Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

CONTEXT: While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. OBJECTIVE: We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. METHODS: Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. RESULTS: Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. CONCLUSION: A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

Associations of Age at Menopause With Postmenopausal Bone Mineral Density and Fracture Risk in Women.

CONTEXT: Menopause before age 45 is a risk factor for fractures, but menopause occurs at age ≥45 in ~90% of women. OBJECTIVE: To determine, in women with menopause at age ≥45, whether (1) years since the final menstrual period (FMP) is more strongly associated with postmenopausal bone mineral density (BMD) than chronological age and (2) lower age at FMP is related to more fractures. DESIGN AND SETTING: The Study of Women's Health Across the Nation, a longitudinal cohort study of the menopause transition (MT). PARTICIPANTS: A diverse cohort of ambulatory women (pre- or early perimenopausal at baseline, with 15 near-annual follow-up assessments). MAIN OUTCOME MEASURES: Postmenopausal lumbar spine (LS) or femoral neck (FN) BMD (n = 1038) and time to fracture (n = 1554). RESULTS: Adjusted for age, body mass index (BMI), cigarette use, alcohol intake, baseline LS or FN BMD, baseline MT stage, and study site using multivariable linear regression, each additional year after the FMP was associated with 0.006 g/cm2 (P < 0.0001) and 0.004 g/cm2 (P < 0.0001) lower postmenopausal LS and FN BMD, respectively. Age was not related to FN BMD independent of years since FMP. In Cox proportional hazards regression, accounting for race/ethnicity, BMI, cigarette use, alcohol intake, prior fracture, diabetes status, exposure to bone-modifying medications/supplements, and study site, the hazard for incident fracture was 5% greater for each 1-year decrement in age at FMP (P = 0.02). CONCLUSIONS: Years since the FMP is more strongly associated with postmenopausal BMD than chronological age, and earlier menopause is associated with more fractures.

Faster Lumbar Spine Bone Loss in Midlife Predicts Subsequent Fracture Independent of Starting Bone Mineral Density.

CONTEXT: Bone mineral density (BMD) decreases rapidly during menopause transition (MT), and continues to decline in postmenopause. OBJECTIVE: This work aims to examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. METHODS: The Study of Women's Health Across the Nation, a longitudinal cohort study, included 451 women, initially premenopausal or early perimenopausal, and those transitioned to postmenopause. Main outcome measures included time to first fracture after early postmenopause. RESULTS: In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone-detrimental or -beneficial medications, each SD decrement in lumbar spine (LS) BMD before MT was associated with a 78% increment in fracture hazard (P = .007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (P = .04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and an LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (P = .03). At the femoral neck, neither starting BMD nor rate of BMD decline was associated with fracture. CONCLUSION: At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with a below-median starting LS BMD and a faster-than-median LS BMD decline have the greatest fracture risk.

Temporal increases in 25-hydroxyvitamin D in midlife women: Longitudinal results from the Study of Women's Health Across the Nation.

OBJECTIVE: 25-hydroxyvitamin D (25(OH)D) is critical for bone mineralization and may prevent fractures. Understanding vitamin D deficiency trends in midlife women is particularly important given their concurrent menopausal changes that increase risk for fracture. We aimed to evaluate changes in mean 25(OH)D over time and their determinants in a racially, ethnically and socioeconomically diverse cohort of midlife women. DESIGN: A multi-centre prospective cohort study. PATIENTS: 1585 women ages 42-52 years at baseline. MEASUREMENTS: We measured serum 25(OH)D at 2 time points (1998-2000 and 2009-2011). Between-visit change was assessed in the whole cohort and in socioeconomic and demographic subgroups. Among those with vitamin D deficiency (25(OH)D <30 nmol/L) at baseline, we evaluated determinants of persistent deficiency at follow-up. RESULTS: Mean 25(OH)D increased from 53.8 to 70.0 nmol/L (P < 0.001), and the prevalence of deficiency decreased from 20.4% to 9.7% (P < 0.001). While baseline 25(OH)D differed among subgroups, the changes in 25(OH)D were similar among groups. The proportion of women reporting dietary supplement use increased from 40.8% to 67.1% (P < 0.001), and the increase in 25(OH)D was significantly higher in supplement users. Among women with vitamin D deficiency at baseline, White women and supplement users were less likely to remain deficient at follow-up. CONCLUSIONS: Among midlife women, temporal increases in 25(OH)D concentrations are driven largely by increases in supplement use. The proportion of women with 25(OH)D <30 nmol/L and thus at high risk for skeletal consequences remains substantial. Targeted screening for vitamin D deficiency in populations at risk for fragility fracture may be advisable.

Physician-patient communication about dietary supplements.

OBJECTIVE: Describe the content and frequency of provider-patient dietary supplement discussions during primary care office visits. METHODS: Inductive content analysis of 1477 transcribed audio-recorded office visits to 102 primary care providers was combined with patient and provider surveys. Encounters were collected in Los Angeles, CA (2009-2010), geographically diverse practice settings across the United States (2004-2005), and Sacramento, CA (1998-1999). RESULTS: Providers discussed 738 dietary supplements during encounters with 357 patients (24.2% of all encounters in the data). They mentioned: (1) reason for taking the supplement for 46.5% of dietary supplements; (2) how to take the supplement for 28.2%; (3) potential risks for 17.3%; (4) supplement effectiveness for 16.7%; and (5) supplement cost or affordability for 4.2%. Of these five topics, a mean of 1.13 (SD=1.2) topics were discussed for each supplement. More topics were reviewed for non-vitamin non-mineral supplements (mean 1.47 (SD=1.2)) than for vitamin/mineral supplements (mean 0.99 (SD=1.1); p<0.001). CONCLUSION: While discussions about supplements are occurring, it is clear that more discussion might be needed to inform patient decisions about supplement use. PRACTICE IMPLICATIONS: Physicians could more frequently address topics that may influence patient dietary supplement use, such as the risks, effectiveness, and costs of supplements.

Dietary phytoestrogen intakes and cognitive function during the menopausal transition: results from the Study of Women's Health Across the Nation Phytoestrogen Study.

OBJECTIVE: Phytoestrogens, which consist mainly of isoflavones, lignans, and coumestans have estrogenic and anti-inflammatory properties. Previous research suggests that higher dietary or supplemental intakes of isoflavones and lignans are related to better cognitive performance in middle-aged and older women. METHODS: We conducted longitudinal analysis of dietary phytoestrogens and cognitive performance in a cohort of African American, white, Chinese, and Japanese women undergoing the menopausal transition. The tests were Symbol Digit Modalities, East Boston Memory, and Digits Span Backward. Phytoestrogens were assessed using the Food Frequency Questionnaire. We modeled each cognitive score as a function of concurrent value of the primary predictors (highest tertile of isoflavones, lignans, or coumestrol) and covariates including the menopausal transition stage. RESULTS: Coumestrol and isoflavone intakes were 10 and 25 times greater, respectively, in Asian than in non-Asian participants. During late perimenopause and postmenopause, Asian women with high isoflavone intakes did better on processing speed, but during early perimenopause and postmenopause, high-isoflavone Asian consumers performed worse on verbal memory. The highest isoflavone consumers among non-Asians likewise posted lower verbal memory scores during early perimenopause. A verbal memory benefit of higher dietary lignan consumption was apparent only during late perimenopause, when women from all ethnic/racial groups who were in the highest tertile of intake demonstrated a small advantage. Coumestrol was unrelated to cognitive performance. CONCLUSIONS: The cognitive effects of dietary phytoestrogens are small, seem to be class-specific, vary by menopause stage and cognitive domain, and differ among ethnic/racial groups (but whether this is related to dose or to host factors cannot be discerned).

Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study.

CONTEXT: Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. OBJECTIVE: The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. DESIGN: This was a cross-sectional analysis. SETTING AND PARTICIPANTS: The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. OUTCOME MEASUREMENTS: Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. RESULTS: Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [-0.20 sd, 95% CI (-0.38, -0.03) sd for compression, -0.19 sd, 95% CI (-0.38, -0.003) sd for bending, -0.19 sd, 95% CI (-0.37, -0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. CONCLUSIONS: Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes.

Yoga decreases kyphosis in senior women and men with adult-onset hyperkyphosis: results of a randomized controlled trial.

OBJECTIVES: To assess whether a specifically designed yoga intervention can reduce hyperkyphosis. DESIGN: A 6-month, two-group, randomized, controlled, single-masked trial. SETTING: Community research unit. PARTICIPANTS: One hundred eighteen women and men aged 60 and older with a kyphosis angle of 40 degrees or greater. Major exclusions were serious medical comorbidity, use of assistive device, inability to hear or see adequately for participation, and inability to pass a physical safety screen. INTERVENTION: The active treatment group attended hour-long yoga classes 3 days per week for 24 weeks. The control group attended a monthly luncheon and seminar and received mailings. MEASUREMENTS: Primary outcomes were change (baseline to 6 months) in Debrunner kyphometer-assessed kyphosis angle, standing height, timed chair stands, functional reach, and walking speed. Secondary outcomes were change in kyphosis index, flexicurve kyphosis angle, Rancho Bernardo Blocks posture assessment, and health-related quality of life (HRQOL). RESULTS: Compared with control participants, participants randomized to yoga experienced a 4.4% improvement in flexicurve kyphosis angle (P=.006) and a 5% improvement in kyphosis index (P=.004). The intervention did not result in statistically significant improvement in Debrunner kyphometer angle, measured physical performance, or self-assessed HRQOL (each P>.1). CONCLUSION: The decrease in flexicurve kyphosis angle in the yoga treatment group shows that hyperkyphosis is remediable, a critical first step in the pathway to treating or preventing this condition. Larger, more-definitive studies of yoga or other interventions for hyperkyphosis should be considered. Targeting individuals with more-malleable spines and using longitudinally precise measures of kyphosis could strengthen the treatment effect.

Moderate alcohol consumption and safety of lovastatin and warfarin among men: the post-coronary artery bypass graft trial.

PURPOSE: Although moderate drinking has been associated with lower mortality among patients with coronary heart disease, its safety among patients taking common cardiac medications is unknown. SUBJECTS AND METHODS: We studied 1244 men enrolled in the Post-Coronary Artery Bypass Graft (CABG) Trial who had undergone previous coronary bypass surgery. Participants were randomly assigned to lovastatin in low (mean 4 mg) or high (mean 76 mg) doses and to low-dose warfarin (mean international normalized ratio [INR] 1.4, goal INR <2.0) or placebo in a factorial design. Participants underwent routine measurement of alanine aminotransferase (ALT) and INR levels every 6 to 12 weeks for 4 to 5 years. We categorized weekly alcohol intake as abstention (<1 drink), light (1-6 drinks), moderate (7-13 drinks), and heavier (> or =14 drinks). RESULTS: During follow-up, 66% of men taking warfarin had an INR of 2.0 or higher, and 7% of men had an ALT of 80 IU/L or higher. Maximum INR (P = .72) and ALT (P = .51) levels did not differ across categories of alcohol intake. The risks of an INR of 2.0 or higher were 67%, 66%, 68%, and 61% among non-, light, moderate, and heavier drinkers (P = .86), respectively. The corresponding risks of an ALT of 80 IU/L or more were 8%, 10%, 9%, and 6% (P = .70), respectively. CONCLUSION: Moderate drinking did not adversely influence the safety of low-dose warfarin or even high-dose lovastatin among men in this randomized trial, as measured by INR and ALT levels.