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OBJECTIVE: Despite advances in incorporating diversity and structural competency into medical education curriculum, there is limited curriculum for public health research professionals. We developed and implemented a four-part diversity, equity, and inclusion (DEI) training series tailored for academic health research professionals to increase foundational knowledge of core diversity concepts and improve skills. METHODS: We analyzed close- and open-ended attendee survey data to evaluate within- and between-session changes in DEI knowledge and perceived skills. RESULTS: Over the four sessions, workshop attendance ranged from 45 to 82 attendees from our 250-person academic department and represented a mix of staff (64%), faculty (25%), and trainees (11%). Most identified as female (74%), 28% as a member of an underrepresented racial and ethnic minority (URM) group, and 17% as LGBTQI. During all four sessions, attendees increased their level of DEI knowledge, and within sessions two through four, attendees perception of DEI skills increased. We observed increased situational DEI awareness as higher proportions of attendees noted disparities in mentoring and opportunities for advancement/promotion. An increase in a perceived lack of DEI in the workplace as a problem was observed; but only statistically significant among URM attendees. DISCUSSION: Developing applied curricula yielded measurable improvements in knowledge and skills for a diverse health research department of faculty, staff, and students. Nesting this training within a more extensive program of departmental activities to improve climate and address systematic exclusion likely contributed to the series success. Additional research is underway to understand the series longer-term impact on applying skills for behavior change.

OBJECTIVE: Hearing loss (HL) is highly prevalent among older adults and may lead to increased risk of depressive symptoms. In both cross-sectional and longitudinal analysis, we quantified the association between HL and depressive symptoms, incorporating the variable nature of depressive symptoms and characterizing by race and gender. METHODS: Data were from the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Study Depression Scale short form (CES-D 10), defined as CES-D 10 score ≥10 or treatment for depression. Hearing was defined via four-frequency pure-tone average (PTA) decibel hearing level (dB HL), categorized as normal hearing (PTA ≤25 dB HL), mild HL (PTA26-40 dB HL), and ≥moderate HL (PTA > 40 dB HL). Associations at baseline were quantified using logistic regression, incident depressive symptoms using Cox proportional hazard models, and change in depressive symptoms over time using growth mixture models and multinomial logistic regression. RESULTS: Among 2,089 older adults (1,082 women, 793 Black; mean age 74.0 SD: 2.8), moderate or greater HL was associated with greater odds of concurrent [Odds Ratio (OR):2.45, 95% CI:1.33, 4.51] and incident depressive symptoms [Hazard Ratio (HR):1.26, 95% CI:1.00, 1.58]. Three depressive symptom trajectory patterns were identified from growth mixture models: low, moderate increasing, and borderline high depressive symptom levels. Those with moderate or greater HL were more likely to be in the borderline high depressive-symptom trajectory class than the low trajectory class [Relative Risk Ratio (RRR):1.16, 95% CI:1.01, 1.32]. CONCLUSIONS: HL was associated with greater depressive symptoms. Although findings were not statistically significantly different by gender and race, estimates were generally stronger for women and Black participants. Investigation of psychosocial factors and amelioration by hearing aid use could have significant benefit for older adults quality of life.

ObjectiveThe objective of the study is was investigate the association between hearing impairment and anxiety.MethodWe conducted a cross-sectional analysis of 1,732 community-based adults aged 76 to 85 years who participated in the Health Aging and Body Composition (ABC) study. Logistic regression models were adjusted for demographic and cardiovascular risk factors. Hearing impairment was defined by the speech-frequency pure tone average. Anxiety was defined as reporting two symptoms of at least "a little" or one symptom "quite a bit" on the three-item Hopkins Symptom Checklist.ResultsCompared with individuals with no hearing impairment, the odds of prevalent anxiety were higher among individuals with mild hearing impairment (odds ratio [OR] = 1.32, 95% confidence interval [CI] = [1.01, 1.73]) and moderate or greater hearing impairment (OR = 1.59, 95% CI = [1.14, 2.22]). Hearing aid use was not significantly associated with lower odds of anxiety.DiscussionHearing impairment is independently associated with greater odds of anxiety symptoms in older adults.

OBJECTIVE: Prior studies indicate that olfactory function may be an early marker for cognitive impairment, but the body of evidence has been largely restricted to white populations. METHODS: We studied 2,428 community-dwelling black and white older adults (baseline age 70-79 years) without dementia enrolled in the Health, Aging, and Body Composition (Health ABC) study. Olfaction was measured as odor identification (OI) with the 12-item Cross Cultural Smell Identification Test in year 3. We defined incident dementia over 12 years on the basis of hospitalization records, prescription for dementia medication, or 1.5-SD decline in race-stratified global cognition score. We assessed dementia risk associated with OI score (by tertile) using Cox proportional hazards models. All analyses were stratified by race. RESULTS: Poorer OI in older adults without dementia was associated with increased risk of dementia. After adjustment for demographics, medical comorbidities, and lifestyle characteristics, white participants in the poor or moderate OI tertile had greater risk of dementia (adjusted hazard ratio [HR] 3.34, 95% confidence interval [CI] 2.45-4.54; and HR 1.84, 95% CI 1.33-2.54, respectively) compared to those in the good tertile of function. Among blacks, worse OI was associated with an increased risk of dementia, but the magnitude of the effect was weaker (p for interaction = 0.04) for the poor OI tertile (adjusted HR 2.03, 95% CI 1.44-2.84) and for the moderate tertile (adjusted HR 1.42, 95% CI 0.97-2.10). There was no interaction between OI and APOE ε4 and risk of dementia. CONCLUSIONS: While the magnitude of the association was stronger in whites, we found that poor OI was associated with increased risk of dementia among both black and white older adults.

BackgroundFew studies have compared the risk of recurrent falls across various antidepressant agents-using detailed dosage and duration data-among community-dwelling older adults, including those who have a history of a fall/fracture.ObjectiveTo examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders.MethodsThis was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection.ResultsUsing multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63).ConclusionAntidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.

ImportanceDepression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.ObjectiveTo investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.Design, setting, and participantsThis was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.Main outcomes and measuresIncident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).ResultsThe analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2% [n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.Conclusions and relevanceOlder adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.

ObjectivesTo better understand the potential impact of hearing impairment (HI) and hearing aid use on emotional vitality and mental health in older adults.MethodWe investigated the cross-sectional association of HI with emotional vitality in 1,903 adults aged 76-85 years in the Health ABC study adjusted for demographic and cardiovascular risk factors. Hearing was defined by the speech frequency pure tone average (no impairment < 25 dB, mild impairment 25-40 dB, and moderate or greater impairment > 40 dB). Emotional vitality was defined as having a high sense of personal mastery, happiness, low depressive symptomatology, and low anxiety.ResultsCompared with individuals with no HI, participants with moderate or greater HI had a 23% lower odds of emotional vitality (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.59-0.99). Hearing aid use was not associated with better emotional vitality (OR = 0.98; 95% CI: 0.81-1.20).DiscussionHI is associated with lower odds of emotional vitality in older adults. Further studies are needed to examine the longitudinal impact of HI on mental health and well-being.

BackgroundDepression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality.MethodsResponses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates.ResultsThree trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk.ConclusionsTrajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care.

BackgroundCross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598).MethodsDepressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH)D was measured at 1-year follow-up and categorized as

BackgroundLow literacy is common among the elderly and possibly more reflective of educational attainment than years of school completed. We examined the association between literacy and risk of likely dementia in older adults.MethodsParticipants were 2,458 black and white elders (aged 71-82) from the Health, Aging and Body Composition study, who completed the Rapid Estimate of Adult Literacy in Medicine and were followed for 8 years. Participants were free of dementia at baseline; incidence of likely dementia was defined by hospital records, prescription for dementia medication, or decline in Modified Mini-Mental State Examination score. We conducted Cox proportional hazard models to evaluate the association between literacy and incidence of likely dementia. Demographics, education, income, comorbidities, lifestyle variables, and apolipoprotein E (APOE) ε4 status were included in adjusted analyses.ResultsTwenty-three percent of participants had limited literacy (

Objective: To evaluate response to anti‐calcitonin gene–related peptide (CGRP) migraine preventives in a real‐world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response. Background: Erenumab‐aooeb, fremanezumab‐vrfm, and galcanezumab‐gnlm target CGRP or its receptor; however, many patients are non‐responsive. Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti‐CGRP migraine preventive between May 2018 and May 2021. Screening of 558 patients identified 289 with data at baseline and first follow‐up visits; data were available for 161 patients at a second follow‐up visit. The primary outcome was migraine days per month (MDM). In 198 genotyped patients, we evaluated associations between responders (i.e., patients with ≥50% reduction in MDM at follow‐up) and genes involved in CGRP signaling or pharmacological response, and genetic and polygenic risk scores. Results: The median time to first follow‐up was 4.4 (0.9–22) months after preventive start. At the second follow‐up, 5.7 (0.9–13) months later, 145 patients had continued on the same preventive. Preventives had strong, persistent effects in reducing MDM in responders (follow‐up 1: η2 = 0.26, follow‐up 2: η2 = 0.22). At the first but not second follow‐up: galcanezumab had a larger effect than erenumab, while no difference was seen at either follow‐up between galcanezumab and fremanezumab or fremanezumab and erenumab. The decrease in MDM at follow‐up was generally proportional to baseline MDM, larger in females, and increased with months on medication. At the first follow‐up only, patients with prior hospitalization for migraine or who had not responded to more preventive regimens had a smaller decrease in MDM. Reasons for stopping or switching a preventive varied between medications and were often related to cost and insurance coverage. At both follow‐ups, patient tolerance (1: 92.2% [262/284]; 2: 95.2% [141/145]) and continued use (1: 77.5% [224/289]; 2: 80.6% [116/145]) were high and similar across preventives. Response consistency (always non‐responders: 31.7% [46/145]; always responders: 56.5% [82/145], and one‐time only responders: 11.7% [17/145]) was also similar across preventives. Non‐responder status had nominally significant associations with rs12615320‐G in RAMP1 (odds ratio [95% confidence interval]: 4.7 [1.5, 14.7]), and rs4680‐A in COMT (0.6[0.4, 0.9]). Non‐responders had a lower mean genetic risk score than responders (1.0 vs. 1.1; t(df) = −1.75(174.84), p = 0.041), and the fraction of responders increased with genetic and polygenic risk score percentile. Conclusions: In this real‐world setting, anti‐CGRP preventives reduced MDM persistently and had similar and large effect sizes on MDM reduction; however, clinical and genetic factors influenced response. [ABSTRACT FROM AUTHOR]

This article discusses the implementation of a diversity, equity, and inclusion (DEI) curriculum for health research professionals at a large academic research institution. The curriculum consisted of four workshops aimed at increasing knowledge of core DEI concepts and improving skills for inclusive behaviors. Attendees showed increased DEI knowledge and perceived skills throughout the sessions. The curriculum was developed based on a needs assessment survey and feedback from department members. The workshops focused on topics such as unconscious bias, cultural humility, microaggressions, and allyship. The article emphasizes the importance of diversity and inclusion in the fields of public health and health sciences. [Extracted from the article]

BACKGROUND Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. METHODOLOGY/PRINCIPAL FINDINGS To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL.BACKGROUND Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. METHODOLOGY/PRINCIPAL FINDINGS To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. CONCLUSIONS Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.

BackgroundMany factors contribute to mortality in older women, but their relative importance and independent contribution have been poorly characterized.MethodsFrom 1990 to 1992, we assessed demographics, lifestyle measures, prevalent disease, medication use, anthropometrics, vital signs, and physical function in 17 748 postmenopausal women. We used proportional hazards modeling to evaluate their association with mortality.ResultsDuring 9 years of follow-up, 1886 women (10.6%) died. The relative hazard (RH) of death was approximately 1.5 (95% confidence interval [CI], 1.5-1.6) per 5 years of age, 1.4 (95% CI, 1.2-1.6) for a history of heart disease, and 1.9 (95% CI, 1.6-2.3) for a history of breast cancer. Modifiable risk factors associated with mortality included smoking (RH, 3.7 [95% CI, 3.1-4.5] for current smokers with a > or =50 pack-year history) and systolic blood pressure (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile). Elevated waist-hip ratio was associated with higher mortality (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile), but obesity was associated with lower mortality (RH, 0.7 [95% CI, 0.6-0.9] for body mass index [calculated as weight in kilograms divided by the square of height in meters] of >35.0 vs 18.5-25.0). Poor results on the timed Up and Go Test, a measure of physical function, were also strongly associated with mortality (RH, 1.7 [95% CI, 1.4-2.0], fifth vs first quintile).ConclusionsSimple measures are sufficient to stratify postmenopausal women into groups at high and low risk of dying. Smoking, central obesity, blood pressure, and physical function are potentially modifiable risk factors, although clinical trials are required to demonstrate that change in these factors affects mortality.

ObjectivesThe purpose of this study is to describe the early study medication discontinuation (SMD) experience during the first year of follow-up in a randomized clinical trial in older women and to determine the associations between various baseline characteristics and risk of SMD. DESIGH, SETTING, AND PARTICIPANTS: The authors studied 6,459 postmenopausal women aged 55 to 80 from 11 clinical settings during their first year of participation in the Fracture Intervention Trial (FIT). This trial was designed to test the efficacy of alendronate (Fosamax) on fracture prevention among women with low bone mass.ResultsStudy medication discontinuation was greatest in the first month post-randomization (2.2%) and declined thereafter. Cumulative rates of study medication discontinuation were 4.8% (n = 311) at 3 months and 11.1% (n = 717) at 12 months. SMD was not associated with age, marital status, alcohol consumption, regular exercise, past estrogen replacement therapy use, bone mineral density, or personal or maternal fracture history. After adjusting for covariates and markers of comorbidity, the strongest predictor of SMD was fair-to-poor self-rated health (relative risk (RR) 2.10; 95% confidence interval (CI) 1.47, 2.99). Having four or more depressive symptoms was also a significant predictor and had a risk associated with SMD (RR vs none 1.34; 95% CI 1.05, 1.71) similar to that seen for individuals with good self-rated health (RR 1.49; 95% CI 1.16, 1.91).ConclusionsResults from this cohort emphasize that clinical trials in older women with multiple concomitant conditions can achieve high levels of adherence. Thought should be given to measuring self-rated health and depressive symptoms before randomization to help identify individuals to be targeted for special assistance programs that focus on encouraging adherence.

ContextAlendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures.ObjectiveTo test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures.DesignRandomized, blinded, placebo-controlled trial.SettingEleven community-based clinical research centers.SubjectsWomen aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).InterventionAll participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.Main outcome measuresClinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry.ResultsAlendronate increased BMD at all sites studied (P2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects.ConclusionsIn women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.