Prevention Of Fragility Fractures Research Articles

Novel Approach to Identify Patients With the Most to Gain From New Treatment Options Intended to Prevent Fragility Fractures.

Novel Approach to Identify Patients With the Most to Gain From New Treatment Options Intended to Prevent Fragility Fractures.

UK clinical guideline for the prevention and treatment of osteoporosis

SummaryThe National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management.IntroductionThe UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older.MethodsWhere available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence.ResultsReview of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement.ConclusionThe guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

Prevalence and influencing factors of spinal cord injury-related osteoporosis and fragility fractures in Thai people with chronic spinal cord injury: A cross-sectional, observational study

Objective To investigate the prevalence and influencing factors of spinal cord injury (SCI)-related osteoporosis and fragility fractures in Thai people with chronic spinal cord injury. Design A cross-sectional, observational study. Setting Outpatient clinic, Department of Rehabilitation Medicine, Maharaj Nakorn Chiang Mai Hospital. Participants Thais with chronic spinal cord injury (SCI) (duration of injury at least one year). Intervention Not applicable. Outcome measures Dual-energy X-ray absorptiometry (DXA) was performed to measure bone mineral density (BMD) at the hip. Analyses were performed to identify risk factors for SCI-related osteoporosis or fragility fracture development. Thai FRAX® score was calculated with and without BMD and compared for each participant. Results Among 64 Thais with chronic SCI, the prevalence of SCI-related osteoporosis was 43.8%. Female sex, non-ambulatory status, and at least 10 years duration of spinal cord injury increased the risk of having SCI-related osteoporosis. The prevalence of fragility fracture was 9.4%. Female sex, duration of SCI, and being diagnosed with SCI-related osteoporosis increased the risk of having a fragility fracture. Thai FRAX® score without BMD value underestimated the risk of prevalent fracture in 7.8% of participants. Conclusions SCI-related osteoporosis and fragility fractures are common in Thais with chronic SCI. Our findings emphasize the importance of SCI-related osteoporosis and fragility fracture surveillance in people with chronic SCI regardless of their ethnicity. FRAX® without BMD calculations could underestimate the risk of fragility fracture in people with chronic SCI. Therefore, further studies are needed to develop an SCI-specific fracture-risk assessment tool using risk factors proposed in previous studies and in this study.

Physical Therapist Management of Patients With Suspected or Confirmed Osteoporosis: A Clinical Practice Guideline From the Academy of Geriatric Physical Therapy.

A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development group (GDG) that was appointed by the Academy of Geriatric Physical Therapy (APTA Geriatrics). The GDG consisted of an exercise physiologist and 6 physical therapists with clinical and methodological expertise. The guideline was based on a systematic review of existing clinical practice guidelines, followed by application of the ADAPTE methodological process described by Guidelines International Network for adapting guidelines for cultural and professional utility. The recommendations contained in this guideline are derived from the 2021 Scottish Intercollegiate Guideline Network (SIGN) document: Management of Osteoporosis and the Prevention of Fragility Fractures. These guidelines are intended to assist physical therapists practicing in the United States, and implementation in the context of the US health care system is discussed.

Cost-Effectiveness Analysis of Fracture Liaison Services Compared with Standard of Care in the Secondary Prevention of Fragility Fractures in Spain.

PurposeTo assess the cost-effectiveness of a Fracture Liaison Service (FLS) compared with standard care for the secondary prevention of fragility fractures in Spain.MethodsPatients with osteoporosis and an initial fragility fracture who were candidates to initiate osteoporosis treatment (mean age 65 years, 90.7% female) were included in the model. Disease progression was simulated with a Markov model through seven health states (with and without osteoporosis treatment, subsequent hip, vertebral, forearm and humerus fracture, and death). A time horizon of 10 years and a 6-month duration per cycle was set. Clinical, economic, and quality of life parameters were estimated from the literature and Spanish clinical practice. Resource use and treatment patterns were validated by an expert panel. The Spanish National Health System (SNS) perspective was adopted, taking direct costs (€; 2020) into account. Effectiveness was measured in life-years gained (LYG) and quality-adjusted life years gained (QALYs). A discount rate of 3% was applied to costs and outcomes. The uncertainty of the parameters was assessed using deterministic, scenario and probabilistic sensitivity analyses (1000 iterations).ResultsSetting up a FLS for the secondary prevention of fragility fractures in Spain would provide better osteoporosis treatment initiation and persistence. This would reduce subsequent fragility fractures, disutilities and deaths. FLS would have greater clinical benefits (0.008 and 0.082 LYG and QALY gained per patient, respectively) and higher costs (€563.69 per patient) compared with standard care, leading to an incremental cost-utility ratio of €6855.23 per QALY gained over the 10 years horizon. The sensitivity analyses showed limited dispersion of the base case results, corroborating their robustness.ConclusionFrom the SNS perspective and considering Spanish willingness-to-pay thresholds, the introduction of FLS for the secondary prevention of fragility fractures would be a cost-effective strategy.

Assessing the Effectiveness of Bisphosphonates for the Prevention of Fragility Fractures: An Updated Systematic Review and Network Meta-Analyses.

ABSTRACTBisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta‐analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures (hazard ratio [HR] 0.38; 95% credibility interval [CrI], 0.28–0.49). Zoledronate (HR 0.71; 95% CrI, 0.61–0.81) and risedronate (HR 0.70; 95% CrI, 0.53–0.84) were found to be the most effective treatments in preventing nonvertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment mean difference (MD 4.02; 95% CrI, 3.2–4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost‐effectiveness, zoledronate could be considered a first‐line option for people at increased risk of fragility fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone Mineral Density Post a Spinal Cord Injury: A Review of the Current Literature Guidelines.

Background: Spinal cord injury (SCI) causes rapid osteoporosis below the level of injury in a multi-factorial manner. This literature review focused on the early diagnosis of low bone mass (LBM) in SCI patients and aimed to summarize all the available recent data on the diagnosis and treatment of osteoporosis in this unique patient population. Materials and Methods: Advanced literature research was conducted in the online PubMed database using the keywords 'bone mineral density, 'spinal cord injury, 'skeletal fragility', and 'osteoporotic fractures'. Out of the initial 430 articles, duplicates were removed and the remaining studies were assessed for eligibility. Two reviewers independently extracted data from each study and assessed variable reporting of outcome data. The exclusion criteria were: studies not measuring bone mineral density (BMD), studies comparing SCI to other diseases, animal studies, molecular studies, studies including children, and studies not written in English. The 83 remaining papers were divided into studies focusing on treatment and studies investigating LBM in SCI. Following this step, studies with small patient samples set at 20 patients with SCI for the treatment group and 30 patients for the diagnosis of the LBM group, were also excluded.Results: In the remaining 32 studies, 18 focused on the diagnosis of LBM in SCI and 14 focused on the various treatment options to address this phenomenon. Most of these studies (n=13) used the dual-energy X-ray absorptiometry (DXA) method to evaluate bone mass while five studies preferred quantitative computed tomography (QCT) measurements and one evaluated LBM using calcaneal qualitative ultrasound. In the treatment group of studies, seven papers administered medication to address LBM and four clinical protocols used physiotherapy methods to reduce bone loss post-SCI while three studies combined medical treatment with physiotherapy.Conclusion: The unawareness of the unique mechanism through which bone is rapidly lost in the first months post-SCI led to initial scientific confusion. In this review, we summarize information to increase physicians’ awareness of the dangers of ‘silent’ osteoporosis progression post-SCI. We have also provided information on the best timing to evaluate bone loss as well as treatment options that could prevent fragility fractures in this population.

Fracture Liaison Service (FLS) for secondary prevention of fragility fractures: the Italian IMPACT Project

Osteoporosis and subsequent fragility fractures are an important public health issue since this is a common disease that leads to disability, and increased mortality, and therefore has a significant social and economic impact. Several studies have highlighted a dramatic diagnostic-therapeutic gap. A coordinated multidisciplinary system, known as the fracture liaison service (FLS) model, is the most appropriate approach for osteoporosis management and secondary prevention. Developed by the International Osteoporosis Foundation (IOF) through its Capture the Fracture campaign, the FLS model aims to avoid fragmentation of the care pathway by facilitating communication and coordination between primary care and medical specialists. The approach also involves patient identification and education, risk evaluation, the approval of treatments, and long-term follow up. The development of FLS programs has been strongly supported by the IOF. In Italy’s case, the primary recommendations made by the IOF in order to improve the management of patients with fragility fractures, and reverse the expected increase in the number of such fractures and their relative cost over the next 10 years, include the development of dedicated multidisciplinary care pathways, based on the FLS model. In order to make an effective contribution to the organizational needs in this regard, the primary objective of the IMPACT Project is to support the implementation and customization, in selected pilot centers in Italy, of an FLS model in line with the IOF recommendations and coherent with the Italian National Health Service (SNN), and to identify connection points with the territory, the activities of new healthcare professionals, and digital touchpoints in the care pathway.

Sex Difference in the Association of Osteoporosis and Osteopenia Prevalence in Patients with Adrenal Adenoma and Different Degrees of Cortisol Excess.

Objective Osteoporosis and osteopenia (OS/OP) are frequent in patients with adrenal adenomas associated with cortisol excess (CE). However, the relationship between OS/OP and CE severity considering sex differences is unknown. Design A cross-sectional observational study from January 2006 to December 2015. Patients. 237 patients with adrenal adenoma associated with CE, including Cushing's syndrome and mild autonomous cortisol secretion (MACS), diagnosed in 10 referral centers in Japan. MACS was defined by 1 mg overnight dexamethasone suppression test (DST) cortisol level >1.8 μg/dL. Measurements. Prevalence of fragility fractures, medication for osteoporosis, and bone mineral density. Results In total, 112 of 237 patients, who were predominantly female (P < 0.001) and had lower BMI (P=0.013), had OS/OP. Patients with OS/OP was significantly affected by CE (P < 0.01) than those without. The adjusted odds ratio (OR) for predicting OS/OP was obtained in multivariate logistic regression analysis. Clinical measures of CE, 1 mg DST cortisol levels, were positively associated with OS/OP in total cases (OR 1.124, 95% CI: 1.070–1.181, P < 0.001) and the cases with MACS (OR 1.156, 95%CI: 1.046–1.278, P=0.005). A cutoff value of 1 mg DST cortisol level >5.0 μg/dL was associated with OS/OP differently between men and women. OS/OP risk in men with MACS was significantly affected only by 1 mg DST cortisol levels. However, OS/OP risk in women with MACS was significantly affected by 1 mg DST cortisol levels and age. Conclusions CE severity in adrenal adenoma is positively associated with OS/OP. However, the associated factors of OS/OP in the patients with MACS are different between men and women.

Physical Therapist Management of Patients With Suspected or Confirmed Osteoporosis: A Clinical Practice Guideline From the Academy of Geriatric Physical Therapy.

A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development group (GDG) that was appointed by the Academy of Geriatric Physical Therapy (APTA Geriatrics). The GDG consisted of an exercise physiologist and 6 physical therapists with clinical and methodological expertise. The guideline was based on a systematic review of existing clinical practice guidelines, followed by application of the ADAPTE methodological process described by Guidelines International Network for adapting guidelines for cultural and professional utility. The recommendations contained in this guideline are derived from the 2021 Scottish Intercollegiate Guideline Network (SIGN) document: Management of Osteoporosis and the Prevention of Fragility Fractures. These guidelines are intended to assist physical therapists practicing in the United States, and implementation in the context of the US health care system is discussed.

86 Adherence to Best Practice Tariffs (BPT) for Neck of Femur (NOF) Fracture Admissions During the COVID-19 Pandemic

IntroductionFor patients with fragility hip fractures, care needs to be promptly organised to undertake a holistic assessment and preparation for surgery. The aim of the Best Practice Tariffs (BPT) is to promote hip fracture programmes that provide best practice in the care and secondary prevention of fragility fractures.MethodRetrospective audit.Time frame: 11/03/2020 – 22/04/2020.Data retrieved from trauma management and radiology systems.ResultsAmong 33 patients with mean age of 82, 61 % showed compliance to BPT criteria.39% did not meet the criteria: 33% had delayed surgery >36 hours, 3% had delayed orthogeriatric assessment, and 3% not fit for surgery.33 % delayed surgeries due to requirement for medical optimisation, and further investigation.Among COVID patients: 41.6 % mortality rate, of which 40 % were perioperative.There was a loss of BPT income (around £17k) during these unprecedented times. However, the provisions of NOF care did not fluctuate despite extreme pressures on our services.ConclusionsEnsuring all members of the MDT have access to clinical management system.Implementation of early supported discharge programmes allowed reduction in length of acute hospital stay (from 14.2 in Jan 2020 to 8 in March 2020).Improving access to pacemaker check services.

Digital health interventions for osteoporosis and post-fragility fracture care.

The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term ‘Digital Health’ covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.

Vertebral fragility fractures in osteoporosis – A comprehensive review on its management

Introduction: Approximately 20% of individuals older than 50 years of age have been reported to present with vertebral fragility fractures (VFF) – a prevalence which is anticipated to steadily increase in future. VFF is associated with disabling pain, significant impairment of quality of life, reduced ambulatory capacity, impaired social interactions, and poor quality of sleep. Early detection, appropriate management, evaluation of osteoporosis, and prevention of future fragility fractures would form the crux of treatment. Nevertheless, there is no consensus on what constitutes the ideal management protocol for symptomatic VFF. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used to prepare this review. A detailed review of the literature was performed using PubMed, EMBASE, MEDLINE, and Cochrane Database of Systematic Reviews, which were searched for eligible studies with terms “treatment of VEF,” “osteoporotic vertebral fracture (OVF),” “management of osteoporotic compression fracture,” “imaging in OVF,” “percutaneous vertebral augmentation,” and “conservative treatment of OVF” from inception to November 2021. Duplicate studies, case reports, and letters to the editor were excluded from the study. Results: A total of 286 studies were identified using our search criteria. Of these, 142 were duplicates and 107 did not meet inclusion criteria. After removal of these articles through various stages of screening, a total of 37 studies were finally included in the review. Plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) are helpful in the diagnosis, evaluation, and management of these fractures. Radiologically, unstable VFFs need to be identified based on the following criteria (&gt;50% vertebral height loss, kyphosis ≥25–35°, substantial retropulsion of bony fragments, significant bony, or ligamentous posterior column injuries). Conservative treatment (which includes analgesics, orthoses, and early mobilization) has remained the traditional way of treating these fractures. More recent systematic reviews have demonstrated a significant improvement in early pain control, vertebral height restoration, and ambulation with percutaneous augmentation (PKP or PVP) procedures. These studies have recommended cement augmentation in patients with intractable pain, not responding to medications. Surgical stabilization is recommended in elderly patients with pseudoarthrosis, substantial intervertebral instability, intractable pain with vertebral collapse, neurological deficit, and kyphosis. The need for long-term medical therapy to improve the bone density cannot be understated. Conclusion: A high index of suspicion is necessary to diagnose VFFs in elderly patients with back pain. Conservative treatment has remained the traditional way of treating these fractures. Recent evidence shows early pain control and better vertebral height restoration with cement augmentation procedures (PKP or PVP). Open surgical stabilization can be helpful in a subset of patients with substantial intervertebral instability, deformity, and neuro-deficit.

Multidisciplinary Consensus on the Prevention and Treatment of Osteoporosis and Fragility Fractures in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy.

Patients with prostate cancer (PCa) on androgen-deprivation therapy (ADT) are at high risk of osteoporosis and fragility fractures. We aimed to provide some practical insights into the delivery of optimal bone health care for PCa patients, particularly those on ADT. An interdisciplinary group of experts, including urologists and rheumatologists developed recommendations based on their expertise, current evidence and guidelines. The multidisciplinary group's main recommendations are: fragility fracture risk should be assessed in all PCa patient, especially, in those under ADT. FRAX® tool may be incorporated into clinical practice to identify patients at high risk of fracture. Bone mineral density (BMD) should be measured routinely by dual energy X-ray absorptiometry in all patients scheduled for or on ADT. Thoracic and lumbar spine X-ray may be performed at the initial evaluation of patients with the diagnosis of osteoporosis and in case of suspected clinical vertebral fracture. Basic laboratory tests are recommended to exclude secondary osteoporosis. Treatment with bisphosphonates or denosumab should be considered in patients on ADT with fragility fracture, osteoporosis (BMD T-score ≤−2.5), or high risk of fracture according to FRAX®. Referral to a bone metabolism specialist should be contemplated in some cases. The recommendations provided in this document, tailored for clinicians treating PCa patients, may be of help to identify and treat patients at high risk of fracture.

Establishment of a preliminary FRAX®-based intervention threshold for rheumatoid arthritis-associated fragility fracture: a 3-year longitudinal, observational, cohort study.

Background:To establish a FRAX®-based prediction model for rheumatoid arthritis (RA)-associated fragility fracture.Methods:This study is a longitudinal, real-world, registry cohort study. Patients with RA were registered to start in September 2014. The baseline demographics, bone mineral density (BMD), and risk factors of osteoporosis or fragility fracture were recorded. Subsequent fragility fractures during the 3-year observation period were also recorded. We developed a fixed intervention threshold (FITD) to identify fractures by choosing an optimal cut-off point on the receiver operating characteristic (ROC) curve and FRAX®. Several models for intervention thresholds (IT), including fixed intervention threshold (Taiwan) (FITT), age-specific individual intervention threshold (IIT), and hybrid intervention threshold (HIT), were compared to evaluate which IT model will have better discriminative power.Results:As of December 2020, a total of 493 RA participants have completed the 3-year observation study. The mean age of the participants was 59.3 ± 8.7, and 116 (23.5%) new fragility fractures were observed during the study period. In terms of pairwise comparisons of area under the curve (n, 95% confidence interval) in the ROC curve, the FITD (0.669, 0.610–0.727, p < 0.001) with a value of 22% in major osteoporotic fracture and FITT (0.640, 0.582–0.699, p < 0.001) is significantly better than reference, but not for IIT (0.543, 0.485–0.601, p = 0.165) and HIT (0.543, 0.485–0.601, p = 0.165).Conclusion:An optimal FIT is established for intervention decisions in RA-associated fragility fractures. This model can offer an easy and simple guide to aid RA caregivers to provide interventions to prevent fragility fractures in patients with RA.

Bone-Active Medication Utilization from 2013-2017 Amid Beneficiaries Aged 65+ with Medicare Part D by Provider Type

As the United States’ population increasingly consists of older adults aged 65+, an increase is expected in the prevalence of osteoporosis and the number of osteoporotic fractures. Bone-active medications (BAM) delay osteoporosis progression and prevent fragility fractures, but historically low treatment persistence rates and drug utilization for BAM exist among at-risk older adults. This research assessed for differences in the BAM utilization rates over five-years in Medicare Part D by provider type: geriatric specialists (GERO), generalists, specialists, nurse practitioners (NP), and physicians’ assistants (PA). This longitudinal retrospective analysis included providers with at least one BAM prescription among beneficiaries aged 65+. An analysis of response profiles was used to model the mean BAM utilization rates overall and by provider group. Of the 50,249 providers included in this analysis, 88.15% were generalists, 5.76% specialists, 1.48% GERO, 2.73% NP, and 1.87% PA. From 2013-2017, the prevalence of BAM utilization was 6%. Over the five years, BAM utilization rates did not change significantly, but provider-specific rates were significantly different (F=12.53, p<.001). Provider-specific utilization rates were inconsistent with the highest utilization rates and most considerable variation observed among specialists (14.95%). PAs and NPs’ BAM utilization rates were stable at around 9.02% and 9.20%, but GERO and generalists exhibited the lowest utilization rates, 4.86% and 5.79%, respectively. While specialists had the higher-than-expected utilization rates, the overall and provider-specific BAM utilization rates were low and did not increase over time. Further research is needed to identify how provider-related factors, like geographic region and clinical training, influence underutilization.

Preclinical models of medication-related osteonecrosis of the jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.

Evaluation of risk factors associated with fragility fractures and recommendations to optimise bone health in children with long-term neurological condition.

The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically. Therefore, we aimed to evaluate the risk factors associated with fragility fractures in children with LTNC. In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC on follow-up in the paediatric neurology clinic and patients who presented with fracture to the paediatric orthopaedic clinic. Information on patients' demographics, medical history, intervention, biochemical bone markers and fracture history was collected. In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (Gross Motor Function Classification System [GMFCS] V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or were on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% and 33% of the patients had undergone measurements of vitamin D and calcium levels, respectively. The local prevalence of fragility fractures in children with LTNC on follow-up at the neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimise bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight children, avoiding vitamin D deficiency and ensuring adequate calcium intake.

Economic Impact of Osteoporosis Related Hip Fractures in Bahrain. A Systematic Review

Background:Fragility fractures are common due to osteoporosis and there is very limited data on hip fractures from the Middle East in general and Kingdom of Bahrain in particular. The aim of this paper is to review the published data of femoral fractures in the Middle East and extrapolate the financial burden of osteoporosis related hip fractures in Bahrain and suggest some course of action for the region in controlling the fragility fractures.Methods:An extensive search was performed on published studies on hip fracture from 1990 to 2020 by a Medline, EMBASE the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and the Science Citation Index, Bahrain Medical Bulletin, Qatar Medical J, Oman with the key words: Osteoporosis, osteopenia, fragility hip fractures. The inclusion criterion was studies published during 1990-2020 describing the prevalence of osteoporosis and proximal hip fractures in patients with ≥50 years, from the Kingdom of Bahrain, Saudi Arabia, State of Kuwait, Sultanate of Oman, United Arab Emirates, State of Kuwait, Iraq, Iran, Turkey and the State Hashemite Kingdom of Jordan. Based on the fractures per 1000, an average was taken and extrapolated for the Kingdom of Bahrain and direct and indirect costs were assessed.Results:A total of 19 studies were selected for analysis from 10 countries. The average prevalence of postmenopausal osteoporosis was 29.37±6.97% (Range 20.2 to 38.5). In these 10 countries, 252.411 million people live, with an average of 28.56% suffering from osteoporosis. A total of 72.088 million are at risk of having a fragility fracture. The prevalence of fragility fractures of the proximal femur in six countries means prevalence is 4.41/1000. With this average, it is extrapolated that femoral fractures due to osteoporosis costs Bahrain yearly a total of BD 5.31 million.Conclusion:The prevalence of Osteoporosis is going to increase in Bahrain as the population is aging. This will further increase the economic impact of taking care of elderly patients with osteoporosis and related fractures. Early intervention to diagnose and treat this aging population will reduce the cost and save lives.

Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety.

Patients with CKD are at increased risk of fragility fractures and associated consequences. We discuss the complexity of fracture prevention in CKD, summarize the efficacy and safety of denosumab, and provide an approach to denosumab-induced hypocalcemia. Using predefined terms, we searched PubMed, MEDLINE, and Google Scholar for studies on fracture prevention in CKD and the efficacy and safety of denosumab. We included observational studies, randomized controlled trials (RCTs), meta-analyses, evidence-based reviews, and clinical practice guidelines. The diagnosis of osteoporosis and prevention of related fragility fractures is complex in CKD, particularly in those with advanced and end-staged kidney disease (ESKD). Prior to initiating denosumab, it is important to assess for and optimize CKD-mineral and bone disorders (CKD-MBD). In observational studies and small RCTs, denosumab has been shown to improve bone mineral density and reduce bone turnover in CKD, but there have been no studies focused upon its fracture efficacy. Denosumab-induced hypocalcemia has also been reported, which disproportionately impacts those with ESKD. Risk factors for hypocalcemia with denosumab use in CKD include lower baseline serum calcium and 25 hydroxyvitamin D and both low and high bone turnover. Choosing the "right patient" for denosumab, supplementing with calcium and vitamin D, adjusting calcium dialysate, and close clinical monitoring are essential if considering this drug. With optimization of CKD-MBD, calcium and vitamin D supplementation, and close monitoring, denosumab can be considered in CKD. There are however opportunities to better understand its fracture efficacy and safety in an RCT setting.