Technology trends in practice: A survey of occupational therapy practitioners.

BACKGROUND: Given the evolving digital revolution, technology and digital tools are becoming inseparable from work and daily occupations. Occupational therapy practitioners (OTPs) focus on supporting individuals in their desired and needed activities. Many of these daily activities (i.e., online banking, shopping, social media, smartphone use) require digital skills at a growing rate, and insufficient technological skills may subject individuals to limited engagement and social isolation. OBJECTIVE: To understand OTPs attitudes regarding technology utilization. METHODS: We surveyed 109 OTPs about their attitudes, work practices, and barriers to addressing their clients' digital technological functioning. RESULTS: The findings of our study suggest that while OTPs acknowledge the importance and potential benefit of technology for their clients, there is a notable professional gap in the training and skills of OTPs to support their clients' digital functioning effectively and to integrate technology into their practice. CONCLUSIONS: There is a need to improve and expand OTP's digital skills and knowledge regarding addressing clients' digital functioning and technology implementation in occupational therapy practice.

Uncovering the Obstacles-A Typology of Environmental and Contextual Factors Affecting Occupational Participation: A Scoping Review.

IMPORTANCE: Environmental and contextual factors may facilitate or limit participation in daily activities. A detailed, systematic categorization of such factors enhances evaluation and intervention and promotes occupational engagement. OBJECTIVE: To develop an inclusive, detailed, and comprehensive typology of terms for environmental and contextual factors that affect occupational engagement and participation. DATA SOURCES: We searched the Avery Index of Architectural Periodicals, ERIC, EMBASE, CINAHL, MEDLINE, Google Scholar, and Engineering Village databases, using the keywords environment, factors, context, participation, people, disability, disabilities, aspects, barriers, assessment, and evaluation. STUDY SELECTION AND DATA COLLECTION: Using Arksey and O'Malley's scoping review methodology, two reviewers screened and selected publications describing specific aspects of environmental and contextual factors that facilitate or diminish human occupational engagement or participation. FINDINGS: Forty-three articles and two book chapters published in English between 1997 and 2020 met the inclusion criteria. Terms extracted from this literature were iteratively screened and categorized. The resulting typology is organized into four areas with 12 categories and 53 specific terms. The typology's terms allow more fine-grained analysis of environmental factors described in the Occupational Therapy Practice Framework: Domain and Process (4th ed.) and the International Classification of Functioning, Disability and Health. CONCLUSIONS AND RELEVANCE: This typology provides occupational therapy practitioners with detailed language to identify, assess, intervene with, and research environmental and contextual factors that affect participation and participation choices of individuals, groups, and populations. What This Article Adds: The typology provides a comprehensive terminology for occupational therapy professionals and students to use, assess, and intervene at the environmental and contextual levels, thereby facilitating participation for more people.

Does it work? Using a Meta-Impact score to examine global effects in quasi-experimental intervention studies.

The evaluation of applied psychological interventions in the workplace or elsewhere is challenging. Randomisation and matching are difficult to achieve and this often results in substantial heterogeneity within intervention and control groups. As a result, traditional comparison of group means using null hypothesis significance testing may mask effects experienced by some participants. Using longitudinal studies of coaching interventions designed to provide support for dyslexic employees, this study describes and evaluates a different approach using a Meta-Impact score. We offer a conceptual rationale for our method, illustrate how this score is calculated and analysed, and show how it highlights person-specific variations in how participants react and respond to interventions. We argue that Meta-Impact is an incremental supplement to traditional variable-centric group-wise comparisons and can more accurately demonstrate in practice the extent to which an intervention worked. Such methods are needed for applied research, where personalized intervention protocols may require impact analysis for policy, legal and ethical purposes, despite modest sample sizes.

Intersectional Stigma for Autistic People at Work: A Compound Adverse Impact Effect on Labor Force Participation and Experiences of Belonging.

Background: Little research addresses the experiences of autistic people at work, yet employment prospects remain bleak. The extant literature takes a largely remedial perspective and does not focus on harnessing this population's considerable talents. In global organizational practice, several programs purposefully target autistic people for their abilities. However, preliminary evidence suggests that such programs are inadvertently attracting mainly White males, to the exclusion of other demographics. Therefore, stigma surrounding autism at work remains, creating potential compound adverse impacts by marginalizing identities, including gender, race, ethnicity, sexuality, and socioeconomic status. We explored the intersection of autism with other marginalizing identities in the context of work. The research focused on labor force participation for autistic people and, for those in employment, perceptions of exclusion and inclusion. We compared the aforementioned variables by gender identity, racial identity, sexuality, socioeconomic background, and geographic origin. Methods: We undertook a global cross-sectional survey, advertised through various social media platforms and promoted directly to relevant organizations. The survey included a range of validated measures as well as demographic information. We analyzed the data with frequencies, cross tabulations, chi-square tests, and non-parametric, group-wise comparisons. Results: We found preliminary evidence of reduced rates of employment participation by race and geographic location. Females and non-binary people had lower perceptions of inclusion and belonging at work. The perception of accommodation provision had a strong association with inclusion and belonging; more so than incidental provision of flexibility in environment and scheduling not framed as a specific accommodation. Conclusions: The findings highlight the relational aspects of accommodation and a more universal inclusion perspective. We urge practitioners and researchers to monitor employment participation and levels of inclusion/exclusion using intersectional demographic identification. We appeal for cross-cultural collaboration with academic institutions outside the anglosphere to improve our knowledge of global programs and their impact.

Why is this an important issue?: Employment data show that autistic people find it harder to get and keep work. This study focuses on understanding whether multiple identities and people's background make a difference. What is the purpose of this study?: We asked a group of Autistic people about gender and race, as well as being gay lesbian, bisexual, transgender or queer (LGBTQ). We asked where people live, their education, parents' education and whether they had any diagnoses in addition to autism. We predicted that these things would have a negative effect on autistic employment rates. We thought they would also affect how autistic people felt at work. What we did?: An online survey was completed by 576 autistic people. We analyzed whether their identities and backgrounds made it more or less likely that they were in work. We then asked the 387 employed people within this group about their experiences at work. We compared their experiences by identity and background to see whether these made a positive or negative difference. What we found?: We found that White Autistic people living in western countries such as the United States and Europe were more likely to have jobs. They were also more likely to have jobs specifically designed for Autistic people. We found that women, non-binary, and transgender autistic people felt less included at work. We also found that feeling that someone cares is more important than any adjustments to work scheduling such as flexible working to support people. What do these findings add to what was already known?: It is already known that autistic people are less likely to be in work than non-autistic people. This study shows that these overall numbers are masking important differences arising from gender, race, and ethnicity. What are the potential weaknesses in the study?: The survey was taken at one point in time, which does not explain how these differences happened. Most people who completed the study were highly educated. We did not have enough people from the non-western countries or communities of color. Therefore, the sample is not large or diverse enough to draw firm conclusions. How will the study help Autistic people now or in the future?: We hope that the study inspires people to think about different identities and additional stigma for autism at work programs. We have provided a sample of baseline data from all over the world that shows a difference by location. Even though this is just a trend, it might spark more research looking at the crossover between autism, identities, and backgrounds. It provides a starting point to help researchers who want to do longer studies that test interventions to improve autistic participation and experiences in work.

Evaluating the toxicity of escalating dose of oral picolinic acid in Sprague-Dawley rats.

Picolinic acid (PIC) is a byproduct of tryptophan catabolism through the kynurenine pathway, with anabolic effects on bone in vivo and in vitro. Hence, PIC has been nominated as a possible candidate to treat and/or prevent osteoporosis. However, the effective dose and toxicity of PIC are not known yet. To test the effect of escalating and very high doses of oral PIC, male Sprague-Dawley rats were gavaged PIC: Group 1 (n = 3) received incremental doses of 125, 250 and 500 mg/kg/day PIC on days 1, 3 and 5. Group 2 (n = 3) received 500 mg/kg BID (8 h apart; i.e. 1000 mg/kg/day) PIC on Day 1. Group 3 (n = 3) received 125 mg/kg/day PIC for seven consecutive days. Group 4 (n = 3) received 250 mg/kg/day PIC for seven consecutive days. Groups 1, 3 and 4 rats were euthanized on Day 8. Group 5 (n = 6) received 500 mg/kg/day PIC for two consecutive days and then once a week dose (Days 9, 16 and 23) of 500 mg/kg/dose PIC, until euthanasia (Day 30). Blood and cerebrospinal fluid (CSF) were sampled at euthanasia, and tissues showing abnormalities at necropsy underwent histopathology evaluation. All rats displayed some degree of mild hypercalcemia and hyperkalemia. Rats receiving high doses (500 or 1000 mg/kg/day) of PIC died or were euthanized on humane grounds within the first week after showing clinical neurological signs, with animals later revealed to have brain necrosis and hemorrhage at histopathology. Rats receiving lower doses (125 or 250 mg/kg/day) of PIC completed treatment course without apparent clinical adverse events. In summary, very high doses of PIC (≥500 mg/kg/day) were vascular-neurotoxic. Possible future experiments must consider significantly lower doses.

Failure of Healthcare Provision for Attention-Deficit/Hyperactivity Disorder in the United Kingdom: A Consensus Statement.

Background: Despite evidence-based national guidelines for ADHD in the United Kingdom (UK), ADHD is under-identified, under-diagnosed, and under-treated. Many seeking help for ADHD face prejudice, long waiting lists, and patchy or unavailable services, and are turning to service-user support groups and/or private healthcare for help. Methods: A group of UK experts representing clinical and healthcare providers from public and private healthcare, academia, ADHD patient groups, educational, and occupational specialists, met to discuss shortfalls in ADHD service provision in the UK. Discussions explored causes of under-diagnosis, examined biases operating across referral, diagnosis and treatment, together with recommendations for resolving these matters. Results: Cultural and structural barriers operate at all levels of the healthcare system, resulting in a de-prioritization of ADHD. Services for ADHD are insufficient in many regions, and problems with service provision have intensified as a result of the response to the COVID-19 pandemic. Research has established a range of adverse outcomes of untreated ADHD, and associated long-term personal, social, health and economic costs are high. The consensus group called for training of professionals who come into contact with people with ADHD, increased funding, commissioning and monitoring to improve service provision, and streamlined communication between health services to support better outcomes for people with ADHD. Conclusions: Evidence-based national clinical guidelines for ADHD are not being met. People with ADHD should have access to healthcare free from discrimination, and in line with their legal rights. UK Governments and clinical and regulatory bodies must act urgently on this important public health issue.

Characterization of an Acute Rodent Osteomyelitis Infectious Model Using a Tibial Intramedullary Implant Inoculation.

Chronic osteomyelitis in presence of orthopedic implants is a condition observed in the field of biomaterials as it impairs early bone-implant contact, fixation and integration. In this study, a surgical intramedullary tibial insertion was performed using a titanium wire previously inoculated with Staphylococcus aureus in order to develop an osteomyelitis model in a clinically relevant long bone and in absence of any prophylactic treatment. As such, twenty-two male Sprague-Dawley rats received a sterile or inoculated intramedullary biomaterial with either 2 × 106 or 1 × 107 S. aureus colony forming units. Bacterial burden, inflammation, morphological changes, as well as newly formed bone tissues were evaluated for histopathology following a period of either eight or fifteen days of implantation. The implant inoculated in presence of the highest bacterial load was effective to produce significant periprosthetic infection observations in addition to hard and soft tissue inflammation consistent with the development of osteomyelitis. In contrast, neither the sterile nor the low-dose implant inoculation showed inflammation and clinical infection signs, but rather produced an expected bone remodeling and appropriate healing associated with biomaterial implantation. Complete health assessment is presented with histopathological periprosthetic results.

Neurodiversity at work: a biopsychosocial model and the impact on working adults.

INTRODUCTION: The term neurodiversity is defined and discussed from the perspectives of neuroscience, psychology and campaigners with lived experience, illustrating the development of aetiological theories for included neurodevelopmental disorders. The emerging discourse is discussed with relevance to adults, social inclusion, occupational performance and the legislative obligations of organizations. SOURCES OF DATA: Literature is reviewed from medicine, psychiatry, psychology, sociology and popular press. No new data are presented in this article. AREAS OF AGREEMENT: There is consensus regarding some neurodevelopmental conditions being classed as neurominorities, with a 'spiky profile' of executive functions difficulties juxtaposed against neurocognitive strengths as a defining characteristic. AREAS OF CONTROVERSY: The developing nomenclature is debated and the application of disability status versus naturally occurring difference. Diagnosis and legal protections vary geographically, resulting in heretofore unclear guidance for practitioners and employers. GROWING POINTS: The evolutionary critique of the medical model, recognizing and updating clinical approaches considering the emerging consensus and paradigmatic shift. AREAS TIMELY FOR DEVELOPING RESEARCH: It is recommended that research addresses more functional, occupational concerns and includes the experiences of stakeholders in research development, moving away from diagnosis and deficit towards multi-disciplinary collaboration within a biopsychosocial model.

The Impact of Infusion Center Layout on Workflow and Satisfactions in Two Cancer Infusion Centers: A Case Study on Staff and Patients.

OBJECTIVE: The objective of this empirical research is to compare nurses' operational workflow and nurses' and patients' satisfactions of two different infusion center designs. One center has a traditional open bay design and the other has semi-private bays. This study also intends to gather baseline data to compare to a future post-occupancy evaluation of a new infusion center where the two existing centers will be combined. BACKGROUND: The increasing number of patients with cancer diagnosis who refer to infusion centers highlights the importance of design of these centers. METHOD: The mixed-method approach of this study involves shadowing nurses and surveying nurses and patients. Data collection captured nurses' activities, activity durations, and nurses' and patients' satisfaction with the design of clinics. RESULTS: Comparison of shadowing data indicated that although the infusion centers have different layouts, there are no significant differences in the activities or time spent by nurses in different areas among the centers. Staff, however, have different satisfaction levels with visual and speech privacy, ability to concentrate without distraction, collaboration with other staff, and the process of medication delivery. Patients also had slightly different satisfaction levels with their ability to communicate with staff and design of bays. CONCLUSION: This research sheds light on operational workflows and satisfaction of staff and patients in two different infusion center design. Considering the limited studies on these settings, this study serves as baseline data to compare to other studies on cancer infusion centers and addresses issues of benchmarking and staff and patient satisfaction.

A Thematic Analysis Investigating the Impact of Positive Behavioral Support Training on the Lives of Service Providers: "It Makes You Think Differently".

Positive behavioral support (PBS) employs applied behavioral analysis to enhance the quality of life of people who behave in challenging ways. PBS builds on the straightforward and intuitively appealing notion that if people know how to control their environments, they will have less need to behave in challenging ways. Accordingly, PBS focuses on the perspective of those who have behavioral issues, and assesses success via reduction in incidences of challenging behaviors. The qualitative research presented in this report approaches PBS from a different viewpoint and, using thematic analysis, considers the impact of PBS training on the lived experience of staff who deliver services. Thirteen support staff who work for a company supplying social care and supported living services for people with learning disabilities and complex needs in the northwest of England took part. Analysis of interviews identified five major themes. These were: (1) training: enjoyable and useful; (2) widening of perspective: different ways of thinking; (3) increased competence: better outcomes; (4) spill over into private lives: increased tolerance in relationships; and (5) reflecting on practice and moving to a holistic view: "I am aware that people…are not just being naughty." These themes evidenced personal growth on the part of service providers receiving training. Explicitly, they demonstrated that greater awareness of PBS equipped recipients with an appropriate set of values, and the technical knowledge required to realize them.

Context matters: A review to formulate a conceptual framework for coaching as a disability accommodation.

Although dyslexia affects 5-8% of the workforce this developmental disorder has not been sufficiently researched in adult populations. Yet a diagnosis confers legal protections as employers must provide disability 'accommodations' to assist work functioning and performance. The implementation of such accommodations, including coaching, lacks theoretical framing and evaluations of impact in practice. Recognizing a need for conceptual work, we undertook a narrative, systematic scoping review from a realist pragmatic epistemology, taking an iterative approach to define and address the review question: 'to what extent, and under what conditions, can face-to-face learning interventions improve Working Memory (WM) and Self-Efficacy (SE) and can these lead to functional improvements related to work performance?' Informed by expert and stakeholder consultation and user data, our review extracted and synthesized 25 studies from eleven countries to identify potentially applicable learning intervention theories, their effects upon WM and SE but also functional outcomes such as comprehension. We suggest that intervention protocols informed by Social Cognitive Learning Theory can improve SE, as would be expected, and more surprisingly also WM. The development of metacognition, stress management and fidelity to Goal Setting Theory were identified as valuable intervention features. We propose that coaching activities may provide a more contextualized environment for transfer of learning from WM to functional skills such as comprehension, when compared to computerized training interventions. We call for theoretically underpinned, primary studies to evaluate interventions with adult dyslexic populations to further our understanding of disability accommodations.

Scoping review of mentoring research in the occupational therapy literature, 2002-2018.

INTRODUCTION: Mentoring affords personalised learning for professional growth. Research across disciplines has shown mentoring to positively affect behaviour, attitude, motivation, job performance, organisational commitment, and career productivity and success. This study was conducted to provide an overview of research focussed on mentoring practices and related outcomes specific to the occupational therapy profession. METHODS: This study follows Arksey and O'Malley's five main scoping review stages. PubMed, Embase, CINAHL, PsycINFO, Web of Science, ERIC, Social Services Abstract, ScienceDirect and ProQuest databases were searched for mentoring practices in the occupational therapy profession. Inclusion criteria were: empirical studies of mentoring provided to occupational therapy students, practitioners, faculty and researchers, published in English between January 2002 and December 2018. Studies of mentoring provided to occupational therapy clients were excluded. Data were extracted for quantitative information about study characteristics and qualitative information about mentoring processes and outcomes. RESULTS: Of 1313 retrieved resources, 20 empirical studies were selected for analysis. In these studies, occupational therapy entry-level students, post-professional students, educators, researchers and clinicians were mentored in education, research and clinical areas of practice. Mentoring definitions, rationale, approaches and measurement methods were varied. Mentoring processes and relationships were facilitated by mechanisms of creating a plan, using mentoring strategies and providing support. Common defining terms, mechanisms and outcomes of mentoring were extracted and categorised into: support, learning, process and relationship. Mentoring outcomes were related to knowledge acquisition and translation, professional behaviours, increased productivity and professional networking. CONCLUSION: This scoping review presented commonalities of mentoring definitions, mechanisms and outcomes in empirically studied mentoring experiences and programmes in the occupational therapy profession. Methodological gaps in this research emphasise the need for occupational therapy practitioners and researchers to continue researching mentoring experiences by integrating theoretical frameworks, uniform definitions, rigorous design and standardised measures to evaluate the effectiveness of mentoring.

Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in Ovariectomized Cynomolgus Monkeys.

Romosozumab (Romo), a humanized sclerostin antibody, is a bone-forming agent under development for treatment of osteoporosis. To examine the effects of Romo on bone quality, mature cynomolgus monkeys (cynos) were treated 4 months post- ovariectomy (OVX) with vehicle, 3 mg/kg, or 30 mg/kg Romo for 12 months, or with 30 mg/kg Romo for 6 months followed by vehicle for 6 months (30/0). Serum bone formation markers were increased by Romo during the first 6 months, corresponding to increased cancellous, endocortical, and periosteal bone formation in rib and iliac biopsies at months 3 and 6. Dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) was increased by 14% to 26% at the lumbar spine and proximal femur at month 12, corresponding to significant increases in bone strength at 3 and 30 mg/kg in lumbar vertebral bodies and cancellous cores, and at 30 mg/kg in the femur diaphysis and neck. Bone mass remained positively correlated with strength at these sites, with no changes in calculated material properties at cortical sites. These bone-quality measures were also maintained in the 30/0 group, despite a gradual loss of accrued bone mass. Normal bone mineralization was confirmed by histomorphometry and ash analyses. At the radial diaphysis, a transient, reversible 2% reduction in cortical BMD was observed with Romo at month 6, despite relative improvements in bone mineral content (BMC). High-resolution pQCT confirmed this decline in cortical BMD at the radial diaphysis and metaphysis in a second set of OVX cynos administered 3 mg/kg Romo for 6 months. Radial diaphyseal strength was maintained and metaphyseal strength improved with Romo as estimated by finite element modeling. Decreased radial cortical BMD was a consequence of increased intracortical remodeling, with no increase in cortical porosity. Romo resulted in marked improvements in bone mass, architecture, and bone strength, while maintaining bone quality in OVX cynos, supporting its bone efficacy and safety profile. © 2016 American Society for Bone and Mineral Research.

Faculty Mentors' Perspectives on E-Mentoring Post-Professional Occupational Therapy Doctoral Students.

E-mentoring is a viable option for mentoring students in occupational therapy educational programs. The objective of this study was to investigate faculty perspectives of faculty-to-student e-mentoring in an online post-professional doctor of occupational therapy program. In a retrospective mixed-method design, nine faculty members described features and outcomes of e-mentoring 48 doctoral students. Online survey results were analysed quantitatively for descriptive statistics; transcripts from structured interviews were analysed using qualitative content analysis. The results showed that successful, satisfactory e-mentoring is student-centered, flexible, frequent, academically and psychosocially supportive; faculty members must be skilled in adapting e-mentoring to the needs and objectives of each mentee; e-mentoring provides opportunities for faculty members and students to achieve academic and professional objectives and growth. The findings suggest that implementation of e-mentoring may be a useful model in other occupational therapy programs. There is a need for future studies with broader participant pool, observable measures of e-mentoring, standardized measures of satisfaction and success and comparison between e-mentoring with and without web camera. Copyright © 2016 John Wiley & Sons, Ltd.

Use of an Electron Beam Melting Manufactured Titanium Collared Cementless Femoral Stem to Resist Subsidence After Canine Total Hip Replacement.

OBJECTIVES: To evaluate the effect of a collared electron beam melting (EBM)-manufactured titanium cementless femoral stem on implant subsidence after total hip replacement (THR). STUDY DESIGN: Prospective study ANIMALS: Dogs (n = 26); 33 THR. METHODS: Records were maintained on the first 110 consecutive THR using an EBM collared femoral stem. Radiographs on the first 33 THR that had 6-months follow-up were evaluated for implant subsidence. These results were compared to 27 dogs with subsidence after THR with a Co Cr collarless stem. RESULTS: Dogs that had EBM collared stem THR had a mean body weight of 35.4 kg, body condition score (BCS) of 6.21, and mean canal flare index (CFI) of 1.56. EBM stem sizes used (number implanted) were #7 (13), #8 (10), #9 (8), and #10 (2). Subsidence of collared stems did not occur if the collar was in contact with cortical bone during surgery. Subsidence of 1-3 mm occurred closing a gap between the collar and bone if contact was not made during surgery, but subsidence stopped once contact was made. No major complications directly related to the EBM collared stem were encountered. CONCLUSIONS: A collar on a cementless femoral stem in contact with cortical bone resists subsidence.

The nature, perception, and impact of e-mentoring on post-professional occupational therapy doctoral students.

This retrospective study employed a descriptive, quantitative design to investigate the nature, perception, and impact of the e-mentoring experiences of 29 graduates of an online post-professional Doctor of Occupational Therapy (OTD) program. Study results highlight positive features of electronic mentoring (e-mentoring); how multi-modal e-mentoring supports the accessibility needs of participants; and students' preferences to engage in real-time e-mentoring communication by web camera or telephone, supplemented with e-mail. E-mentoring positively impacted the professional development of participants during and after the online OTD program. As online education continues to grow, a better understanding of e-mentoring will assist in providing exemplary education to meet the needs of adult learners.

Physical rehabilitation after total joint arthroplasty in companion animals.

Patients who have total joint arthroplasty have varying needs related to rehabilitation. In the short term, rehabilitation should be used in all dogs to identify high-risk patients and to minimize the likelihood of postoperative complications. Many patients undergoing total hip replacement recover uneventfully without needing long-term physiotherapy. All patients undergoing total knee replacement and total elbow replacement need rehabilitation to restore limb use and maximize their functional recovery. This article presents rehabilitation considerations for companion animals undergoing total hip replacement, total knee replacement, and total elbow replacement; postoperative complications and how to mitigate risks; and anticipated patient outcomes.

Long-term treatment with eldecalcitol (1α, 25-dihydroxy-2ß- (3-hydroxypropyloxy) vitamin D3) suppresses bone turnover and leads to prevention of bone loss and bone fragility in ovariectomized rats.

The purpose of this study is to estimate the efficacy of eldecalcitol (1α, 25-Dihydroxy-2ß- (3-hydroxypropyloxy) vitamin D3; ELD) on bone metabolism after long-term administration. Six-month-old Wistar-Imamichi rats were ovariectomized (OVX) and administered ELD orally at doses of 7.5, 15, or 30 ng/kg daily. Bone mineral density (BMD), urinary excretion of deoxypyridinoline (DPD), a bone resorption marker, and serum total alkaline phosphatase (ALP), a surrogate marker of bone formation, were assessed after 3, 6, and 12 months of treatment. After 12 months of treatment, the biomechanical strength of the L4 lumbar vertebra and femoral shaft was measured, and bone histomorphometry was performed on the L3 lumbar vertebra and the tibia diaphysis. ELD prevented OVX-induced decreases in BMD of the lumbar vertebrae and femur throughout the treatment period. ELD significantly suppressed OVX-induced increases in urinary DPD excretion throughout the treatment period with minimal effects on ALP. OVX resulted in significant decreases in ultimate load and stiffness of the L4 lumbar vertebra and femoral shaft, and ELD significantly prevented the reduction in these biomechanical parameters. Bone histomorphometry at the L3 lumbar vertebra revealed that OVX induced increases in bone resorption parameters (osteoclast surface and osteoclast number) and bone formation parameters (osteoblast surface, osteoid surface, and bone formation rate), and ELD suppressed these parameters after 12 months treatment. Activation frequency, which was elevated in the OVX/vehicle group, was significantly suppressed to baseline levels in ELD-treated groups, indicating that ELD maintained bone turnover at a normal level. ELD also prevented OVX-induced deterioration of microstructure in trabecular and cortical bone. These results indicated that long-term treatment of OVX rats with ELD suppressed bone turnover, and prevented OVX-induced bone loss, deterioration of bone microstructure, and reduction in bone biomechanical strength.

Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality.

Eldecalcitol, a vitamin D analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.

Vitamin D insufficiency is common in elderly people worldwide, and intake of supplementary calcium and vitamin D is recommended to those with a high risk of fracture. Several clinical studies and meta-analyses have shown that calcium and vitamin D supplementation reduces osteoporotic fractures, and a strong correlation exists between vitamin D status and fracture risk. Vitamin D supplementations improve calcium balance in the body; however, it remains unclear whether vitamin D directly affects bone metabolism. Recently, eldecalcitol (ELD), an active form of vitamin D analog, has been approved for the treatment of osteoporosis in Japan. A 3-year clinical trial showed ELD treatment increased lumbar spine bone mineral density (BMD) and reduced fracture risk in patients with osteoporosis. To evaluate the mechanism of ELD action in bone remodeling, ovariectomized cynomolgus monkeys were treated with 0.1 or 0.3µg/day of ELD for 6months. This treatment increased lumbar BMD by 4.4% and 10.2%, respectively, and suppressed ovariectomy-induced increases in bone turnover markers compared to OVX-vehicle control. Histomorphometric analysis of bone revealed that both bone formation parameters and bone resorption parameters in the trabecular bone of the lumbar vertebrae were suppressed by ELD treatment. ELD treatment also improved biomechanical properties of the lumbar vertebrae and the femoral neck in the ovariectomized cynomolgus monkeys. These results indicate that, in a bone-remodeling animal model, ELD increases BMD and improves bone biomechanical properties by normalizing bone turnover. Therefore, ELD has a direct and potentially beneficial effect on bone metabolism.