Genetic variants and physical activity interact to affect bone density in Hispanic children.

BACKGROUND: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study. METHODS: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD. RESULTS: We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (ß = - 0.040 ± 0.009, p = 1.1 × 10- 5) and lumbar spine BMD (ß = - 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (ß = - 0.015 ± 0.006, p = 0.02; ß = 0.008 ± 0.01, p = 0.4, respectively). DISCUSSION: The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed. CONCLUSIONS: Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.

Screening for Osteoporosis in Older Men: Operating Characteristics of Proposed Strategies for Selecting Men for BMD Testing.

BACKGROUND: The optimal approach for selecting men for bone mineral density (BMD) testing to screen for osteoporosis is uncertain. OBJECTIVE: To compare strategies for selecting older men for screening BMD testing. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 4043 community-dwelling men aged ≥70 years at four US sites. MAIN MEASURES: BMD at the total hip, femoral neck, and lumbar spine using dual-energy x-ray absorptiometry (DXA). Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating curve (AUC) of the Osteoporosis Self-Assessment Tool (OST) and Fracture Risk Assessment Tool (FRAX) without BMD to discriminate between those with and without osteoporosis as defined by World Health Organization (WHO) diagnostic criteria, and between those recommended and not recommended for pharmacologic therapy based on the National Osteoporosis Foundation (NOF) guidelines. KEY RESULTS: Among the cohort, 216 (5.3%) had a BMD T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine, and 1184 (29.2%) met criteria for consideration of pharmacologic therapy according to NOF guidelines. The OST had better discrimination (AUC 0.68) than the FRAX (AUC 0.62; p = 0.004) for identifying T-score-defined osteoporosis. Use of an OST threshold of <2 resulted in sensitivity of 0.83 and specificity of 0.36 for the identification of osteoporosis, compared to sensitivity of 0.59 and specificity of 0.59 for the use of FRAX with a cutoff of 9.3% 10-year risk of major osteoporotic fracture. CONCLUSIONS: The OST performs modestly better than the more complex FRAX in selecting older men for BMD testing to screen for osteoporosis; the use of either tool substantially reduces the proportion of men referred for BMD testing compared to universal screening. Of 1000 men aged 70 and older in this community-based cohort, the use of an OST cutoff of <2 to select men for BMD testing would result in 654 men referred for BMD testing, of whom 44 would be identified as having osteoporosis, and nine with osteoporosis would be missed.

Bone-density testing interval and transition to osteoporosis in older women.

BACKGROUND: Although bone mineral density (BMD) testing to screen for osteoporosis (BMD T score, -2.50 or lower) is recommended for women 65 years of age or older, there are few data to guide decisions about the interval between BMD tests. METHODS: We studied 4957 women, 67 years of age or older, with normal BMD (T score at the femoral neck and total hip, -1.00 or higher) or osteopenia (T score, -1.01 to -2.49) and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis, followed prospectively for up to 15 years. The BMD testing interval was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustment for estrogen use and clinical risk factors. Transitions from normal BMD and from three subgroups of osteopenia (mild, moderate, and advanced) were analyzed with the use of parametric cumulative incidence models. Incident hip and clinical vertebral fractures and initiation of treatment with bisphosphonates, calcitonin, or raloxifene were treated as competing risks. RESULTS: The estimated BMD testing interval was 16.8 years (95% confidence interval [CI], 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI, 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia. CONCLUSIONS: Our data indicate that osteoporosis would develop in less than 10% of older, postmenopausal women during rescreening intervals of approximately 15 years for women with normal bone density or mild osteopenia, 5 years for women with moderate osteopenia, and 1 year for women with advanced osteopenia. (Funded by the National Institutes of Health.).

Bone Density Screening and Re-screening in Postmenopausal Women and Older Men.

Clinical practice guidelines universally recommend bone mineral density (BMD) screening to identify osteoporosis in women aged 65 years and older. Risk assessment is recommended to guide BMD screening in postmenopausal women under age 65. Insufficient data are available to inform standard ages to start and stop BMD screening in postmenopausal women. Based on longitudinal studies of incident osteoporosis and fracture in postmenopausal women, an initial BMD test should be ordered for all women aged 65, and the frequency of re-screening should be based on age and BMD T score (more frequent testing for older age and lower T score). Although clinical practice guidelines recommend BMD screening according to risk factors for fracture in postmenopausal women under age 65, no standard approach to risk assessment exists. Minimal evidence is available to guide osteoporosis screening in men, but some experts recommend initiation of BMD screening in men at age 70.

DXA Utilization Between 2006 and 2012 in Commercially Insured Younger Postmenopausal Women.

Reimbursement for dual-energy X-ray absorptiometry (DXA) scans in the outpatient setting has declined significantly since 2006. Research through 2011 has suggested reimbursement reductions for DXA scans have corresponded with an overall decreased utilization of DXA. This study updates utilization estimates for DXAs through 2012 in patients with commercial insurance and compares DXA rates before and after reimbursement changes. We evaluated DXA utilization for women aged 50-64 yr from Marketscan Commercial Claims and Encounter database between January 2006 and December 2012 based on CPT codes. We estimated utilization rates per 1000 person years (PY). We also used segmented regression analysis of monthly rates to evaluate the change in utilization rates after a proposed reimbursement reduction in July 2009. In women aged 50-64 yr, 451,656 DXAs were performed in 2006, a rate of 144 DXAs per 1000 PY. This rate increased to 149 DXAs per 1000 PY in 2009 before decreasing to 110 DXAs per 1000 PY or 667,982 scans in 2012. DXA utilization increased by 2.24 per 1000 PY until July 2009 then declined by 12.98 DXAs per 1000 persons, resulting in 37.5 DXAs per PY fewer performed in 2012 compared with 2006. Since July 2009 a significant decline in DXA utilization occurred in a younger postmenopausal commercially insured population. This decline corresponds with a time period of reductions in Medicare DXA reimbursement.

Salmon calcitonin use and associated cancer risk.

OBJECTIVE: To evaluate the strength of evidence supporting a possible association between salmon calcitonin (SCT) use and cancer incidence. DATA SOURCES: Searches of MEDLINE/PubMed, MEDLINE/OVID, and EMBASE (January 1973 to September 2013) were performed using the key search terms salmon calcitonin, humans, nasal calcitonin, and (for EMBASE only) randomized controlled trial. We also performed a manual review of data reviewed by the US Food and Drug Administration (FDA) committee in 2013. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. DATA SYNTHESIS: Intranasal and injectable SCT are FDA-approved for the treatment of postmenopausal osteoporosis. After a safety signal suggested a possible link between SCT use and prostate cancer, the European Medicines Agency and FDA regulatory agencies conducted analyses of SCT randomized controlled trial data to assess cancer-related adverse events and to readdress the approval status of SCT. Eighteen studies were found that compared nasal or oral SCT and placebo. In 15 of the 18 studies, the percentage of malignancy was greater in the SCT arm. The studies varied in quality, outcomes, and length. Most of the studies had poor-quality methods to assess new cancer cases. CONCLUSIONS: Current evidence may suggest an association between SCT use and cancer incidence based on studies with poor-quality cancer assessment methods. However, considering the lack of demonstrated efficacy of SCT to reduce fractures, clinicians should consider discontinuing its use for osteoporosis treatment regardless of the FDA's final approval decision.

Correction to: Comparison of 8-year knee osteoarthritis progression in 2 siblings: a case-based review.

The original version of this article was revised due to a retrospective Open Access order.

Comparison of 8-year knee osteoarthritis progression in 2 siblings: a case-based review.

Because the pathophysiology of knee osteoarthritis is poorly understood, optimal evidence-based clinical management is uncertain. Sibling comparison studies can help inform a clinical model to guide preventive care. We compared the 8-year clinical outcomes in 2 sisters with a family history of osteoarthritis, normal BMI, and absence of knee pain at baseline. Both patients had Kellgren-Lawrence grade 1 in the affected knee at the time of twisting knee injuries leading to osteoarthritis diagnoses at age 50 (patient 1) and 51 (patient 2). Patient 1 developed a chronic right knee effusion, and progressed to Kellgren-Lawrence grade 3 bilaterally by the time she had a right total knee replacement at age 58. Patient 2 had subchondral fractures of the right knee with transient effusion, which healed after 1 year of partial weight-bearing with crutches and subsequent daily use of knee sleeves. Patient 2 had Kellgren-Lawrence grade 0 bilaterally upon surveillance imaging at age 58. The terms "osteoarthritis and knee and diagnostic imaging and subchondral bone and pathophysiology" were searched in the PubMed database to identify original research articles to inform a clinical model consistent with the patients' outcomes. A fluid model of osteoarthritis was the best explanatory model for the discordant clinical trajectories of the age-matched siblings. Patient recommendations are presented based on these findings.

Safety and efficacy of lumen-apposing metal stents versus plastic stents to treat walled-off pancreatic necrosis: systematic review and meta-analysis.

Background and study aims Lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off pancreatic necrosis (WON). Recent studies suggested greater adverse event (AE) rates with LAMS for WON. We conducted a systematic review and meta-analysis to compare the safety and efficacy of LAMS with double-pigtail plastic stents (DPPS) for endoscopic drainage of WON. The primary aim was to evaluate stent-related AEs. Methods In October 2019, we searched the Ovid (Embase, MEDLINE, Cochrane) and Scopus databases for studies assessing a specific LAMS or DPPS for WON drainage conducted under EUS guidance. Safety outcomes were AE rates of bleeding, stent migration, perforation, and stent occlusion. Efficacy outcomes were WON resolution and number of procedures needed to achieve resolution. A subanalysis including non-EUS-guided cases was performed. Results Thirty studies including one randomized controlled trial (total 1,524 patients) were analyzed. LAMS were associated with similar bleeding (2.5 % vs. 4.6 %, P =  0.39) and perforation risk (0.5 % vs. 1.1 %, P =  0.35) compared to DPPS. WON resolution (87.4 % vs. 87.5 %, P =  0.99), number of procedures to achieve resolution (2.09 vs. 1.88, P =  0.72), stent migration (5.9 % vs. 6.8 %, P =  0.79), and stent occlusion (3.8 % vs. 5.2 %, P =  0.78) were similar for both groups. Inclusion of non-EUS-guided cases led to significantly higher DPPS bleeding and perforation rates. Conclusions LAMS and DPPS were associated with similar rates of AEs and WON resolution when limiting analysis to EUS-guided cases. Higher bleeding rates were seen in historical studies of DPPS without EUS guidance. Additional high-quality studies of WON treatment using consistent outcome definitions are needed.

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children.

CONTEXT: Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied. OBJECTIVE: We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children. METHODS: We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1030 Hispanic children (4-19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry. RESULTS: Significant heritability were observed for BMC and BMD at multiple skeletal sites ranging between 44 and 68% (P < 2.8 × 10-9). Significant evidence for linkage was found for BMD of pelvis and left leg on chromosome 7p14, lumbar spine on 20q13 and left rib on 6p21, and BMC of pelvis on chromosome 20q12 and total body on 14q22-23 (logarithm of odds score > 3). We found genome-wide significant association between BMC of right arm and rs762920 at PVALB (P = 4.6 × 10-8), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 × 10-8). Exome-wide association analysis revealed novel association of variants at MEGF10 and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 × 10-7). CONCLUSIONS: We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. These findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation.

Bisphosphonate use in acute and chronic spinal cord injury: a systematic review.

BACKGROUND/OBJECTIVE: Bone density loss occurs rapidly after traumatic spinal cord injury (SCI) and is associated with low-energy fractures below the level of injury, commonly occurring around the knee. Bisphosphonates have been tested as potential agents to prevent bone loss after SCI, but no guidelines exist for clinical use of bisphosphonates in these patients. The objective of this study was to systematically review and evaluate evidence quality in studies of bisphosphonate use in patients with post-treatment follow-up of sublesional bone mineral density. METHODS: Literature search in MEDLINE/PubMed and ISI database using key words bisphosphonates, spinal cord injury, quadriplegia, paraplegia, and tetraplegia. RESULTS: The search identified 6 experimental studies and 1 quasi-experimental study of bisphosphonate therapy in patients with acute and chronic SCI. The studies were small and of fair or poor quality, and none included fracture outcomes. Mild attenuation of bone density loss with acute administration of bisphosphonates after SCI was found at some measurement sites but was not always maintained during follow-up. CONCLUSIONS: Data were insufficient to recommend routine use of bisphosphonates for fracture prevention in these patients. Current studies are limited by heterogeneity of patient populations and outcome measures. Uniform bone density measurement sites with rigorous quality control and compliance monitoring are needed to improve reliability of outcomes. Future studies should address specific populations (acute or chronic SCI) and should assess fracture outcomes.

The use of active surveillance cultures in adult intensive care units to reduce methicillin-resistant Staphylococcus aureus-related morbidity, mortality, and costs: a systematic review.

Active surveillance cultures (ASCs) are universal or targeted microbiological screening cultures for patients admitted to a hospital. ASCs have been proposed to control the increasing numbers of infections due to multidrug-resistant organisms, but their efficacy and cost-effectiveness are unproven. We conducted a systematic review of the literature pertaining to the use of ASCs and control of methicillin-resistant Staphylococcus aureus (MRSA). We searched relevant journals and the PubMed Medline, Web of Science, CINAHL, and Cochrane Library databases. No randomized, controlled trials were identified. Sixteen observational studies and 4 economic analyses were reviewed. Only 2 of the observational studies had a control group. None of the studies were of good quality. Thus, we identified important gaps in the literature, including a need for a clear definition of ASCs, a clear implementation protocol, and rigorous economic evaluations. Existing evidence may favor the use of ASCs, but the evidence is of poor quality, and definitive recommendations cannot be made.

Time to Clinically Relevant Fracture Risk Scores in Postmenopausal Women.

BACKGROUND: Clinical practice guidelines recommend use of fracture risk scores for screening and pharmacologic treatment decisions. The timing of occurrence of treatment-level (according to 2014 National Osteoporosis Foundation guidelines) or screening-level (according to 2011 US Preventive Services Task Force guidelines) fracture risk scores has not been estimated in postmenopausal women. METHODS: We conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores in postmenopausal women aged 50 years and older, prior to receipt of pharmacologic treatment and prior to first hip or clinical vertebral fracture. RESULTS: In 54,280 postmenopausal women aged 50 to 64 years without a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of rare incidence of treatment-level scores. In 6096 women who had FRAX scores calculated with bone mineral density, the estimated unadjusted time to treatment-level FRAX ranged from 7.6 years (95% confidence interval [CI], 6.6-8.7) for those aged 65 to 69, to 5.1 years (95% CI, 3.5-7.5) for those aged 75 to 79 at baseline. Of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years. CONCLUSIONS: Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.

Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study.

Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated. INTRODUCTION: We compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality. METHODS: A comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline. RESULTS: Among risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P < 0.0001). Calibration was good for the internally generated BMD T score predictor with or without age and poor for the externally developed risk tools. CONCLUSION: In untreated older men without fragility fractures at baseline, an age plus femoral neck BMD T score classifier identified men with incident hip fracture as accurately as more complicated fracture risk scores.

Correction to: Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study.

Owing to an oversight by the authors, the acknowledgments were incomplete.

Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study.

To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long-term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research.

Survey of osteoporosis preventive care in community family medicine settings.

OBJECTIVE: This study's objective was to document and describe osteoporosis preventive care for women age 45 years and older in community family medicine practices. METHODS: We conducted a crosssectional mailed survey of 400 women age 45 years and older enrolled in a community-based family medicine research network. Participants responded to 42 items regarding osteoporosis screening and prevention during primary care visits. RESULTS: A total of 275 women returned the survey (response rate 71.4%). Of the respondents, 162 (58.9% of the sample) were ages 45 to 64, and 113 (41.1%) were age 65 and older. Rates of counseling on calcium intake, exercise, falls, and bone density testing were similar in the two age groups. Half of women age 65 and older and 43.8% of women under 65 had received bone density testing. Ninety-two percent of the respondents rated a discussion of osteoporosis and fracture prevention with their primary care provider as "very," "moderately," or "somewhat" important, but only 44% actually had such a discussion. CONCLUSIONS: Most women age 45 and older considered osteoporosis preventive care to be important. However, fewer than half discussed this topic with their primary care provider, and only half of women age 65 and older had undergone bone density screening.