Early time-restricted eating affects weight, metabolic health, mood, and sleep in adherent completers: A secondary analysis.

OBJECTIVE: Data are mixed on whether intermittent fasting improves weight loss and cardiometabolic health. Here, the effects of time-restricted eating (TRE) in participants who consistently adhered ≥5 d/wk every week were analyzed. METHODS: Ninety patients aged 25 to 75 years old with obesity were randomized to early TRE (eTRE; 8-hour eating window from 07:00 to 15:00) or a control schedule (≥12-hour window) for 14 weeks. A per-protocol analysis of weight loss, body composition, cardiometabolic health, and other end points was performed. RESULTS: Participants who adhered to eTRE ≥5 d/wk every week had greater improvements in body weight (-3.7 ± 1.2 kg; p = 0.003), body fat (-2.8 ± 1.3 kg; p = 0.04), heart rate (-7 ± 3 beats/min; p = 0.02), insulin resistance (-2.80 ± 1.36; p = 0.047), and glucose (-9 ± 5 mg/dL; p = 0.047) relative to adherers in the control group. They also experienced greater improvements in mood, including fatigue and anger; however, they self-reported sleeping less and taking longer to fall asleep. CONCLUSIONS: For those who can consistently adhere at least 5 d/wk, eTRE is a valuable approach for improving body weight, body fat, cardiometabolic health, and mood. Further research is needed to determine whether eTRE's effects of shortening sleep but reducing fatigue are healthful or not.

Impact of early time-restricted eating on diet quality, meal frequency, appetite, and eating behaviors: A randomized trial.

OBJECTIVE: Time-restricted eating (TRE) can reduce body weight, but it is unclear how it influences dietary patterns and behavior. Therefore, this study assessed the effects of TRE on diet quality, appetite, and several eating behaviors. METHODS: Adults with obesity were randomized to early TRE plus energy restriction (eTRE + ER; 8-hour eating window from 7:00 a.m. to 3:00 p.m.) or a control eating schedule plus energy restriction (CON + ER; ≥12-hour window) for 14 weeks. Food intake was assessed via the Remote Food Photography Method, while eating patterns, appetite, and eating behaviors were assessed via questionnaires. RESULTS: A total of 59 participants completed the trial, of whom 45 had valid food records. eTRE + ER did not affect eating frequency, eating restraint, emotional eating, or the consistency of mealtimes relative to CON + ER. eTRE + ER also did not affect overall diet quality. The intensity and frequency of hunger and fullness were similar between groups, although the eTRE + ER group was hungrier while fasting. CONCLUSIONS: When combined with a weight-loss program, eTRE does not affect diet quality, meal frequency, eating restraint, emotional eating, or other eating behaviors relative to eating over more than a 12-hour window. Rather, participants implement eTRE as a simple timing rule by condensing their normal eating patterns into a smaller eating window.

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial.

Importance: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. Objective: To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours. Design, Setting, and Participants: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. Interventions: All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window). Main Outcomes and Measures: The co-primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. Results: Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43 [11] years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER. Conclusions and Relevance: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03459703.

Understanding Physicians' Perceptions of Patient-Identified Barriers to Osteoporosis Medication Initiation: A Cognitive Mapping Approach.

Objective: Interventions to initiate medication and increase adherence for postmenopausal women who have had a fragility fracture were not always successful. The purpose of this study was to derive an empirical framework for patient-identified barriers to osteoporosis medication initiation and adherence from physician experts. Methods: A cognitive mapping approach involving nominal group technique (NGT) meetings and a card sorting and rating task were used to obtain formative data. We first conducted four NGT meetings with 18 women patients who were not on osteoporosis treatment to identify barriers to osteoporosis medication, then invited 27 osteoporosis physicians to sort and rate 25 patients identified barriers. Descriptive analysis, multidimensional scaling analysis, and hierarchical cluster analysis were applied for data analysis. Results: A two-dimensional five-cluster cognitive map was derived to provide an organizational framework for understanding patients perceived barriers to medication initiation and adherence. The five clusters were concerns about side effects, experience of side effects, lifestyle changes, medication access and complexity, and patient uncertainty about treatment and trust in the provider. The two dimensions were interpreted as internal to patients (X-axis) and external to patients (Y-axis). Conclusions/Implications: Views of patients solicited in a structured format provided directions to help in designing interventions to improve osteoporosis medication initiation and adherence.

Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting Barriers to Osteoporosis Care: A Randomized Clinical Trial.

Osteoporosis treatment rates are declining, even among those with past fractures. Novel, low-cost approaches are needed to improve osteoporosis care. We conducted a parallel group, controlled, randomized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use. A total of 2684 women with self-reported fracture history after age 45 years not using osteoporosis therapy from US Global Longitudinal Study of Osteoporosis in Women (GLOW) sites were randomized 1:1 to receive a multimodal, tailored, direct-to-patient, video intervention versus usual care. The primary study outcome was self-report of osteoporosis medication use at 6 months. Other outcomes included calcium and vitamin D supplementation, bone mineral density (BMD) testing, readiness for behavioral change, and barriers to treatment. In intent-to-treat analyses, there were no significant differences between groups (intervention versus control) in osteoporosis medication use (11.7% versus 11.4%, p = 0.8), calcium supplementation (31.8% versus 32.6%, p = 0.7), vitamin D intake (41.3% versus 41.9%, p = 0.8), or BMD testing (61.8% versus 57.1%, p = 0.2). In the intervention group, fewer women were in the precontemplative stage of behavior change, more women reported seeing their primary care provider, had concerns regarding osteonecrosis of the jaw, and difficulty in taking/remembering to take osteoporosis medications. We found differences in BMD testing among the subgroup of women with no prior osteoporosis treatment, those who provided contact information, and those with no past BMD testing. In per protocol analyses, women with appreciable exposure to the online intervention (n = 257) were more likely to start nonbisphosphonates (odds ratio [OR] = 2.70; 95% confidence interval [CI] 1.26-5.79) compared with the usual care group. Although our intervention did not increase the use of osteoporosis therapy at 6 months, it increased nonbisphosphonate medication use and BMD testing in select subgroups, shifted participants' readiness for behavior change, and altered perceptions of barriers to osteoporosis treatment. Achieving changes in osteoporosis care using patient activation approaches alone is challenging. © 2018 American Society for Bone and Mineral Research.

A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material.

OBJECTIVE: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake. METHODS: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos. RESULTS: To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not. CONCLUSION: We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.

Pharmacologic approaches to the prevention and management of low bone mineral density in HIV-infected patients.

PURPOSE OF REVIEW: Osteoporosis is a growing concern among people living with HIV (PLWH) because of the recognized risk of fractures, which bring with them morbidity and mortality. New evidence is helping clinicians understand how to prevent and manage osteoporosis in this subpopulation. RECENT FINDINGS: The benefit of calcium and vitamin D is variable in osteoporosis literature in general, but evidence supports the use of these supplements in PLWH to prevent the loss of bone mineral density when initiating antiretroviral therapy and in enhancing the effectiveness of antiosteoporosis treatments. Of the osteoporosis treatments, alendronate and zoledronate are the only two with substantial evidence of safety and effectiveness in PLWH, but the studies have been small and of limited duration. There are no randomized controlled studies of raloxifene, denosumab or teriparatide in PLWH. Of increasing interest is the possible benefit of statins on bone health through decreased inflammation. SUMMARY: Osteoporosis is recognized as an issue for PLWH. Although some of the available osteoporosis treatments have proven safe and effective, future studies of the novel treatments, such as statins, along with well-designed studies of established osteoporosis treatments for use in PLWH are needed to further guide the clinical management of osteoporosis in this population.

Understanding practice-based research participation: The differing motivations of engaged vs. non-engaged clinicians in pragmatic clinical trials.

BACKGROUND/AIMS: Pragmatic clinical trials (PCTs) represent an increasingly used strategy for "real-world" trials. Successful PCTs typically require participation of community-based practices. However, community clinicians often have limited interest or experience in clinical research. Many barriers to practice-based research have been described, but possible motivations to participate among community practices not active in research have not been well explored. The tendency is for researchers to assume similar motivations and priorities across all candidate practices. This is not necessarily the case. A better understanding of the range of reasons clinicians might see for participating in pragmatic trials could be key to promoting this type of practice-based research. METHODS: Semi-structured interviews were conducted with 30 clinicians and staff members. Half of the interviewees had experience doing practice-based clinical trials and half did not. Individuals in these two groups were also diversified in terms of their practice size and location. Participants were asked about motivations and barriers to doing practice-based research in the context of a planned osteoporosis pragmatic clinical trial. Interviews were transcribed, coded, and analyzed. RESULTS: Barriers identified for both experienced and not-experienced clinicians and staff members included: a lack of time, increased paperwork, disruption to work flows, and concern over practice finances. Similar findings have been reported in the US, UK, Europe, and Australia. However, regarding positive motivations of practices to participate, we found systematic differences in attitude between research-engaged and research-naïve practices that have not been previously reported. The research-experienced group offered a greater number and variety of reasons to take part than the not-experienced group. While both groups expressed motivations related to patient care, clinicians and staff members experienced in practice-based clinical trials were much more likely to cite intellectual, professional, and societal benefits not envisioned by the other group. CONCLUSIONS: We conclude that clinicians not already participating in practice-based trials may have a narrower range of motivations than those already participating. The lack of a broader view of possible benefits to participation may also translate into more obdurate recruiting challenges. These results point to the need for recruitment, engagement, and messaging approaches differentially tailored to the needs and interests of non-participating practices.

Fructosamine and Hemoglobin A1c Correlations in HIV-Infected Adults in Routine Clinical Care: Impact of Anemia and Albumin Levels.

Fructosamine is an alternative method to hemoglobin A1c (HbA1c) for determining average glycemia. However, its use has not been extensively evaluated in persons living with HIV (PLWH). We examined the relationship between HbA1c and fructosamine values, specifically focusing on anemia (which can affect HbA1c) and albumin as a marker of liver disease. We included 345 PLWH from two sites. We examined Spearman rank correlations between fructosamine and HbA1c and performed linear test for trends to compare fructosamine and HbA1c correlations by hemoglobin and albumin quartiles. We examined discrepant individuals with values elevated only on one test. We found a correlation of 0.70 between fructosamine and HbA1c levels. Trend tests for correlations between fructosamine and HbA1c were significant for both albumin (p = 0.05) and hemoglobin (p = 0.01) with the lowest correlations in the lowest hemoglobin quartile. We identified participants with unremarkable HbA1c values but elevated fructosamine values. These discrepant individuals had lower mean hemoglobin levels than those elevated by both tests. We demonstrated a large correlation between HbA1c and fructosamine across a range of hemoglobin and albumin levels. There were discrepant cases particularly among those with lower hemoglobin levels. Future studies are needed to clarify the use of fructosamine for diabetes management in PWLH.

An Internet-based Controlled Trial Aimed to Improve Osteoporosis Prevention among Chronic Glucocorticoid Users.

OBJECTIVE: To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using "storytelling" on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service. METHODS: We identified members who refilled ≥ 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for ≥ 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day "Video ON" periods, during which the video automatically appeared at the time of refill, and two 45-day "Video OFF" periods, during which there was no video. Members could also "self-initiate" watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months. RESULTS: Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% "self-initiated" the video. The GIOP prescription rate in the "Video ON" group was 2.9% versus 2.7% for the "Video OFF" group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1). CONCLUSION: Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689.

HIV-related metabolic comorbidities in the current ART era.

Despite effective antiretroviral therapy (ART), HIV-infected individuals have residual chronic immune activation that contributes to the pathogenesis of HIV infection. This immune system dysregulation is a pathogenic state manifested by very low naïve T-cell numbers and increased terminally differentiated effector cells that generate excessive proinflammatory cytokines with limited functionality. Immune exhaustion leaves an individual at risk for accelerated aging-related diseases, including renal dysfunction, atherosclerosis, diabetes mellitus, and osteoporosis. We highlight research that clarifies the role of HIV, ART, and other factors that contribute to the development of these diseases among HIV-infected persons.

Bone alterations associated with HIV.

HIV infection and initiation of antiretroviral therapy (ART) have been consistently associated with decreased bone mineral density (BMD), with growing evidence linking HIV to an increased risk of fracture. This is especially concerning with the expanding number of older persons living with HIV. Interestingly, recent data suggest that HIV-infected children and youth fail to achieve peak BMD, possibly increasing their lifetime risk of fracture. Elucidating the causes of the bone changes in HIV-positive persons is challenging because of the multifactorial nature of bone disease in HIV, including contribution of the virus, immunosuppression, ART toxicity, and traditional osteoporosis risk factors, such as age, lower weight, tobacco, and alcohol use. Thus, practitioners must recognize the risk of low BMD and fractures and appropriately screen patients for osteoporosis if risk factors exist. If fractures do occur or elevated fracture risk is detected through screening, treatment with bisphosphonate medications appears safe and effective in the HIV+population.

Molecular mechanism of thiazolidinedione-mediated inhibitory effects on osteoclastogenesis.

Thiazolidinediones are synthetic peroxisome proliferator-activated receptor γ agonists used to treat type 2 diabetes mellitus. Clinical evidence indicates that thiazolidinediones increase fracture risks in type 2 diabetes mellitus patients, but the mechanism by which thiazolidinediones augment fracture risks is not fully understood. Several groups recently demonstrated that thiazolidinediones stimulate osteoclast formation, thus proposing that thiazolidinediones induce bone loss in part by prompting osteoclastogenesis. However, numerous other studies showed that thiazolidinediones inhibit osteoclast formation. Moreover, the molecular mechanism by which thiazolidinediones modulate osteoclastogenesis is not fully understood. Here we independently address the role of thiazolidinediones in osteoclastogenesis in vitro and furthermore investigate the molecular mechanism underlying the in vitro effects of thiazolidinediones on osteoclastogenesis. Our in vitro data indicate that thiazolidinediones dose-dependently inhibit osteoclastogenesis from bone marrow macrophages, but the inhibitory effect is considerably reduced when bone marrow macrophages are pretreated with RANKL. In vitro mechanistic studies reveal that thiazolidinediones inhibit osteoclastogenesis not by impairing RANKL-induced activation of the NF-κB, JNK, p38 and ERK pathways in bone marrow macrophages. Nonetheless, thiazolidinediones inhibit osteoclastogenesis by suppressing RANKL-induced expression of NFATc1 and c-Fos, two key transcriptional regulators of osteoclastogenesis, in bone marrow macrophages. In addition, thiazolidinediones inhibit the RANKL-induced expression of osteoclast genes encoding matrix metalloproteinase 9, cathepsin K, tartrate-resistant acid phosphatase and carbonic anhydrase II in bone marrow macrophages. However, the ability of thiazolidinediones to inhibit the expression of NFATc1, c-Fos and the four osteoclast genes is notably weakened in RANKL-pretreated bone marrow macrophages. These in vitro studies have not only independently demonstrated that thiazolidinediones exert inhibitory effects on osteoclastogenesis but have also revealed crucial new insights into the molecular mechanism by which thiazolidinediones inhibit osteoclastogenesis.

Effect of self-referral on bone mineral density testing and osteoporosis treatment.

BACKGROUND: Despite national guidelines recommending bone mineral density screening with dual-energy x-ray absorptiometry (DXA) in women aged 65 years and older, many women do not receive initial screening. OBJECTIVE: To determine the effectiveness of health system and patient-level interventions designed to increase appropriate DXA testing and osteoporosis treatment through (1) an invitation to self-refer for DXA (self-referral); (2) self-referral plus patient educational materials; and (3) usual care (UC, physician referral). RESEARCH DESIGN: Parallel, group-randomized, controlled trials performed at Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Georgia (KPG). SUBJECTS: Women aged 65 years and older without a DXA in past 5 years. MEASURES: DXA completion rates 90 days after intervention mailing and osteoporosis medication receipt 180 days after initial intervention mailing. RESULTS: From >12,000 eligible women, those randomized to self-referral were significantly more likely to receive a DXA than UC (13.0%-24.1% self-referral vs. 4.9%-5.9% UC, P<0.05). DXA rates did not significantly increase with patient educational materials. Osteoporosis was detected in a greater proportion of self-referral women compared with UC (P<0.001). The number needed to receive an invitation to result in a DXA in KPNW and KPG regions was approximately 5 and 12, respectively. New osteoporosis prescription rates were low (0.8%-3.4%) but significantly greater among self-referral versus UC in KPNW. CONCLUSIONS: DXA rates significantly improved with a mailed invitation to schedule a scan without physician referral. Providing women the opportunity to self-refer may be an effective, low-cost strategy to increase access for recommended osteoporosis screening.

Prevention and treatment of bone changes associated with exposure to glucocorticoids.

Rheumatologic diseases are associated with a proinflammatory state, which is thought to lead to many of the bone changes seen in treatment-naive patients. However, glucocorticoids remain a common treatment option for rheumatologic diseases and are known to have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Despite the anti-inflammatory effect of glucocorticoids, fracture risk rises within the first 3 months of treatment. As such, osteoporosis prevention and treatment needs to be considered in all patients started on chronic glucocorticoids (≥3 months of treatment). For very low risk patients, conservative management with non-pharmacologic strategies may be appropriate. For the moderate to high fracture risk patients treated with glucocorticoids, pharmacologic treatment with 1 of the 4 approved medications should be considered. The challenge of educating physicians and patients of the risks of glucocorticoid induced osteoporosis remain.

Using tablet computers compared to interactive voice response to improve subject recruitment in osteoporosis pragmatic clinical trials: feasibility, satisfaction, and sample size.

INTRODUCTION: Pragmatic clinical trials (PCTs) provide large sample sizes and enhanced generalizability to assess therapeutic effectiveness, but efficient patient enrollment procedures are a challenge, especially for community physicians. Advances in technology may improve methods of patient recruitment and screening in PCTs. Our study looked at a tablet computer versus an integrated voice response system (IVRS) for patient recruitment and screening for an osteoporosis PCT in community physician offices. MATERIALS AND METHODS: We recruited women ≥ 65 years of age from community physician offices to answer screening questions for a hypothetical osteoporosis active comparator PCT using a tablet computer or IVRS. We assessed the feasibility of these technologies for patient recruitment as well as for patient, physician, and office staff satisfaction with the process. We also evaluated the implications of these novel recruitment processes in determining the number of primary care practices and screened patients needed to conduct the proposed trial. RESULTS: A total of 160 women (80% of those approached) agreed to complete the osteoporosis screening questions in ten family physicians' offices. Women using the tablet computer were able to complete all screening questions consistently and showed a nonsignificant trend towards greater ease of use and willingness to spend more time in their physician's office compared to those using IVRS. Using the proportion of women found to be eligible in this study (almost 20%) and other eligibility scenarios, we determined that between 240 and 670 community physician offices would be needed to recruit ample patients for our hypothetical study. CONCLUSION: We found good satisfaction and feasibility with a tablet computer interface for the recruitment and screening of patients for a hypothetical osteoporosis PCT in community office settings. In addition, we used this experience to estimate the number of research sites needed for such a study.

Study design considerations for a large simple trial of bisphosphonates.

PURPOSE OF REVIEW: To evaluate design considerations for an osteoporosis large simple trial (LST). RECENT FINDINGS: There is a growing need for more comparative effectiveness studies in osteoporosis. However, the design of such studies is challenged by issues surrounding study design, choosing comparator therapies, participant and outcome selection, data acquisition and data analysis. SUMMARY: LSTs are real-world studies that can have high levels of generalizability, if designed properly. We propose novel approaches to LSTs focusing on some of the challenges associated with comparative effectiveness research in osteoporosis. In this review, we discuss these considerations in the context of bisphosphonate active comparator initiation and discontinuation trials, while presenting advantages and disadvantages of the various design aspects for such studies.

Osteoporosis diagnosis and medical treatment.

Osteoporosis, the presence of either low bone mineral density or a history of a fragility fracture, is known to be associated with an increased risk of future fracture. Fracture prevention is possible through use of both nonpharmacologic and prescription treatments. Despite recent controversy regarding the safety of calcium supplementation and the appropriate dosing of calcium and vitamin D, calcium and vitamin D remain an important part of bone health. However, prescription osteoporosis treatments should be considered for those at higher risk for fracture, and there are currently several treatment options available.

Low hemoglobin levels and recurrent falls in U.S. men and women: prospective findings from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: There are few data available on low hemoglobin and incident falls in the general U.S. population. METHODS: Of 30,239 black and white U.S. adults ≥45 years in the population-based REasons for Geographic And Racial Differences in Stroke study, 16,782 had hemoglobin measured at baseline and follow-up data on falls. Hemoglobin was categorized by 1.0 g/dL increments relative to the World Health Organization anemia threshold (<13.0 g/dL for men, <12.0 g/dL for women). Recurrent falls (≥2 falls in the 6 months after baseline) were assessed during a telephone interview. RESULTS: Recurrent falls occurred in 3.9% of men and 4.8% of women. Compared with those with a hemoglobin level 1 to 2 g/dL above the anemia cut-off, multivariable adjusted odds ratios (95% confidence intervals) for recurrent falls associated with hemoglobin levels ≥3, 2 to <3 and 0 to 1 g/dL above the cut-off point, and 0 to <1 and ≥1 g/dL below the cut-off point were 0.73 (0.45-1.19), 0.84 (0.57-1.24), 1.29 (0.88-1.90), 1.32 (0.0.80-1.2.18) and 2.12 (1.23-3.63), respectively, among men (linear trend P < 0.001), and 1.59 (1.10-2.3), 1.24 (0.95-1.62), 1.42(1.11-1.81), 1.28 (0.91-1.80) and 1.76 (1.13-2.74), respectively, among women (linear trend P = 0.45; quadratic trend P = 0.016). CONCLUSIONS: Among men, lower hemoglobin levels were associated with an increased risk for recurrent falls. Although our findings suggest an increased risk for recurrent falls at both lower and higher hemoglobin levels among women, these findings should be confirmed in subsequent studies.

Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids.

PURPOSE OF REVIEW: Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. RECENT FINDINGS: Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. SUMMARY: Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.