The American Society for Bone and Mineral Research Task Force on clinical algorithms for fracture risk report.

Using race and ethnicity in clinical algorithms potentially contributes to health inequities. The American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee convened the ASBMR Task Force on Clinical Algorithms for Fracture Risk to determine the impact of race and ethnicity adjustment in the US Fracture Risk Assessment Tool (US-FRAX). The Task Force engaged the University of Minnesota Evidence-based Practice Core to conduct a systematic review investigating the performance of US-FRAX for predicting incident fractures over 10 years in Asian, Black, Hispanic, and White individuals. Six studies from the Women's Health Initiative (WHI) and Study of Osteoporotic Fractures (SOF) were eligible; cohorts only included women and were predominantly White (WHI > 80% and SOF > 99%), data were not consistently stratified by race and ethnicity, and when stratified there were far fewer fractures in Black and Hispanic women vs White women rendering area under the curve (AUC) estimates less stable. In the younger WHI cohort (n = 64 739), US-FRAX without bone mineral density (BMD) had limited discrimination for major osteoporotic fracture (MOF) (AUC 0.53 (Black), 0.57 (Hispanic), and 0.57 (White)); somewhat better discrimination for hip fracture in White women only (AUC 0.54 (Black), 0.53 (Hispanic), and 0.66 (White)). In a subset of the older WHI cohort (n = 23 918), US-FRAX without BMD overestimated MOF. The Task Force concluded that there is little justification for estimating fracture risk while incorporating race and ethnicity adjustments and recommends that fracture prediction models not include race or ethnicity adjustment but instead be population-based and reflective of US demographics, and inclusive of key clinical, behavioral, and social determinants (where applicable). Research cohorts should be representative vis-à-vis race, ethnicity, gender, and age. There should be standardized collection of race and ethnicity; collection of social determinants of health to investigate impact on fracture risk; and measurement of fracture rates and BMD in cohorts inclusive of those historically underrepresented in osteoporosis research.

Using race or ethnicity when calculating disease risk may contribute to health disparities. The ASBMR Task Force on Clinical Algorithms for Fracture Risk was created to understand the impact of the US Fracture Risk Assessment Tool (US-FRAX) race and ethnicity adjustments. The Task Force reviewed the historical development of FRAX, including the assumptions underlying selection of race and ethnicity adjustment factors. Furthermore, a systematic review of literature was conducted, which revealed an overall paucity of data evaluating the performance of US-FRAX in racially and ethnically diverse groups. While acknowledging the existence of racial and ethnic differences in fracture epidemiology, the Task Force determined that currently there is limited evidence to support the use of race and ethnicity­specific adjustments in US-FRAX. The Task Force also concluded that research is needed to create generalizable fracture risk calculators broadly applicable to current US demographics, which do not include race and ethnicity adjustments. Until such population­based fracture calculators are available, clinicians should consider providing fracture risk ranges for Asian, Black, and/or Hispanic patients and should engage in shared decision-making with patients about fracture risk interpretation. Future studies are required to evaluate fracture risk tools in populations inclusive of those historically underrepresented in research.

Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene.

Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children ("primary" stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

Clinical features of COVID-19 rapid antigen test exposures reported by an Australian poisons information centre: a prospective study.

INTRODUCTION: Coronavirus disease COVID-19 rapid antigen tests are a useful tool in detecting infection, and their use has increased in many countries since they became commercially available in late 2021. Some rapid antigen tests contain sodium azide, which can be toxic in small doses. This study aimed to describe the clinical characteristics of exposures to COVID-19 rapid antigen tests. METHODS: This is a prospective study conducted by the New South Wales Poisons Information Centre. From 22 January 2022 to 31 August 2022, rapid antigen test exposures were followed up to obtain outcome information. Data collected included: brand/ingredients, exposure route, demographics, symptoms, and disposition. RESULTS: We recorded 218 exposures in the seven-month study period. Complete follow-up information was available in 75% (n = 164). There were 53 exposures to sodium azide-containing products (35 with follow-up data) and 165 to non-sodium azide-containing products and unknown ingredient exposures (129 with follow-up data). Overall, unintentional exposures predominated (n = 182), and 151 were ingestions. The vast majority (>90%) did not develop symptoms, and all symptoms that developed were mild. Most cases (95%, n = 208) did not require referral to a healthcare facility. CONCLUSIONS: In this prospective series, few patients developed symptoms, regardless of the sodium azide content, likely due to low concentration and low volume within the test kits. However, ongoing toxicovigilance is warranted.

Beyond the Surgical Safety Checklist: Using Intraoperative Handoff to Facilitate Team Situation Awareness in the OR.

BACKGROUND: The surgical safety checklist (SSC) has been credited with improving team situation awareness (SA) in the operating room. Although the SSC may support team SA at the outset of the operative case, intraoperative handoff provides an opportunity for either SA breakdown or, more preferably, SA reinforcement. High-functioning surgical teams demonstrate a high level of continued SA, whereas teams deficient in SA are more likely to be affected by surgical errors and adverse events. To date, no interprofessional intraoperative tools exist to support team SA beyond the SSC. METHODS: This study was divided into 2 phases. The first used qualitative methods to (1) characterize intraoperative handoff processes across surgery, nursing, anesthesia, and perfusion, and (2) identify cultural factors that shaped handoff practices. Data for phase one were collected over 38 observation days and 41 brief interviews. Phase 2, informed by phase 1, used a modified Delphi process to create a tool for use during intraoperative handoff. Data were analyzed iteratively. RESULTS: Handoff practices were not standardized and rarely involved the entire team. In addition we uncovered cultural factors-specifically assumptions held by participants-that hindered team communication during handoff. Assumptions included: (1) team members are interchangeable, (2) trained individuals are able to determine when it is appropriate to handoff without consulting the OR team. Despite claims of improved teamwork resulting from the SSC, many participants held a fragmented view of the OR team, resulting in communication challenges during handoff. Findings from both phases of our study informed the development of multidisciplinary intraoperative handoff tools to facilitate shared team situation awareness and a shared mental model. CONCLUSIONS: Intraoperative handoff occurs frequently, and offers the opportunity for either renewed or fractured team SA beyond the SSC.

The Consumption of Animal and Plant Foods in Areas of High Prevalence of Stroke and Colorectal Cancer.

Diets of red and processed meat have been reported as important risk factors for developing colorectal cancer. Given the racial and ethnic differences in the incidence of colorectal cancer, patterns of food consumption, and areas of residence, particularly in the South, more data is needed on the relationship between residing in a high stroke area, colorectal cancer incidence levels, and red meat and processed meat consumption. We created online surveys to ascertain meat, red meat, and healthy food consumption levels. We used OLS regression to evaluate the association between residence in Stroke Belt states and colorectal cancer incidence quartiles with food consumption. We further used path analysis using structural equation modeling to evaluate if age, sex, race/ethnicity, income, and comorbidity index mediated the association between residence in the eight-state Stroke Belt, colorectal cancer incidence groups, and meat consumption. Our sample included 923 participants, with 167 (18.1%) residing in the Stroke Belt and 13.9% being in the highest colorectal cancer incidence group. The findings show that residing in a Stroke Belt state is predictive of the consumption of overall meat 0.93 more days per week or red meat 0.55 more days per week compared to those not residing in a Stroke Belt state. These data can be used to develop future diet interventions in these high-risk areas to reduce rates of colorectal cancer and other negative health outcomes.

Gi/o protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation.

Gi/o-coupled somatostatin or α2-adrenergic receptor activation stimulated ß-cell NKA activity, resulting in islet Ca2+ fluctuations. Furthermore, intra-islet paracrine activation of ß-cell Gi/o-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca2+ oscillations, which decreased insulin secretion. ß-cell membrane potential hyperpolarization resulting from Gi/o-GPCR activation was dependent on NKA phosphorylation by Src tyrosine kinases. Whereas, ß-cell NKA function was inhibited by cAMP-dependent PKA activity. These data reveal that NKA-mediated ß-cell membrane potential hyperpolarization is the primary and conserved mechanism for Gi/o-GPCR control of electrical excitability, Ca2+ handling, and insulin secretion.

Recent Stressful Life Events, Lifetime Traumatic Events, Missed Visits, and Antiretroviral Adherence Among Black Women With HIV in the Southeastern United States: A Cross-sectional Study.

ABSTRACT: Lifetime traumatic events are prevalent among people with HIV and consistently associated with deleterious HIV outcomes. Yet, little is known about the impact of recent stressful events on health outcomes among Black women with HIV (WWH). This cross-sectional study assessed the prevalence of recent stressful events and lifetime traumatic events and their association with HIV outcomes in Black WWH ( n = 200) in the Southeastern United States. We evaluated the association between stressful events and HIV outcomes using chi-square tests and unadjusted and adjusted logistic regression analyses. In the unadjusted analyses, missed visits were associated with higher odds of recent stressful events (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.04-1.16) and lifetime traumatic events (OR 1.15, 95% CI 1.05-1.26). In the adjusted analysis, exposure to recent stressful events was independently associated with missed visits (adjusted OR 1.08, 95% CI 1.01-1.15). Interventions addressing recent stressful events are warranted.

The Relationship Between Prior Cancer Diagnosis and All-Cause Dementia Progression Among US Adults.

BACKGROUND: Cancer-related cognitive impairment (CRCI), a frequent effect of cancer and its treatments, shares common cognitive symptoms with dementia syndromes. Cross-sectional studies demonstrate an inverse relationship between cancer and dementia. However, the longitudinal relationship between dementia decline and cancer has not been investigated. OBJECTIVE: To evaluate the association between cancer and longitudinal progression of dementia. METHODS: We extracted electronic health record data from July 2003 to February 2020 from a single academic medical center. We identified dementia and cancer history prior to dementia using ICD-9/10 codes. We measured cognitive decline with the Alabama Brief Cognitive Screener (ABCs). We used adjusted linear mixed models to estimate baseline cognition and rate of progression by cancer history, including differences by race. RESULTS: The study included 3,809 participants with dementia, of which 672 (17.6%) had cancer history. Those with cancer history had higher baseline cognition (ß: 1.07, 95% CI: 0.45, 1.69), but similar rate of decline. Non-Hispanic Blacks had lower cognitive scores at baseline and throughout follow-up regardless of cancer status compared to non-Hispanic Whites and other races/ethnicities with and without cancer history. CONCLUSION: In this longitudinal retrospective study, participants with cancer history demonstrate better cognition at dementia diagnosis and no difference in cognitive decline than those without cancer history. Smoking and comorbidities attenuate this association and results indicate non-Hispanic Blacks have worse cognitive outcomes in dementia regardless of cancer history than other race/ethnicity groups. Further exploration of the role of smoking, comorbidities, and race/ethnicity on cancer and dementia-related cognitive decline is needed.

Synthesis of the Aeromonas veronii strain Bs8 disaccharide repeating unit.

Presented herein is the synthesis of the Aeromonas veronii disaccharide repeating unit which has been achieved in 11 steps starting from d-fucose and d-galactosamine.

Efficacy of Early Preventive Dental Services in Primary Medical Care Setting: Results From Alabama's 1st Look Program.

Purpose: To evaluate early preventive dental services (PDS) provided by primary care providers (PCPs) in reducing future caries treatments among Alabama Medicaid recipients. Methods: Data from 2009 to 2019 Alabama Medicaid were used to evaluate effectiveness of 1st Look Program on PDS before age three years and incidence of caries treatments after age three years. PDS groups consisted of 1st Look-involved (PDS claims from PCPs), dentist-only (PDS claims from dental providers), and no early fluoride treatment participants (no PDS claims before age three years). Outcomes included frequency and expenditures of fluoride applications, simple restorations, and extensive treatments. Regression models were used to evaluate associations between PDS groups and outcomes while controlling for covariates. Results: Children in 1st Look- involved received more fluoride (3.0 versus 2.1 times; P<0.001) and were applied earlier (12.1 versus 22.9 months old; P<0.001) than dentist-only group. After adjusting for covariates, compared to dentist-only, 1st Look-involved group received earlier fluoride (beta value equals -11.1 months; 95 percent confidence interval [95% CI] equals -11.25 to -10.97) with greater frequency (incident rate ratio equals 1.49; 95% CI equals 1.47 to 1.51). Caries treatment counts were highest in dentist-only followed by 1st Look-involved and no early fluoride treatment groups in both simple restorations (2.7 versus 2.0 versus 0.2 times; P<0.001) and extensive treatments (2.8 versus 2.3 versus 0.2 times; P<0.001), which were consistent after adjusting for covariates. Conclusions: PDS were provided earlier by PCPs in Medicaid-qualified children, with reduced caries treatments on primary teeth, compared to PDS by dental providers only.

Racial and Ethnic Disparities in Bone Health and Outcomes in the United States.

Osteoporosis is a bone disease classified by deterioration of bone microarchitecture and decreased bone strength, thereby increasing subsequent risk of fracture. In the United States, approximately 54 million adults aged 50 years and older have osteoporosis or are at risk due to low bone mass. Osteoporosis has long been viewed as a chronic health condition affecting primarily non-Hispanic white (NHW) women; however, emerging evidence indicates racial and ethnic disparities in bone outcomes and osteoporosis management. The primary objective of this review is to describe disparities in bone mineral density (BMD), prevalence of osteoporosis and fracture, as well as in screening and treatment of osteoporosis among non-Hispanic black (NHB), Hispanic, and Asian adults compared with NHW adults living on the US mainland. The following areas were reviewed: BMD, osteoporosis prevalence, fracture prevalence and incidence, postfracture outcomes, DXA screening, and osteoporosis treatments. Although there are limited studies on bone and fracture outcomes within Asian and Hispanic populations, findings suggest that there are differences in bone outcomes across NHW, NHB, Asian, and Hispanic populations. Further, NHB, Asian, and Hispanic populations may experience suboptimal osteoporosis management and postfracture care, although additional population-based studies are needed. There is also evidence that variation in BMD and osteoporosis exists within major racial and ethnic groups, highlighting the need for research in individual groups by origin or background. Although there is a clear need to prioritize future quantitative and qualitative research in these populations, initial strategies for addressing bone health disparities are discussed. © 2021 American Society for Bone and Mineral Research (ASBMR).

The Contribution of Patient, Primary Care Physician, and Primary Care Clinic Factors to Good Bone Health Care.

BACKGROUND/OBJECTIVE: Patient, provider, and system factors can contribute to chronic care management and outcomes. Few studies have examined these multilevel associations with osteoporosis care and outcomes. We examined how key process and structural factors at the patient, primary care physician (PCP), and primary care clinic (PCC) levels were associated with guideline concordant osteoporosis pharmacotherapy, daily calcium intake, vitamin D supplementation, and weekly exercise sessions at 52 weeks following enrollment in a cluster randomized controlled trial. METHODS: We conducted a secondary analysis of observational data from 1 site of the trial. The study sample included 1996 men and women ≥ 50 years of age at the time of recruitment following completion of a dual-energy x-ray absorptiometry (DXA) scan and who had complete data at baseline and 52 weeks. Our primary independent variable was "relationship continuity": the DXA-ordering provider was the patient's PCP. Hierarchical linear and logistic regression accounted for patient, provider, and primary care clinic characteristics. RESULTS: In multivariable regression analyses, relationship continuity (ie, the PCP ordered the study DXA) was associated with higher average daily calcium intake and likelihood of vitamin D supplementation at 52 weeks. No PCP or primary care clinic factors were associated with osteoporosis care. CONCLUSIONS: The relationship continuity, in which the provider ordering a DXA is the patient's PCP and therefore also presents the results of a DXA, may help to promote patient behaviors associated with good bone health.

Chlamydia Prevalence by Age and Correlates of Infection Among Pregnant Women.

BACKGROUND: There is a paucity of population-based data on chlamydia in pregnancy despite rising rates in US women. Our objectives were to assess chlamydia prevalence by age group and to identify factors associated with infection in pregnant women to inform screening guidelines. METHODS: This cross-sectional study included pregnant women tested for chlamydia who delivered at the University of Alabama at Birmingham between November 1, 2012, and December 31, 2017. The primary outcome was chlamydia prevalence, defined as a positive urogenital chlamydia nucleic acid amplification test result documented in the electronic medical record. Multivariable logistic regression was used to identify factors associated with infection. RESULTS: Among 17,796 women who delivered during the study period, 13,657 (77%) had chlamydia testing performed at the University of Alabama at Birmingham. Chlamydia prevalence (95% confidence interval) was 7.4% (7.0%-7.9%). Age-stratified prevalence rates were 14.6%, 4.3%, and 1.7% for women younger than 25 years, 25 to 29 years, and 30 years or older, respectively. Chlamydia in pregnancy remained strongly associated with age (adjusted odds ratio [95% confidence interval], 7.2 [5.6-9.2] for age <25 years, and 2.3 [1.7-3.0] for ages 25-29 years, when compared with >30 years) after adjustment for race, urban residence, and insurance status. CONCLUSIONS: Among pregnant women living in the southeastern United States, chlamydia was detected in 1 of 14 women who were tested. Chlamydia positivity was highest among women younger than 30 years. Study findings support broad screening for chlamydia in pregnancy.

Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women.

Importance: Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture. Objective: To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone. Design, Setting, and Participants: The Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019. Main Outcomes and Measures: Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up. Results: Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score. Conclusions and Relevance: The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.

Secular Trends in the Incidence of Hip Fracture Among Nursing Home Residents.

A recent study suggested a decline in the incidence of hip fracture among US women between 2002 and 2012, followed by a leveling in the incidence rate from 2013 to 2015. Newly admitted nursing home residents are particularly vulnerable to hip fracture, and it is unclear whether that trend is observed in this high risk group. The purpose of our study was to describe trends in hip fracture rates and postfracture mortality among 2.6 million newly admitted US nursing home residents from 2007 to 2015, and to examine whether these trends could be explained by differences in resident characteristics. Medicare claims data were linked with the Minimum Data Set (MDS), a clinical assessment performed quarterly on all nursing home residents. In each year (2007-2015), we identified newly admitted long-stay (ie, 100 days in the same facility) nursing home residents. Hip fracture was defined using Medicare Part A diagnostic codes. Follow-up time was calculated from the index date until the first event of hospitalized hip fracture, Medicare disenrollment, death, or until 1 year. Poisson regression was used to adjust rates of hip fracture for age and sex. The number of newly admitted nursing home residents ranged from 324,508 in 2007 to 257,350 in 2015. Although mean age remained similar (83 years), residents were more functionally dependent over time. There was a small absolute decrease in the incidence rate of hip fracture between 2007 (3.32/100 person-years) and 2013 (2.82/100 person-years), with an increase again in 2015 (3.03/100 person-years). Adjusting for patient characteristics somewhat attenuated these trends. One-year mortality was high following fracture in all years (42.6% in 2007, 42.1% in 2014). In summary, we observed a recent slight rise in the incidence rates of hip fracture among nursing home residents that was at least partially explained by differences in resident characteristics over time. © 2020 American Society for Bone and Mineral Research.

Racial Disparities Exist in Outcomes After Major Fragility Fractures.

BACKGROUND: Fractures associated with postmenopausal osteoporosis (PMO) are associated with pain, disability, and increased mortality. A recent, nationwide evaluation of racial difference in outcomes after fracture has not been performed. OBJECTIVE: To determine if 1-year death, debility, and destitution rates differ by race. DESIGN: Observational cohort study. SETTING: US Medicare data from 2010 to 2016. PARTICIPANTS: Non-Hispanic black and white women with PMO who have sustained a fragility fracture of interest: hip, pelvis, femur, radius, ulna, humerus, and clinical vertebral. MEASUREMENTS: Outcomes included 1-year: (1) mortality, identified by date of death in Medicare vital status information, (2) debility, identified as new placement in long-term nursing facilities, and (3) destitution, identified as becoming newly eligible for Medicaid. RESULTS: Among black and white women with PMO (n = 4,523,112), we identified 399,000 (8.8%) women who sustained a major fragility fracture. Black women had a higher prevalence of femur (9.0% vs 3.9%; P < .001) and hip (30.7% vs 28.0%; P < .001) fractures and lower prevalence of radius/ulna (14.7% vs 17.0%; P < .001) and clinical vertebral fractures (28.8% vs 33.5%; P < .001) compared with white women. We observed racial differences in the incidence of 1-year outcomes after fracture. After adjusting for age, black women had significantly higher risk of mortality 1 year after femur, hip, humerus, and radius/ulna fractures; significantly higher risk of debility 1 year after femur and hip fractures; and significantly higher risk of destitution for all fractures types. CONCLUSIONS: In a sample of Medicare data from 2010 to 2016, black women with PMO had significantly higher rates of mortality, debility, and destitution after fracture than white women. These findings are a first step toward understanding and reducing disparities in PMO management, fracture prevention, and clinical outcomes after fracture. J Am Geriatr Soc 68:1803-1810, 2020.

Osteoporosis screening using computed tomography for men with prostate cancer: results of a prospective study.

We performed a prospective study using both FRAX and computed tomography to screen for osteoporosis in men undergoing radiation for prostate cancer. We found that implementing routine computed tomography (CT)-based screening was feasible in the setting of a prospective study, but the yield of osteoporosis identification was low in this population. PURPOSE: Men with prostate cancer (PCa) are at increased risk of hip fracture for multiple reasons. Estimation of hip fracture risk with the FRAX tool is currently recommended, but FRAX alone may not identify a portion of men with osteoporosis. We hypothesized that adding bone mineral density (BMD) screening using CT to FRAX is feasible and would identify more men with osteoporosis. METHODS: Men with PCa scheduled to undergo CT simulation for radiation treatment were enrolled in a single-arm prospective study. The mean attenuation of the mid-L5 vertebral body trabecular bone (L5CT) was calculated on a single slice using the radiation simulation CT scan. The 10-year risk of hip fracture was calculated using the FRAX tool. Dual energy X-ray absorptiometry (DXA) was performed for men whose L5CT measurement was less than 130 Hounsfield units (HU). RESULTS: A total of 98 eligible men were enrolled and underwent FRAX and CT screening. The median 10-year risk of hip fracture was 1.1% and exceeded 3% in 16 cases; the median L5CT was 162.28 HU (range 55.6-526.1 HU). DXA scan was completed in 15 men who had L5CT < 130 HU but 10-year calculated hip fracture risk < 3%, 1 of whom was found to have osteoporosis (T-score ≤ -2.5). CONCLUSIONS: Implementing CT-based BMD screening was feasible in the setting of a prospective study for men receiving radiation for PCa, but fewer cases than anticipated of osteoporosis were identified.

Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk.

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.

Temporal Trends and Factors Associated with Bisphosphonate Discontinuation and Restart.

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as ≥12 months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12 months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. © 2019 American Society for Bone and Mineral Research.