effective for increasing BMD, but low-intensity resistance training is not.

Low bone density is not associated with aortic calcification.

The aging process is associated with an increasing prevalence of osteoporosis and aortic calcification, but it is uncertain if these two conditions are interrelated. We examined the relationship between bone mineral density (BMD) and evidence of aortic calcification on spinal radiographs among 524 Japanese-American women living in Hawaii. The prevalence of aortic calcification increased with age from less than 10% below age 55 to essentially all women over age 75. Unadjusted BMD was significantly lower among women with aortic calcification at all measured sites (distal and proximal radius and calcaneus). However, the differences in BMD between women with and without calcification were diminished and no longer significant after adjustment for age. Aortic calcification was positively associated with body mass index (BMI), systolic blood pressure, diabetes, current smoking, and thiazide use, but negatively associated with physical activity index. Multivariate logistic regression analysis showed that age, systolic blood pressure, physical activity index (protective), and current smoking (common etiological factors for aortic calcification) were independently associated with aortic calcification, whereas BMD (mean Z-score) was not. We conclude that there is little evidence to support a direct relationship between osteoporosis (low BMD) and aortic calcification. Osteoporosis and aortic calcification appear to be independent processes that occur as women age. However, potential confounding factors may be involved, and prospective studies are needed to investigate this issue further.

Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group.

We report here the second 2-yr extension of a clinical trial among postmenopausal women; 235 women continued blinded treatment with 5 or 10 mg alendronate daily, and 115 women who had been treated with alendronate for 5 yr were switched to blinded placebo. Continuous treatment with alendronate (10 mg daily) for 7 yr increased lumbar spine bone mineral density (BMD) by 11.4% compared to baseline. After the initial 18 months, each additional year of treatment through yr 7 increased spine BMD by 0.8% for the 10-mg dose and 0.6% for the 5-mg dose, with significant increases during yr 6-7. Previously reported increases in BMD at other skeletal sites and decreases in biochemical markers of bone turnover remained stable during yr 6-7. Among women previously taking alendronate for 5 yr who were switched to placebo, there was no significant decline in BMD at the spine or hip, whereas small, but significant, decreases in BMD at the forearm and total body and small increases in biochemical markers were observed. The safety and tolerability profiles were similar to those of placebo. This is the largest published long-term study of antiresorptive therapy. Our findings indicate that long-term alendronate treatment is well tolerated and effective for 7 yr. Increases in spinal BMD continue for at least 7 yr, and other skeletal benefits are maintained. Discontinuation does not lead to accelerated bone loss, but continuous treatment yields better skeletal benefits than shorter treatment.

Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group.

We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263 consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr of placebo followed by alendronate (5 mg) for 2 yr (group II), and 52 received alendronate (20 mg) for 2 yr followed by 3 yr off therapy (group III). In group I, alendronate (5 mg) increased bone mineral density (BMD) at the spine and trochanter by 2.5-3.2% (P < 0.001 vs. baseline) and stabilized total body and femoral neck BMD (change vs. baseline, P = NS) over 5 yr. By the end of 5 yr, BMD was comparable at the spine, hip, and total body in groups I and III. The 3-yr decrease in BMD after withdrawal of alendronate (20 mg) in group III was 1.8-5.7% (P < 0.01 vs. baseline) and similar to the 3-yr decrease in BMD in group II during the initial 3 yr. In conclusion, alendronate (5 mg) for 5 yr or alendronate (20 mg) for 2 yr followed by 3 yr off therapy prevented postmenopausal bone loss. After withdrawal of alendronate (20 mg), bone loss resumed at the normal early postmenopausal rate.

Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study.

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.

Antifracture efficacy of antiresorptive agents are related to changes in bone density.

There is a current debate about the extent to which antifracture efficacy of antiresorptive drugs are related to changes in bone mineral density (BMD). In vitro studies show that most of the variability in bone strength is related to BMD, and prospective studies have shown that low BMD is an important predictor of fracture risk. It seems that higher levels of bone turnover are also associated with increased fracture risk. Over the short term, a reduction in activation frequency or resorption depth would lead to fewer (and/or shallower) resorption sites and refilling of existing sites initially. There is also evidence that inhibiting resorption allows bone to respond to mechanical demands, preferentially thickening critical trabeculae, and this may help compensate for reduced connectivity. Each of these mechanisms would increase BMD and would disproportionately improve bone strength. Over the long term, maintaining bone mass and preventing loss of structural elements would result in progressively greater differences in BMD and fracture risk over time, relative to untreated women. The conceptual model predicts that both the short- and long-term antifracture efficacy of antiresorptive drugs will depend on the extent to which treatment can increase and maintain BMD. To examine this issue, we compiled data from clinical trials of antiresorptive agents and plotted the relative risk of vertebral fractures against the average change in BMD for each trial. The confidence intervals are large for individual trials, and there was substantial variability in antifracture efficacy at any given level of change in BMD. Overall, however, trials that reported larger increases in BMD tended to observe greater reductions in vertebral fracture risk. Poisson regression was used to quantify this relationship. The model predicts that treatments that increase spine BMD by 8% would reduce risk by 54%; most of the total effect of treatment was explained by the 8% increase in BMD (41% risk reduction). These findings are consistent with the short-term predictions of the conceptual model and with reports from randomized trials. The small but significant reductions in risk that were not explained by measurable changes in BMD might be related to publication bias, measurement errors, or limitations of current BMD technology.

Relation between body composition and biochemical markers of bone turnover among early postmenopausal women.

We studied the associations between body composition and biochemical markers of bone formation and resorption among 1600 postmenopausal women, ages 45-59. Multiple regression analyses were performed to examine the independent associations of fat mass, muscle strength (quadriceps strength), height, and whole body bone mineral content (BMC) with biochemical markers of bone formation (serum osteocalcin) and resorption (urinary type I collagen crosslinked N-telopeptides [NTX]). Per interquartile range (IQR) (the difference between 75th and 25th percentiles) increase in fat mass and whole body BMC, the mean levels of osteocalcin decreased by 3% and 13%, respectively; NTX decreased by 5 and 21%. Fat mass and whole-body BMC were also significantly associated with decreases in the average of osteocalcin and NTX Z-scores. By contrast, the mean levels of serum osteocalcin increased by 2 and 11%, respectively, per IQR increase in muscle strength and height; NTX increased by 4 (not significant) and 14%, respectively. Both muscle strength and height were significantly associated with increases in the average Z-scores. These exploratory analyses suggest that fat mass and whole-body BMC were associated with decreased bone turnover, while muscle strength and height were associated with increased bone turnover.

Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial.

BACKGROUND: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. OBJECTIVE: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. DESIGN: Randomized, controlled trial. SETTING: United States and Europe. PARTICIPANTS: 1609 postmenopausal women 45 to 59 years of age. INTERVENTION: Participants were randomly assigned to receive oral alendronate, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen-progestin. Women in the alendronate groups received alendronate for the first 2 years of the study. Treatment was then continued without change or replaced with placebo for the last 2 years of the study. MEASUREMENTS: Annual measurement of bone mineral density. RESULTS: By year 4, the bone mineral density of participants in the placebo group had decreased by 1% to 6% (P < 0.001). Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine (mean change [+/-SE], 3.8%+/-0.3%), hip (mean, 2.9%+/-0.2%), and total body (mean, 0.9%+/-0.2%) (P < 0.001 overall). By year 4, bone mineral density at most skeletal sites was greater in participants who switched from alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater. CONCLUSIONS: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after alendronate therapy was stopped; however, continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo.

Skeletal benefits of two years of alendronate treatment are similar for early postmenopausal Asian and Caucasian women.

Alendronate has been shown to increase bone density among early postmenopausal women. Osteoporosis is common among both Asian and Caucasian women, but most clinical trials have consisted primarily of Caucasian women, and it does not appear that the effectiveness of antiresorptive agents such as alendronate has been compared between the two races. In this study we compared the response of bone density and biochemical markers to alendronate among 136 Asian and 126 Caucasian women who participated in the Early Postmenopausal Interventional Cohort (EPIC) at the Hawaii center. Approximately 40 women of each race were randomly assigned to placebo or to 2.5 mg/day or 5 mg/day alendronate. Bone mineral density (BMD) was measured at the spine, total hip and total body at baseline, 12 months and 24 months; biochemical markers of bone turnover were measured at 6-month intervals. Responses were greater for the 5 mg dose than 2.5 mg, and were similar in the two races. For example, mean (SE) changes in spine BMD at 24 months for Caucasians and Asians, respectively, were -1.9% (0.5%) and -1.9% (0.4%) for the placebo group, 2.0% (0.5%) and 3.4% (0.5%) at 2.5 mg/day and 4.2% (0. 5%) for both races at 5 mg/day. Corresponding changes in urinary N-telopeptide collagen crosslinks were -33.6% (5.6%) and -27.8% (5. 8%) for placebo, -51.4% (4.0%) and -62.1 (4.3%) at 2.5 mg/day and -70.8% (2.4%) and -73.5% (3.1%) at 5 mg/day. We conclude that (1) the rate of bone loss in untreated Asian and Caucasian postmenopausal women is similar, with the possible exception of the hip; (2) 5 mg alendronate daily provides greater skeletal benefits than 2.5 mg/day in both Asian and Caucasian early postmenopausal women; and (3) the response at 5 mg/day is similar in the two races.

Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group.

Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p

Ethnic, anthropometric, and lifestyle associations with regional variations in peak bone mass.

The study investigated the ability of ethnicity and anthropometric and lifestyle factors to account for differences within subjects in bone mass at different skeletal sites. The subjects were young, adult, Japanese, Filipino, Hawaiian, and white women ages 25-34. In the preliminary analyses, they were divided into thirds based on their BMD z-scores. Thirty-five percent exhibited high variability in bone mass: they were in the upper third at one or more bone sites and in the lower third at one or more sites. Other women had more generalized low bone mass: 25% were in the lowest third for two or more sites, and there were no sites with low bone mass in the upper third. In subsequent analyses, ethnicity, anthropometry, and lifestyle influences were examined as possible predictors of differences in bone mineral content (BMC) between bone sites in bone-size adjusted models. White women had greater BMC at the proximal radius and calcaneus than at the distal radius compared with other ethnic groups. This may be explained by the fact that they had exceptionally wide bone widths at the distal radius. Of the anthropometric variables, fat mass was associated with higher bone mass at sites with higher proportions of cancellous tissue (calcaneus > spine > radius sites). Muscle mass was associated with greater bone mass at the calcaneus and proximal radius than at the spine. For the lifestyle variables, women with greater milk consumption between the ages of 10-24 years had higher spine bone mass than expected from their measurements at the proximal radius. Women 12-17 years of age who had been more active in sports had higher calcaneous bone mass than expected from their spine measurements. As the study participants were still young women, the results suggest that regional differences in bone mass may partly derive from anthropometric and lifestyle influences during skeletal maturation.

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.

A cross-cultural comparison of neuromuscular performance, functional status, and falls between Japanese and white women.

BACKGROUND: Previous studies have reported that the incidence of falls among Japanese women is about half that of white women. The difference in incidence might result from differences in neuromuscular performance, such as muscle strength, mobility, and balance. This hypothesis was tested by comparing two community-dwelling populations: Japanese women in the Hawaii Osteoporosis Study, and Caucasian women in the Study of Osteoporotic Fractures. METHODS: Neuromuscular performance was assessed for women in the two cohorts using standardized procedures. Falls were monitored longitudinally, using surveys mailed at 4-month intervals. RESULTS: The Japanese and white women differed substantially in their neuromuscular performance. The Japanese women had faster walking speeds and chair stands, and performed better on a series of balance tests. The white women had greater strength, particularly at the quadriceps, and faster hand and foot reaction times. The white women also reported fewer functional disabilities, including fewer difficulties in climbing steps, doing heavy housework, and shopping for groceries. In age-adjusted analyses, the risk of falls was greater for the white women [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.6, 2.0]. After adjusting for the neuromuscular test results and the number of functional disabilities, the odds ratio for the risk of falls remained essentially the same (OR = 1.8; 95% CI = 1.5, 2.1). CONCLUSIONS: The Japanese and white women had different advantages and limitations in neuromuscular performance. These differences, however, did not explain the lower risk of falls among Japanese women.

Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study.

To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg), change from baseline at month 6 in urine N-telopeptide cross-links of type I collagen (NTX) and osteocalcin (OC) correlated with change from baseline at month 24 in spine, hip, and total body bone mineral density (BMD) [r = -0.28 to -0.31 (NTX) and r = -0.16 to -0.25 (OC), P<0.001]. This corresponded to a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut-point, validly identified women who responded, on ALN treatment, with a stabilization or an increase in bone mass. However, lack of decrease below the cut-point in NTX or OC could not be used to identify women with a bone loss during ALN treatment.

Risk factors for falls and for serious injuries on falling among older Japanese women in Hawaii.

OBJECTIVES: To evaluate if similar constellations of factors underlie the risks of falls and injuries on falling for Japanese women as reported for predominately white populations. DESIGN: A prospective cohort study SETTING: The island of Oahu PARTICIPANTS: The older Japanese women who participated in the Hawaii Osteoporosis Study (mean age = 74 +/- 5 (SD) years). MEASUREMENTS: As outcomes: falls and serious injuries on falling. As predictors: anthropometric measurements, measurements of neuromuscular performance, activities of daily living (ADLs), past falls, and other suspected risk factors for falls and serious injuries. RESULTS: In multivariable models, four subject characteristics were positively associated with having a fall (having a fall in the past year (RR = 2.0 (95% CI, 1.5-2.8)), slow chair stands (RR = 1.4 (95% CI, 1.0-1.9), a short height (RR = 1.5 (95% CI, 1.1-2.1)), difficulties with five or more ADLs (RR = 1.5 (95% CI, 1.1-2.1))). Two subject characteristics were negatively associated with having a fall (ability to perform a full tandem balance with eyes closed (RR = .7 (95% CI, .5-1.0)) and having a long functional reach (RR = .7 (95% CI, .5-1.0))). The RRs represent as nearly as possible comparisons of the upper (or lower) quartile and the remaining quartiles. In multivariable models, long times for chair stands (odds ratio (OR) = 3.0 (95% CI, 1.5-6.1)) and a low BMI (OR = 3.1 (95% CI, 1.5-6.4)) were positively associated with having a serious injury among women who had a fall. Among the same women, taking part in an activity they did frequently (OR = .3 (95% CI, .1-.8)) and slow foot reaction times (OR = .3 (95% CI, .1-.8)) were associated negatively with having a serious injury. CONCLUSIONS: The results from this Japanese cohort support the conclusion that women at high risk of falling and serious fall injuries can be identified using a questionnaire and simple, performance-based tests of neuromuscular function. The risk factors for falling overlapped, but were distinct from, those for suffering a serious injury once a fall had occurred.