Renal function and nonvertebral fracture risk in multiethnic women: the Women’s Health Initiative (WHI)

Summary

To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women??s Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

Introduction

The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups.

Methods

A nested case?Ccontrol study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR_cys-c).

Results

Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04?C1.46). The OR of fracture was 1.16 (95% CI, 0.85?C1.58) among women with eGFR_cys-c 60?C90?mL/min/1.73m² and 2.46 (95% CI, 1.16?C5.21) among those with eGFR_cys-c <60?mL/min/1.73m² compared to the reference group (eGFR_cys-c >90?mL/min/1.73m²) (p trend?=?0.05). The association was reduced after adjustment for cytokine TNF?? soluble receptors (OR, 1.62; 95% CI, 0.59?C4.46 for eGFR_cys-c <60?mL/min/1.73?m²). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00?C1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women.

Conclusion

Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.     

Socioeconomic status in relation to incident fracture risk in the Study of Women’s Health Across the Nation

Summary

We examined baseline and annual follow-up data (through annual follow-up visit 9) from a cohort of 2,234 women aged 42 to 52 years at baseline. Independent of financial status, higher educational level was associated with lower fracture incidence among non-Caucasian women but not among Caucasian women.

Introduction

This study was conducted to determine the associations of education and income with fracture incidence among midlife women over 9 years of follow-up.

Methods

We examined baseline and annual follow-up data (through annual follow-up visit 9) from 2,234 participants of the Study of Women’s Health Across the Nation, a cohort of women aged 42 to 52 years at baseline. We used Cox proportional hazards regression models to examine the associations of socioeconomic predictors (education, family-adjusted poverty-to-income ratio, and difficulty paying for basics) with time to first incident nontraumatic, nondigital, noncraniofacial fracture.

Results

Independent of family-adjusted poverty-to-income ratio, higher educational level was associated with decreased time to first incident fracture among non-Caucasian women but not among Caucasian women (p _interaction 0.02). Compared with non-Caucasian women who completed no more than high school education, non-Caucasian women who attained at least some postgraduate education had 87 % lower rates of incident nontraumatic fracture (adjusted hazard ratio 0.13, 95 % confidence interval [CI] 0.03–0.60). Among non-Caucasian women, each additional year of education was associated with a 16 % lower odds of nontraumatic fracture (adjusted odds ratio 0.84, 95 % CI 0.73–0.97). Income, family-adjusted poverty-to-income ratio, and degree of difficulty paying for basic needs were not associated with time to first fracture in Caucasian or non-Caucasian women.

Conclusions

Among non-Caucasian midlife women, higher education, but not higher income, was associated with lower fracture incidence. Elucidation of the mechanisms underlying the possible protective effects of higher educational level on nontraumatic fracture incidence may allow us to better target individuals at risk of future fracture.     

Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women’s Health Initiative

Summary  Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk. Introduction  Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases. Methods  In this study, postmenopausal women (N = 146,959) from the Women’s Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model. Results  While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13–2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65–2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06–1.25) or OC diagnosis (HR = 1.27, CI = 1.18–1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05). Conclusions  Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.     

Abdominal obesity and hip fracture: results from the Nurses’ Health Study and the Health Professionals Follow-up Study

Summary

Abdominal obesity might increase fracture risk. We studied the prospective associations between waist circumference, waist-to-hip ratio, and hip fracture. The indicators of abdominal obesity were associated with increased hip fracture risk in women, but not in men. The increased risk was restricted to women with low physical activity.

Introduction

Low weight is an established risk factor for osteoporosis and hip fracture. However, the association between fat tissue, muscle, and bone is complex, and abdominal obesity might increase fracture risk. We studied the prospective associations between indicators of abdominal obesity and hip fracture in two large US cohorts.

Methods

At baseline in 1986 and through biennial follow-up, information on hip fracture and potential risk factors was collected in 61,677 postmenopausal women and 35,488 men above age 50. Waist and hip circumferences were reported at baseline and updated twice.

Results

During follow-up, 1168 women and 483 men sustained a hip fracture. After controlling for known risk factors, there was a significant association in women between increasing waist circumference and hip fracture (RR per 10-cm increase 1.13 (95 % CI 1.04–1.23) and between increasing waist-to-hip ratio and hip fracture (RR per 0.1 unit increase 1.14 (95 % CI 1.04–1.23), but these associations were not seen in men. In women, both measures interacted with physical activity. Those in the highest (≥0.90) versus lowest (<0.75) category of waist-to-hip ratio had increased risk of hip fracture if their activity was less than the population median (RR?=?1.61, 95 % CI 1.18–2.19) but not if their activity was higher (RR?=?1.00, 95 % CI 0.72–1.40). A similar pattern was found for waist circumference.

Conclusion

Indicators of abdominal obesity were associated with increased hip fracture risk after controlling for BMI in women. The increased risk was restricted to women with low physical activity. In men, no significant associations were found.

     

Design of the POSSIBLE US™ Study: postmenopausal women’s compliance and persistence with osteoporosis medications

Summary  Failure to take prescribed medication is common. The POSSIBLE US™ study is evaluating the impact of physician and patient characteristics on patient-reported compliance and persistence with osteoporosis medications. We report our study design and the baseline characteristics of 4,994 postmenopausal women recruited from primary care physician offices in 33 states. Introduction  The Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™) is a longitudinal cohort study of osteoporosis therapy in primary care. Methods  Between 2004 and 2007, 134 physicians (in 33 states) enrolled postmenopausal women initiating, changing, or continuing osteoporosis medications. After completing a baseline questionnaire, participants will provide data semi-annually for up to 3 years through 2008. Physicians provide patient data at baseline and routine follow-up visits. Participants from 23 sites also signed a release regarding administrative claims data for economic analyses and validation of self-reported data. Baseline results  Four thousand nine hundred and ninety-four evaluable women were recruited from internal medicine (n = 1,784), family practice (n = 1,556), obstetrics/gynecology (n = 1,556), and from one rheumatology practice (n = 98). Mean participant age was 64.3 years (SD = 9.97); 89% were Caucasian; 59% had some college education. Sixty-three percent used a single osteoporosis agent, usually a bisphosphonate. For monotherapy patients, concordance between clinic- and patient-reported medication use was lowest for patients prescribed estrogen therapy (70%) or calcium/vitamin D (72%). Obstetrician/gynecologists enrolled younger women, who were more likely to use estrogen therapy than patients enrolled by other physicians. The 934 women (19%) prescribed only calcium/vitamin D were younger than women prescribed pharmacologic therapy. Conclusions  POSSIBLE US™ provides a unique foundation for evaluating longitudinal use of osteoporosis medications and related outcomes.     

Failure to perceive increased risk of fracture in women 55?years and older: the Global Longitudinal Study of Osteoporosis in Women (GLOW)

Summary

We compared self-perception of fracture risk with actual risk among 60,393 postmenopausal women aged ??55?years, using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. Improved education about osteoporosis risk factors is needed.

Introduction

This study seeks to compare self-perception of fracture risk with actual risk among postmenopausal women using data from GLOW.

Methods

GLOW is an international, observational, cohort study involving 723 physician practices in 17 sites in ten countries in Europe, North America, and Australia. Participants included 60,393 women ??55?years attended by their physician during the previous 24?months. The sample was enriched so that two thirds were ??65?years. Baseline surveys were mailed October 2006 to February 2008. Main outcome measures were self-perception of fracture risk in women with elevated risk vs women of the same age and frequency of risk factors for fragility fracture.

Results

In the overall study population, 19% (10,951/58,434) of women rated their risk of fracture as a little/much higher than that of women of the same age; 46% (27,138/58,434) said it was similar; 35% (20,345/58,434) believed it to be a little/much lower. Among women whose actual risk was increased based on the presence of any one of seven risk factors for fracture, the proportion who recognized their increased risk ranged from 19% for smokers to 39% for current users of glucocorticoid medication. Only 33% (4,185/12,612) of those with ??2 risk factors perceived themselves as being at higher risk. Among women reporting a diagnosis of osteopenia or osteoporosis, only 25% and 43%, respectively, thought their risk was increased.

Conclusion

In this international, observational study, most postmenopausal women with risk factors failed to appreciate their actual risk for fracture.     

Impact of diabetes mellitus and cardiometabolic syndrome on the risk of Alzheimer’s disease among postmenopausal women

BACKGROUNDIn spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer’s disease (AD) in the aging population worldwide, limited attention has been paid to their potential association.AIMTo investigate the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women.METHODSPostmenopausal women aged 50-79 (n = 63117) who participated in the U.S. Women’s Health Initiative Observational Study (WHIOS), recruited in 1993-1998, without baseline AD and followed up through March 1, 2019, were analyzed. AD was classified by participant-reported history of doctor-diagnosis of incident AD in the WHIOS. DM was defined by participant-report or treated because of diabetes or serum glucose concentrations ≥ 126 mg/dL. CMS was defined as having ≥ 3 of five CMS components: large waist circumference, high blood pressure, elevated triglycerides, elevated glucose, and low high-density lipoprotein cholesterol. The associations of DM and CMS with AD were analyzed using Cox’s proportional hazards regression analysis.RESULTSDuring a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 developed incident AD. Women with DM had significantly higher incidence of AD [8.5, 95% confidence interval (CI): 8.0-9.0 per 1000 person-years (PY)] than those without DM (7.1, 95%CI: 6.9-7.2 per 1000 PY). Multivariate Cox’s regression analysis indicated that women with DM or CMS had a significantly higher risk of AD than those without DM or CMS. The corresponding hazard ratios [HR (95%CI)] were 1.22 (1.13-1.31, P < 0.001) in subjects with DM, and 1.18 (1.09-1.27, P < 0.001) in subjects with CMS. The HRs diminished with age and became non-significant in the oldest age group.CONCLUSIONDuring a median follow-up of 20 years, DM and CMS were significantly associated with the risk of AD among postmenopausal women. More specifically, women aged 50-69 with DM or CMS vs those without these conditions had significantly higher relative risks of AD than the relative risks of AD in those aged 70-79 with DM or CMS vs those without DM or CMS.     

Do hip protectors decrease the risk of hip fracture in institutional and community-dwelling elderly? A systematic review and meta-analysis of randomized controlled trials

Hip fractures are an important cause of morbidity and mortality in the elderly. Hip protectors are padded undergarments designed to decrease the impact of a fall on the hip. We systematically reviewed randomized controlled trials of hip protectors to determine if they reduce hip fractures in the elderly. Analyses were pooled according to participant residence—community or institutional (the latter, included nursing homes, residential group homes or seniors hostels). We included individually randomized and statistically adjusted cluster randomized trials. Seven trials of 12- to 28-month duration were included. The Safehip brand of hip protector was used in most studies. Compliance rates in the treatment groups varied from 31 to 68%. In four trials including a total of 5,696 community-dwelling seniors, the hip fracture rates in control groups ranged from 1.1 to 7.4%, and the pooled risk difference with hip protector allocation was 0% [95% confidence intervals (CI), –1%, +1%), with a relative risk of 1.07 (0.81, 1.42). In three trials including 1,188 institutionalized elderly participants, hip fracture rates in the control groups varied from 8 to 19.4%, and the pooled risk difference for sustaining one or more hip fractures with hip protector allocation was –3.7% (95% CI, –7.4%, 0.1%), with a relative risk of 0.56 (0.31, 1.01) (with statistically significant heterogeneity of treatment effect). In a post-hoc subgroup analysis of two trials comprised of exclusively nursing home residents, the risk difference with hip protector allocation was –4.4% (–8.09, –0.76) with a relative risk of 0.50 (0.28, 0.91) ( n =1,014). Thus, there is little evidence to support the use of hip protectors outside the nursing home setting. The potential benefit of hip protectors in reducing hip fractures in nursing home residents requires further confirmation.     

A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX?

Summary  

The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability.     

Low dose and short-term therapy of tibolone reduces the cardiovascular disease risk in postmenopausal women

<正>Objective:To investigate the effects of low dose tibolone short-term therapy on clinic, endocrine and markers of cardiovascular disease in healthy postmenopausal women. Methods: A prospective study involved a total of 42 eligible postmenopausal women. 22 cases as group A and 20 cases as group B. Complete baseline work-up including Kupperman score, body mass index (BMI), gonadotropin (FSH, LH) , estrogen (E2), testosterone (T) , sex hormone binding globulin (SHBG), plasminogen activator inhibitor type 1 (PAI-1), tissue plas-minogen activator (tPA), high-sensitivity C-response protein (hs-CRP), nitrogen oxide (NO) and fasting lipid, glucose(FPG) , insulin(FINS) were performed in all subjects. Postmenopausal women in group A were treated with 1. 25 mg tibolone daily. Women in group B were treated with 0. 625 mg tibolone daily. Women both in group A and group B were given calcium 600 mg with vitamin D 125IU per day. At the end of the 12-weeks therapy, subjects were re-evaluated and above parameters were measured. Results: No significant differences between group A and group B were found at baseline. Twenty-eight cases (fourteen cases in each group) completed the study. Kupperman score decreased from (22. 1±8. 0) and (25. 4±7. 5) to (7. 7±4. 5) and (5. 2±4. 5) and plasminogen activator inhibitor type 1 decreased from (95. 8±32. 4)μg/L and (102. 9±42. 6)μg/L to (72. 2±39. 6)μg/L and (79. 9±30. 1)μg/L significantly in group A and group B respectively after treatment. In group A, Blood pressure decreased significantly from (120±10)/(83±6) mmHg to (110±14)/(77±9) mmHg (P<0. 05), testosterone increased significantly from (0. 6±0. 4) nmol/L to (1. 3±1. 1) nmol/L (P<0. 05), free testosterone increased from (0. 001±0. 002) nmol/L to (0. 003±0.003) nmol/L significantly (P<0. 01), SHBG decreased from (7. 6±4. 9) nmol/L to (4. 3±2. 9) nmol/L significantly (P<0. 05) , total cholesterol decreased from (5. 4±0. 8) mmol/L to (5. 0±0. 8) mmol/L significantly (P<0. 01) , ApoA decreased from (1. 8±0. 3) mg/dl to (1. 7±0. 3) mg/dl significantly (P<0. 05) , fasting glucose decreased from (5. 6±0. 8) mmol/L to (3. 9±1. 1) mmol/L significantly (P<0. 01) and no significant differences in BMI, FSH, LH, E2, tPA, hs-CRP, NO, TG, HDL-C, LDL-C, apoB were found after treatment. In group B, there were no significant differences in other parameters found after treatment except Kupperman score and PAI-1. Conclusions: 1. 25 mg/d tibolone short-term therapy was associated with improved fibrinolyt-ic factors and decreased Kupperman score, blood pressure, total cholesterol and fasting blood glucose level. 0. 625 mg/d tibolone therapy resulted in decrease Kupperman score and improvement of fibrinolytic factors. These changes relieve climacteric symptoms and may have some benefits on preventing the development of cardiovascular disease. An increased testosterone and free testosterone levels in 1. 25 mg dose of tibolone therapy may increase energy level, general well-being and sexual desire in postmenopausal women. Low dose tibolone replacement therapy is a convenient effective HRT for postmenopausal women     

The Women’s Health Initiative: Hormone Therapy and Calcium/Vitamin D Supplementation Trials

The Women’s Health Initiative (WHI) was a large and complex study focused on strategies for the prevention and control of common chronic diseases of postmenopausal women. The WHI included 3 randomized controlled trials: the Hormone Therapy (HT) Trials, the Diet Modification Trial, and the Calcium/Vitamin D (CaD) Trial. Conjugated equine estrogen with or without a progestin significantly decreased hip, clinical vertebral, and all fractures. Once the intervention was stopped, the fracture benefit dissipated. However, estrogen plus progestin was associated with more risks than benefits and use of hormone therapy solely for the prevention of osteoporosis is not recommended. The CaD trial found no overall benefit for fracture reduction except in adherent women and women taking supplements for 5 or more years. Overall, the common practice of taking calcium and vitamin D supplementation with possible benefits on hip and positive evidence on bone mineral density and few risks is reasonable.     

Severity of vertebral fracture and risk of hip fracture: a nested case�Ccontrol study

Summary  

Severe vertebral fractures strongly predicted subsequent hip fracture in this population-based study. Such high-risk patients should be provided with clinical evaluation and care for osteoporosis.     

Hip structural geometry and incidence of hip fracture in postmenopausal women: what does it add to conventional bone mineral density?

Summary

Hip geometry measurements of outer diameter and buckling ratio at the intertrochanter and shaft of the hip dual energy X-ray absorptiometry (DXA) scan predicted incident hip fracture in postmenopausal women. These associations, independent of age, body size, clinical risk factors, and conventional areal bone mineral density, suggest hip geometry plays a role in fracture etiology and may aid in improving identification of older women at high fracture risk.

Introduction

This study examined whether hip geometry parameters predicted hip fracture independent of body size, clinical risk factors, and conventional femoral neck bone mineral density (aBMD) and whether summary factors could be identified to predict hip fracture.

Methods

We studied 10,290 postmenopausal women from the Women's Health Initiative. Eight thousand eight hundred forty-three remained fracture free during follow-up to 11 years of follow-up, while 147 fractured their hip, and 1,300 had other clinical fractures. Hip structural analysis software measured bone cross-sectional area, outer diameter, section modulus, average cortical thickness, and buckling ratio on archived DXA scans in three hip regions: narrow neck, intertrochanter, and shaft. Hazard ratios were estimated using Cox proportional hazards models for individual parameters and for composite factors extracted from principal components analysis from all 15 parameters.

Results

After adjustment for age, body size, clinical risk factors, and aBMD, intertrochanter and shaft outer diameter measurements remained independent predictors of hip fracture with hazard ratios for a one standard deviation increase of 1.61 (95% confidence interval (CI), 1.25–2.08) for the intertrochanter and 1.36 (95% CI, 1.06–1.76) for the shaft. Average buckling ratios also independently predicted incident hip fracture with hazard ratios of 1.43 (95% CI, 1.10–1.87) at the intertrochanter and 1.24 (95% CI, 1.00–1.55) at the shaft. Although two composite factors were extracted from principal components analysis, neither was superior to these individual measurements at predicting incident hip fracture.

Conclusions

Two hip geometry parameters, intertrochanter outer diameter and buckling ratio, predict incident hip fracture after accounting for clinical risk factors and aBMD.