If you don’t take it – it can’t work: the consequences of not being treated or nonadherence to osteoporosis therapy

Osteoporosis is a growing problem worldwide, linked to an increasingly aging population. Despite the availability of a wide variety of treatments for osteoporosis, a significant number of patients are either not being prescribed treatment or discontinue therapy as early as 6 months after initiation. The reasons for a lack of adherence are many but poor adherence increases the risk of fracture and, therefore, the disease burden to the patient and society. Results from large-scale, randomized clinical studies have shown that different osteoporosis treatments are efficacious in reducing the risk of fracture. Studies assessing the effects of discontinuing osteoporosis therapies show that some treatments appear to continue to protect patients from the risk of future fracture even when treatment is stopped. However, these trials involve patients who have been compliant with treatment for between 2 and 5 years, a situation not reflective of real-world clinical practice. In reality, patients who discontinue therapy within the first 6 months may never achieve the optimum protection from fracture regardless of which treatment they have been prescribed. Clinicians need to develop management strategies to enable patients to adhere to their treatment. This will ultimately result in better prevention of fracture and a lower burden of disease to society and patients

Evaluation of easily measured risk factors in the prediction of osteoporotic fractures

BACKGROUND: Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. METHODS: Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (<65, 65–69, 70–74, 75–79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, ≥ 57kg), maternal history of hip facture (yes, no), prior fracture after age 50 (yes, no), hip T-score (>-1, -1 to >-2.5, ≤-2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. RESULTS: The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75–79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip facture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). CONCLUSION: This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice

A Scoping Review of Strategies for the Prevention of Hip Fracture in Elderly Nursing Home Residents

Elderly nursing home residents are at increased risk of hip fracture; however, the efficacy of fracture prevention strategies in this population is unclear.We performed a scoping review of randomized controlled trials of interventions tested in the long-term care (LTC) setting, examining hip fracture outcomes.We searched for citations in 6 respective electronic searches, supplemented by hand searches. Two reviewers independently reviewed all citations and full-text papers; consensus was achieved on final inclusion. Data was abstracted in duplicate.We reviewed 22,349 abstracts or citations and 949 full-text papers. Data from 20 trials were included: 7--vitamin D (n = 12,875 participants), 2--sunlight exposure (n = 522), 1--alendronate (n = 327), 1--fluoride (n = 460), 4--exercise or multimodal interventions (n = 8,165), and 5--hip protectors (n = 2,594). Vitamin D, particularly vitamin D(3) > or = 800 IU orally daily, reduced hip fracture risk. Hip protectors reduced hip fractures in included studies, although a recent large study not meeting inclusion criteria was negative. Fluoride and sunlight exposure did not significantly reduce hip fractures. Falls were reduced in three studies of exercise or multimodal interventions, with one study suggesting reduced hip fractures in a secondary analysis. A staff education and risk assessment strategy did not significantly reduce falls or hip fractures. In a study underpowered for fracture outcomes, alendronate did not significantly reduce hip fractures in LTC.The intervention with the strongest evidence for reduction of hip fractures in LTC is Vitamin D supplementation; more research on other interventions is needed

Inter-model comparison of global hydroxyl radical (OH) distributions and their impact on atmospheric methane over the 2000–2016 period

The modeling study presented here aims to estimate how uncertainties in global hydroxyl radical (OH) distributions, variability, and trends may contribute to resolving discrepancies between simulated and observed methane (CH4) changes since 2000. A multi-model ensemble of 14 OH fields was analyzed and aggregated into 64 scenarios to force the offline atmospheric chemistry transport model LMDz (Laboratoire de Meteorologie Dynamique) with a standard CH4 emission scenario over the period 2000–2016. The multi-model simulated global volume-weighted tropospheric mean OH concentration ([OH]) averaged over 2000–2010 ranges between 8:7*10^5 and 12:8*10^5 molec cm-3. The inter-model differences in tropospheric OH burden and vertical distributions are mainly determined by the differences in the nitrogen oxide (NO) distributions, while the spatial discrepancies between OH fields are mostly due to differences in natural emissions and volatile organic compound (VOC) chemistry. From 2000 to 2010, most simulated OH fields show an increase of 0.1–0:3*10^5 molec cm-3 in the tropospheric mean [OH], with year-to-year variations much smaller than during the historical period 1960–2000. Once ingested into the LMDz model, these OH changes translated into a 5 to 15 ppbv reduction in the CH4 mixing ratio in 2010, which represents 7%–20% of the model-simulated CH4 increase due to surface emissions. Between 2010 and 2016, the ensemble of simulations showed that OH changes could lead to a CH4 mixing ratio uncertainty of > 30 ppbv. Over the full 2000–2016 time period, using a common stateof- the-art but nonoptimized emission scenario, the impact of [OH] changes tested here can explain up to 54% of the gap between model simulations and observations. This result emphasizes the importance of better representing OH abundance and variations in CH4 forward simulations and emission optimizations performed by atmospheric inversions

Three-dimensional localization of ultracold atoms in an optical disordered potential

We report a study of three-dimensional (3D) localization of ultracold atoms suspended against gravity, and released in a 3D optical disordered potential with short correlation lengths in all directions. We observe density profiles composed of a steady localized part and a diffusive part. Our observations are compatible with the self-consistent theory of Anderson localization, taking into account the specific features of the experiment, and in particular the broad energy distribution of the atoms placed in the disordered potential. The localization we observe cannot be interpreted as trapping of particles with energy below the classical percolation threshold.Comment: published in Nature Physics; The present version is the initial manuscript (unchanged compared to version 1); The published version is available online at http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys2256.htm

An interdisciplinary knowledge translation intervention in long-term care: Study protocol for the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial

BACKGROUND: Knowledge translation (KT) research in long-term care (LTC) is still in its early stages. This protocol describes the evaluation of a multifaceted, interdisciplinary KT intervention aimed at integrating evidence-based osteoporosis and fracture prevention strategies into LTC care processes. METHODS AND DESIGN: The Vitamin D and Osteoporosis Study (ViDOS) is underway in 40 LTC homes (n = 19 intervention, n = 21 control) across Ontario, Canada. The primary objectives of this study are to assess the feasibility of delivering the KT intervention, and clinically, to increase the percent of LTC residents prescribed ≥800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced by our partner pharmacy provider and have more than one prescribing physician. The target audience within each LTC home is the Professional Advisory Committee (PAC), an interdisciplinary team who meets quarterly. The key elements of the intervention are three interactive educational sessions led by an expert opinion leader, action planning using a quality improvement cycle, audit and feedback reports, nominated internal champions, and reminders/point-of-care tools. Control homes do not receive any intervention, however both intervention and control homes received educational materials as part of the Ontario Osteoporosis Strategy. Primary outcomes are feasibility measures (recruitment, retention, attendance at educational sessions, action plan items identified and initiated, internal champions identified, performance reports provided and reviewed), and vitamin D (≥800 IU/daily) prescribing at 6 and 12 months. Secondary outcomes include the proportion of residents prescribed calcium supplements and osteoporosis medications, and falls and fractures. Qualitative methods will examine the experience of the LTC team with the KT intervention. Homes are centrally randomized to intervention and control groups in blocks of variable size using a computer generated allocation sequence. Randomization is stratified by home size and profit/nonprofit status. Prescribing data retrieval and analysis are performed by blinded personnel. DISCUSSION: Our study will contribute to an improved understanding of the feasibility and acceptability of a multifaceted intervention aimed at translating knowledge to LTC practitioners. Lessons learned from this study will be valuable in guiding future research and understanding the complexities of translating knowledge in LTC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01398527

A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged >= 60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with aT-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. (c) 2020 American Society for Bone and Mineral Research

The human patellar tendon moment arm assessed in vivo using dual-energy X-ray absorptiometry

Accurate assessment of muscle-tendon forces in vivo requires knowledge of the muscle-tendon moment arm. Dual-energy X-ray absorptiometry (DXA) can produce 2D images suitable for visualising both tendon and bone, thereby potentially allowing the moment arm to be measured but there is currently no validated DXA method for this purpose. The aims of this study were (i) to compare in vivo measurements of the patellar tendon moment arm (d) assessed from 2D DXA and magnetic resonance (MR) images and (ii) to compare the reliability of the two methods. Twelve healthy adults (mean±SD: 31.4±9.5yr; 174.0±9.5cm; 76.2±16.6kg) underwent two DXA and two MR scans of the fully extended knee at rest. The tibiofemoral contact point (TFCP) was used as the centre of joint rotation in both techniques, and the d was defined as the perpendicular distance from the patellar tendon axis to the TFCP. The d was consistently longer when assessed via DXA compared to MRI (+3.79±1.25mm or +9.78±3.31%; P<0.001). The test-retest reliability of the DXA [CV=2.13%; ICC=0.94; ratio limits of agreement (RLA)=1.01 (*/÷1.07)] and MR [(CV=2.27%; ICC=0.96; RLA=1.00 (*/÷1.07)] methods was very high and comparable between techniques. Moreover, the RLA between the mean DXA and MRI d values [1.097 (*/÷1.061)] demonstrated very strong agreement between the two methods. In conclusion, highly reproducible d measurements can be determined from DXA imaging with the knee fully extended at rest. This has implications for the calculation of patellar tendon forces in vivo where MR equipment is not available. © 2014 Elsevier Ltd

Bone morphogenetic proteins − 7 and − 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model

Background: Bone infections due to trauma and subsequent delayed or impaired fracture healing represent a great challenge in orthopedics and trauma surgery. The prevalence of such bacterial infection-related types of delayed non-union is high in complex fractures, particularly in open fractures with additional extensive soft-tissue damage. The aim of this study was to establish a rat model of delayed osseous union secondary to bacterial osteitis and investigate the impact of rhBMP-7 and rhBMP-2 on fracture healing in the situation of an ongoing infection. Methods: After randomization to four groups 72 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia stabilized by intramedullary titanium K-wires. Three groups received an intramedullary inoculation with Staphylococcus aureus (103 colony-forming units) before stabilization and the group without bacteria inoculation served as healing control. After 5 weeks, a second surgery was performed with irrigation of the medullary canal and local rhBMP-7 and rhBMP-2 treatment whereas control group and infected control group received sterile saline. After further 5 weeks rats were sacrificed and underwent biomechanical testing to assess the mechanical stability of the fractured bone. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, and to quantify callus formation and the mineralized area of the callus. Results: Biomechanical testing showed a significantly higher fracture torque in the non-infected control group and the infected rhBMP-7- and rhBMP-2 group compared with the infected control group (p &lt; 0.001). RhBMP-7 and rhBMP-2 groups did not show statistically significant differences (p = 0.57). Histological findings supported improved bone-healing after rhBMP treatment but quantitative micro-CT and histomorphometric results still showed significantly more hypertrophic callus tissue in all three infected groups compared to the non-infected group. Results from a semiquantitative bone-healing-score revealed best bone-healing in the non-infected control group. The expected chronic infection was confirmed in all infected groups. Conclusions: In delayed bone healing secondary to infection rhBMP treatment promotes bone healing with no significant differences in the healing efficacy of rhBMP-2 and rhBMP-7 being noted. Further new therapeutic bone substitutes should be analyzed with the present rat model for delayed osseous union secondary to bacterial osteitis