High Risk Of Fragility Fractures Research Articles

Abstract 98

Background: There is an increased risk of fragility fractures in patients with type 2 diabetes mellitus (T2DM). Bone mineral density (BMD) as measured by DEXAmay be increased despite poor quality of bone and thus FRAX may underestimate the risk of fractures in this population. HR-pQCT is a non-invasive imaging modality for assessment of volumetric BMD (vBMD) and microarchitecture of cancellous and cortical bones. Also the available data regarding the choice of anti-osteoporotic therapy in T2DM are based on either preclinical studies or posthoc/subgroup analysis of randomized controlled trials (RCTs) with no head-to-head comparison. We aim to compare the efficacy of the three most commonly used anti-osteoporotic medications, namely, teriparatide, zoledronate and denosumab, in a cohort of postmenopausal women with T2DM at a high risk of incident fragility fractures. Methods: Here we present the interim analysis after 6 months of an open-labelled randomised control trial of 120 postmenopausal women with T2DM enrolled for 18 months follow-up. Patients were randomised into 4 groups in 1:1:1:1 ratio, with group Areceiving teriparatide, group B receiving zoledronate, Group C receiving denosumab each along with calcium and vitamin D supplements and group D receiving only calcium and vitamin D supplements. The objective was to determine the effects of the anti-osteoporotic drugs on HR-pQCT parameters at the end of 6 months compared to at the time of enrolment. Results: 31 patients who completed their 6 months follow-up were included in the analysis, 8 in group A, 7 in group B and D and 9 in group C. There were no significant change in the vBMD amongst the groups at 6 months at both tibia (p = 0.075) and radius (p = 0.067). There was a decrease in the total vBMD in all the 4 groups at tibia. However at the radius, total vBMD increased in group B and decreased in the rest, however the intra-group changes were not significant. There was a statistically significant difference in trabecular spacing at tibia between group A (increased) and group C (decreased) (p = 0.031). There were no significant changes in other bone microarchitecture parameters. Conclusion: At the end of 6 months, there were no significant changes in volumetric BMD and bone microarchitecture at both tibia and radius amongst the groups except for trabecular spacing. Larger number of patients with longer follow-up would help in further understanding.

An Epidemiological Analysis of Orthopedic Fractures, a Retrospective Single-Center Study from Jordan

Background: Studies on musculoskeletal fractures are limited in Jordan. Therefore, this study includes all orthopedic fractures in the tertiary center from Jordan. Fractures are evaluated for etiologies, age distribution, gender, mechanism of injury, and associated injuries. Therefore, this could assist in discovering the needs of our healthcare system and endorse recommendations on fracture treatment and prevention. Materials and Methods: This retrospective study reviewed 3,387 fractures admitted from July 2018 to December 2021 at King Hussein Medical City in Amman, the capital of Jordan. Fractures were assessed regarding age, gender, mechanism of injury and variation across years. Fractures were allocated into eleven bones where forearm, hand, leg and foot were considered individual bones to facilitate analysis. Results: The males represented 57.8% of patients. The lower limb was affected in 47.4%, the femur was the most commonly affected bone (26.6%), and the proximal femur accounted for 20.9% of all fractures. Men were more likely to sustain injuries to long bone, hand and foot injuries, while women were at higher risk of fragility fractures. Most hospitalizations were in patients over the age of fifty. Two-thirds of injuries were induced by simple falls. Open fractures were reported in 7.3% of fractures and neurological and vascular injuries in 1.9% and 1.5%, respectively. Conclusions: Multicenter and epidemiological studies are needed to adequately assess orthopedic fractures in Jordan so that we can establish guidelines for fracture prevention and treatment.

Pharmacological, Nutritional, and Rehabilitative Interventions to Improve the Complex Management of Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease: A Narrative Review.

Osteoporosis is a highly prevalent condition affecting a growing number of patients affected by chronic obstructive pulmonary disease (COPD), with crucial implications for risk of fragility fractures, hospitalization, and mortality. Several risk factors have been identified to have a role in osteoporosis development in COPD patients, including corticosteroid therapy, systemic inflammation, smoke, physical activity levels, malnutrition, and sarcopenia. In this scenario, a personalized multitarget intervention focusing on the pathological mechanisms underpinning osteoporosis is mandatory to improve bone health in these frail patients. Specifically, physical exercise, nutritional approach, dietary supplements, and smoke cessation are the cornerstone of the lifestyle approach to osteoporosis in COPD patients, improving not only bone health but also physical performance and balance. On the other hand, pharmacological treatment should be considered for both the prevention and treatment of osteoporosis in patients at higher risk of fragility fractures. Despite these considerations, several barriers still affect the integration of a personalized approach to managing osteoporosis in COPD patients. However, digital innovation solutions and telemedicine might have a role in optimizing sustainable networking between hospital assistance and community settings to improve bone health and reduce sanitary costs of the long-term management of COPD patients with osteoporosis.

Risk of fragility fractures in individuals with diabetes. An observational and Mendelian randomization study

Background and Aims : Smaller observational studies indicate that individuals with diabetes have a high risk of fragility fractures, possibly because of microvascular disease. We aimed 1) to investigate the observational risk of fragility fractures in individuals with diabetes, and 2) to use Mendelian randomization to assess whether glucose levels have a causal effect on fragility fracture risk.

Gaps and alternative surgical and non-surgical approaches in the bone fragility management: an updated review.

Osteoporotic fractures are one of the major problems facing healthcare systems worldwide. Undoubtedly, fragility fractures of the hip represent a far greater burden in terms of morbidity, mortality, and healthcare costs than other fracture sites. However, despite the significant impact on the health and quality of life of older adults, there is a general lack of awareness of osteoporosis, which results in suboptimal care. In fact, most high-risk individuals are never identified and do not receive adequate treatment, leading to further fragility fractures and worsening health status. Furthermore, considering the substantial treatment gap and the proven cost-effectiveness of fracture prevention programs such as Fracture Liaison Services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are adequately assessed and treated. Based on this evidence, the aim of our review was to (i) provide an overview and comparison of the burden and management of fragility fractures, highlighting the main gaps, and (ii) highlight the importance of using alternative approaches, both surgical and non-surgical, with the aim of implementing early prevention of osteoporotic fractures and improving the management of osteoporotic patients at imminent and/or very high risk of fracture.

1071 INCIDENCE OF RECORDED OSTEOPOROSIS, OSTEOPENIA AND FRAGILITY FRACTURE IN OLDER PEOPLE: ANALYSIS OF UK PRIMARY CARE DATA

Abstract Introduction Osteoporosis is common in later life, leading to fragility fractures associated with increased mortality, disability, and costs. There is a surprising lack of data regarding the incidence of osteoporosis. We aimed to estimate the incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in older people, explore time trends in diagnosis, and differences by age, sex, and social deprivation. Method We used de-identified patient data provided as part of routine primary care (IQVIA Medical Research Database (IMRD). All patients aged 50-99y registered with THIN (The Health Improvement Network) participating practices between 1/1/2000–31/12/2018 were included. Crude incidence rates (IR) were estimated per 10,000 person-years (PY). We used Poisson regression to calculate adjusted Incidence Rate Ratios (IRR) accounting for sex, age, calendar year and deprivation. Results The IR of osteoporosis was significantly higher in women, 84.32 (95%CI 83.81–84.83) vs. 16.66 (95%CI 16.43–16.90) in men per 10,000PY. In women, recorded IR of osteoporosis reached a peak in 2009. In the adjusted model, older men in most deprived areas had a higher IRR of osteoporosis [1.67 (95% 1.59–1.74)] compared to those in least deprived areas. Women were more likely to be diagnosed with osteopenia compared to men, at any age. Incidence of osteopenia diagnosis increased over time. In the adjusted model, men in most deprived areas had a higher IRR of osteopenia [1.44 (95%CI 1.35–1.53)] compared to least deprived areas. The IR of fragility fracture was higher in women, 84.97 (95%CI 84.45–85.48) vs. 31.15 (95%CI 30.83–31.48) in men per 10,000PY. In the adjusted model, men in most deprived areas had an increased IRR of fragility fracture [1.53 (95%CI 1.48–1.59)] compared to least deprived areas. Conclusion Community bone health interventions might be targeted at populations at higher risk of fragility fractures, including older men living in socially deprived areas.

Bone Health in Children with Rheumatic Disorders: Focus on Molecular Mechanisms, Diagnosis, and Management.

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism.

Bridging the Gap: Bone Health Education for Specialists

Our recent scoping review of the perceptions about the importance of treating fractures and osteoporosis among key stakeholders showed the literature on the perceptions of specialist physicians is very limited. Existing literature suggests that recognition of fragility fractures as a sign of underlying bone disease is still low, even among physicians. To increase awareness of osteoporosis as the underlying cause of fragility fracture among specialist physicians who treat patients at high risk of fragility fracture. We have produced a series of educational modules directed at the specialists who would typically treat patients with an increased risk of osteoporosis and fragility fracture due to glucocorticoid use, a plethora of medical conditions or immobility. N/A We are looking to present these materials across the Asia Pacific region in 2022 and beyond. The modules will be available free of charge through the Asia Pacific Fragility Fracture Alliance website ( https://apfracturealliance.org ) and we encourage leaders of all specialties to help raise awareness and increase the rates of osteoporosis identification, diagnosis and management in at-risk populations.

Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.

Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.

Sarcopenic Dysphagia, Malnutrition, and Oral Frailty in Elderly: A Comprehensive Review

Frailty is a highly prevalent condition in the elderly that has been increasingly considered as a crucial public health issue, due to the strict correlation with a higher risk of fragility fractures, hospitalization, and mortality. Among the age-related diseases, sarcopenia and dysphagia are two common pathological conditions in frail older people and could coexist leading to dehydration and malnutrition in these subjects. “Sarcopenic dysphagia” is a complex condition characterized by deglutition impairment due to the loss of mass and strength of swallowing muscles and might be also related to poor oral health status. Moreover, the aging process is strictly related to poor oral health status due to direct impairment of the immune system and wound healing and physical and cognitive impairment might indirectly influence older people’s ability to carry out adequate oral hygiene. Therefore, poor oral health might affect nutrient intake, leading to malnutrition and, consequently, to frailty. In this scenario, sarcopenia, dysphagia, and oral health are closely linked sharing common pathophysiological pathways, disabling sequelae, and frailty. Thus, the aim of the present comprehensive review is to describe the correlation among sarcopenic dysphagia, malnutrition, and oral frailty, characterizing their phenotypically overlapping features, to propose a comprehensive and effective management of elderly frail subjects.

Bony deformities in a child with untreated osteogenesis imperfecta type III

Osteogenesis Imperfecta (OI) is a skeletal dysplasia that affects the cross-linking of Type 1 collagen leading to a wide spectrum of manifestations including bony abnormalities, scleral abnormalities, dentinogenesis imperfecta, and hearing abnormalities [1]. Orthopedic manifestations of OI include basilar invagination, kyphoscoliosis, codfish vertebrae, bowing deformities of the long bones, coxa vara, protrusion acetabuli, pathologic fractures, and radial head dislocations [1]. The Sillence Classification, originally designed to describe Types I – IV, has been expanded upon to includes Type V, VI, VII, which do not have a Type I collagen mutation, and instead have other genetic explanations (CRTAP, LEPRE1 genes) for the abnormal bone seen on microscopy [1,2]. Type I, IV represent milder forms of disease, Type V-VII represent milder forms of disease, Type III is the most severe survivable form, and Type II is lethal at birth [1,2]. We present a case of Sillence Type III OI, diagnosed by genetic analysis at birth, with significant bony deformities. She did not have appropriate multidisciplinary medical management of her condition and presented to our clinic at age 14. Radiographs of the spine and extremities demonstrated kyphoscoliosis, bilateral protrusio acetabuli, multiapical bowing bony deformities of femora, tibia, humeri, forearm, radial head dislocations, and short stature. This case highlights the importance of multidisciplinary management for children with OI. This includes physical rehabilitation [3], bisphosphonates [3,4] and more recently gene therapies [3,4], and stem cell transplantation therapies [4]. Patients with Osteogenesis Imperfecta Type III have a limited lifespan [5] and it is important to maximize the advantage of medical therapies. In the absence of the appropriate medical care, osteogenesis imperfecta can develop progressive deformities in the long bones, a high risk of fragility fractures, and progressive kyphoscoliosis that can be difficult to manage surgically due to underlying osteopenia.

Associations of variability in body weight and glucose levels with the risk of hip fracture in people with diabetes

BackgroundDiabetes is associated with a high risk of fragility fracture. However, there are controversies regarding the effect of fluctuations in metabolic parameters on the risk of fracture. We aimed to investigate the associations of body weight or glucose variability or their combination with the risk of hip fracture in people with diabetes. MethodsA population-based cohort study with 480,539 subjects over 40 years who had undergone three or more health examinations was performed. The degree of variability was evaluated using variability independent of the mean (VIM, 100 × standard deviation / meanbeta), coefficient of variation (CV), and average real variability (ARV, average of the absolute differences between consecutive values). High variability was defined as having values in the highest quartile. Cox proportional hazards models were used to estimate the risk of hip fracture. ResultsThere were 2834 hip fracture events (0.59%) during the mean follow-up of 8.1 years. After multivariable adjustment for age, sex, alcohol consumption, smoking, regular exercise, income, glucose, body mass index, hemoglobin, estimated glomerular filtration rate, diabetes duration, diabetes treatment with multiple agents, and osteoporosis, the HRs (95% CI) of hip fracture were 1.36 (1.24–1.50) and 1.29 (1.16–1.43) for high body weight VIM and high glucose VIM, respectively. The HR (95% CI) of both high VIM group was 1.63 (1.44–1.83), suggesting an additive effect of variabilities in body weight and glucose. The results were consistent when using CV and ARV and in various sensitivity analyses. ConclusionsHigh variability in body weight and glucose levels is associated with an increased incidence rate and risk of hip fracture in people with diabetes.

The association of cardio-metabolic risk factors and history of falling in men with osteosarcopenia: a cross-sectional analysis of Bushehr Elderly Health (BEH) program

BackgroundOsteosarcopenia, defined as sarcopenia plus osteopenia/osteoporosis, may increase the risk of fractures and affects morbidity and mortality in the older population. Falling is also common in the elderly and increases the risk of fractures and mortality. We examined the association of cardio-metabolic risk factors with a history of falling in osteosarcopenic men.MethodsWe used the baseline data of the Bushehr Elderly Health (BEH) program. Osteosarcopenia was defined as having both sarcopenia (reduced skeletal muscle mass plus low physical performance and/or low muscle strength) and osteopenia/osteoporosis (T-score ≤ − 1.0). Falling was defined as a self-reported history of an unintentional down on the ground during the previous year before the study. We used logistic regression analysis to estimate the adjusted odds ratio (AOR) with a 95% Confidence Interval (CI) to quantify the associations.ResultsAll elderly men diagnosed with osteosarcopenia (n = 341), with a mean age of 73.3(±7.4) years, were included. Almost 50(14.7%) participants reported falling. Age showed a positive association with falling (AOR: 1.09, 95%CI: 1.04–1.14). An increase of 10 mmHg in systolic blood pressure(SBP), reduces the odds of falling by 26%(AOR:0.74, 95%CI:0.62–0.89), while a positive association was detected for fasting plasma glucose (FPG), as 10 mg/dl increase in the FPG, raises the chance of falling by 14%(AOR = 1.14, 95%CI:1.06,1.23). Hypertriglyceridemia was inversely associated with falling (AOR = 0.33, 95% CI: 0.12, 0.89).ConclusionsFalling is a major public health problem in rapidly aging countries, especially in individuals with a higher risk of fragility fractures. Older age-raised fasting plasma glucose and low SBP are associated with falling in osteosarcopenic patients. Considering the higher risk of fracture in osteosarcopenic men, comprehensive strategies are needed to prevent fall-related injuries in this high-risk population.

Cortical bone thickness of the distal radius predicts the local bone mineral density.

AimsThe distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD).MethodsA total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability.ResultsThe CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92).ConclusionThe cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening.Cite this article: Bone Joint Res 2021;10(12):820–829.

Osteocyte mechanosensing following short-term and long-term treatment with sclerostin antibody.

Sclerostin antibody romosozumab (EVENITY™, romosozumab-aqqg) has a dual mechanism of action on bone, increasing bone formation and decreasing bone resorption, leading to increases in bone mass and strength, and a decreased risk of fracture, and has been approved for osteoporosis treatment in patients with high risk of fragility fractures. The bone formation aspect of the response to sclerostin antibody treatment has thus far been best described as having two phases: an immediate and robust phase of anabolic bone formation, followed by a long-term response characterized by attenuated bone accrual. We herein test the hypothesis that following the immediate pharmacologic anabolic response, the changes in bone morphology result in altered (lesser) mechanical stimulation of the resident osteocytes, initiating a negative feedback signal quantifiable by a reduced osteocyte signaling response to load. This potential desensitization of the osteocytic network is probed via a novel ex vivo assessment of intracellular calcium (Ca2+) oscillations in osteocytes below the anteromedial surface of murine tibiae subjected to load after short-term (2weeks) or long-term (8weeks) treatment with sclerostin antibody or vehicle control. We found that for both equivalent load levels and equivalent strain levels, osteocyte Ca2+ dynamics are maintained between tibiae from the control mice and the mice that received long-term sclerostin antibody treatment. Furthermore, under matched strain environments, we found that short-term sclerostin antibody treatment results in a reduction of both the number of responsive cells and the speed of their responses, which we attribute largely to the probability that the observed cells in the short-term group are relatively immature osteocytes embedded during initial pharmacologic anabolism. Within this study, we demonstrate that osteocytes embedded following long-term sclerostin antibody treatment exhibit localized Ca2+ signaling akin to those of mature osteocytes from the vehicle group, and thus, systemic attenuation of responses such as circulating P1NP and bone formation rates likely occur as a result of processes downstream of osteocyte Ca2+ signaling.

Factors associated with initiation of bone-health medication among older adults in primary care in Ireland

BackgroundAdults at high risk of fragility fracture should be offered pharmacological treatment when not contraindicated, however, under-treatment is common.ObjectiveThis study aimed to investigate factors associated with bone-health medication initiation in older patients attending primary care.DesignThis was a retrospective cohort study.SettingThe study used data from forty-four general practices in Ireland from 2011–2017.SubjectsThe study included adults aged ≥ 65 years who were naïve to bone-health medication for 12 months.MethodsOverall fracture-risk (based on QFracture) and individual fracture-risk factors were described for patients initiated and not initiated onto medication and compared using generalised linear model regression with the Poisson distribution.ResultsOf 36,799 patients (51% female, mean age 75.4 (SD = 8.4)) included, 8% (n = 2,992) were observed to initiate bone-health medication during the study. One-fifth of all patients (n = 8,193) had osteoporosis or had high fracture-risk but only 21% of them (n = 1,687) initiated on medication. Female sex, older age, state-funded health cover and osteoporosis were associated with initiation. Independently of osteoporosis and co-variates, high 5-year QFracture risk for hip (IRR = 1.33 (95% CI = 1.17–1.50), P < 0.01) and all fractures (IRR = 1.30 (95% CI = 1.17–1.44), P < 0.01) were associated with medication initiation. Previous fracture, rheumatoid arthritis and corticosteroid use were associated with initiation, while liver, kidney, cardiovascular disease, diabetes and oestrogen-only hormone replacement therapy showed an inverse association.ConclusionsBone-health medication initiation is targeted at patients at higher fracture-risk but much potential under-treatment remains, particularly in those >80 years and with co-morbidities. This may reflect clinical uncertainty in older multimorbid patients, and further research should explore decision-making in preventive bone medication prescribing.

Osteoporosis guidelines from a rehabilitation perspective: systematic analysis and quality appraisal using AGREE II.

People affected by osteoporosis and fragility fractures often report disability and poor health-related quality of life. Albeit rehabilitation has a crucial role in older people, post-menopausal women and other subjects with high risk of fragility fractures, the rehabilitation perspective has been poorly investigated in the available guidelines for osteoporosis. The aim of this systematic review was to systematically evaluate the quality of guidelines for osteoporosis from a rehabilitation perspective. On May 2020, we performed a systematic search on medical literature of all guidelines published in the last 10 years on PubMed, Pedro, and international guideline databases. The study selection was based on key terms "exercise," "physical activity" or "rehabilitation." All authors independently assessed the methodological quality through the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, consisting of six domains (scope, stakeholder involvement, rigor and development, clarity of presentation, applicability, editorial independence). Out of 331 documents retrieved, a total of 34 guidelines were selected after the screening phases. Twenty (58.8%) high quality guidelines were reported. According to AGREE II instrument, a mean score of 78.1±21.8% was reported for "scope and purpose" domain; for stakeholder involvement, the mean score was 58.1±22.1%; the rigor of development was good (mean score of 61.3±27.3%); for clarity of presentation the mean score was 79.4±20.3%; the applicability was poor (mean score of 30.9±25.2%); for editorial independence the mean score was 75.1±24.6%. Rehabilitation recommendations for osteoporotic patients were reported in 21 (61.8%) of the selected guidelines. This is the first systematic analysis evaluating quality of the guidelines for osteoporosis using AGREE II instrument. Starting from a state of the art of the currently available evidence, we could conclude that therapeutic exercise at moderate to high intensity is encouraged by several guidelines for the management of people with osteoporosis and fragility fractures. More than half of guidelines were of high-quality. However, most guidelines are lacking specific indications about exercise features. This study might support the implementation of a rehabilitation perspective in the guidelines for osteoporotic patients.

Evaluation of Factors Associated With Fracture and Loss of Bone Mineral Density Within 1 Year After Liver Transplantation

ObjectiveOrthotopic liver transplant recipients are at high risk of fragility fractures both in pre-liver transplant (pre-LT) and in the immediate posttransplant (post-LT) period. The aims of this study were to identify risk factors associated with post-LT fracture and identify factors that contribute to changes in bone mineral density (BMD) in post-LT as they relate to the risk of fracture in the immediate post-LT period. MethodsWe conducted a retrospective cohort study of first-time LT recipients who had BMD testing within 2-year pre-LT and 1-year post-LT. We assessed factors associated with immediate post-LT fracture using logistic regression models and linear regression models. ResultsNew fractures occurred in 41/286 (14.3%) of LT recipients during the first year following LT. In multivariate analysis, we noted an increased odds of fracture for patients with prior history of fracture (P < .001), patients who were older (P = .03), patients with higher end-stage liver disease score (P = .03), and patients with lower BMD. After adjustment for multiple testing, only a history of prior fracture was statistically significant. ConclusionOur study demonstrated that prior fracture at any site was associated with developing a new fracture in the first year post-LT.

Efficacy of Zoledronic Acid in Maintaining Areal and Volumetric Bone Density After Combined Denosumab and Teriparatide Administration: DATA-HD Study Extension.

Combined teriparatide and denosumab rapidly and substantially increases bone mineral density (BMD) at all anatomic sites. Discontinuation of denosumab however, results in high-turnover bone loss and increased fracture risk. The optimal way to prevent this bone loss remains undefined. This study is a preplanned extension of the DATA-HD study, where postmenopausal women with osteoporosis were randomized to receive 9 months of either 20 μg or 40 μg of teriparatide daily overlapping with denosumab (60 mg administered at months 3 and 9). At the completion of this 15-month study, women were invited to enroll in the DATA-HD Extension where they received a single dose of zoledronic acid (5 mg) 24 to 35 weeks after the last denosumab dose. Areal BMD and bone turnover markers were measured at month 27 and 42 (12 and 27 months after zoledronic acid, respectively) and spine and hip volumetric bone density by quantitative CT was measured at month 42. Fifty-three women enrolled in the DATA-HD Extension. At the femoral neck and total hip, the mean 5.6% and 5.1% gains in BMD achieved from month 0 to 15 were maintained both 12 and 27 months after zoledronic acid administration. At the spine, the mean 13.6% gain in BMD achieved from month 0 to 15 was maintained for the first 12 months but modestly decreased thereafter, resulting in a 3.0% reduction (95% CI, -4.0% to -2.0%, p < .0001) 27 months after zoledronic acid. The pattern of BMD changes between months 15 and 42 were qualitatively similar in the 20-μg and 40-μg groups. A single dose of zoledronic acid effectively maintains the large and rapid total hip and femoral neck BMD increases achieved with combination teriparatide/denosumab therapy for at least 27 months following the transition. Spine BMD was also largely, though not fully, maintained during this period. These data suggest that the DATA-HD Extension regimen may be an effective strategy in the long-term management of patients at high risk of fragility fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

High resolution imaging in bone tissue research-review

This review article focuses on imaging of bone tissue to understand skeletal health with regards to bone quality. Skeletal fragility fractures are due to bone diseases such as osteoporosis which result in low bone mass and bone mineral density (BMD) leading to high risk of fragility fractures. Recent advances in imaging and analysis technologies have highly benefitted the field of biological sciences. In particular, their application in skeletal health has been of significant importance in understanding bone mechanical behavior (structure and properties) at the tissue level. While synchrotron based microCT technique has remained the gold standard for non-destructive evaluation of structure in material and biological sciences, several lab based microCT systems have been developed to provide high resolution imaging of specimens with greater access, and ease of use in laboratory settings. Lab based microCT scanners are widely used in the bone field as a standard tool to evaluate three-dimensional (3D) morphologies of bone structure at image resolutions appropriate for bone samples from small animals to bone biopsy specimens from humans. Both synchrotron and standard lab based microCT systems provide high resolution imaging ex vivo for a small sized specimen. A few X-ray based systems are also commercially available for in vivo scanning at relatively low image resolutions. Synchrotron-based CT microscopy is being used for various ultra-high-resolution image analyses using complex 3D software. However, the synchrotron-based CT technology is in high demand, allows only limited numbers of specimens, expensive, requires complex additional instrumentation, and is not easily available to researchers as it requires access to a synchrotron source which is always limited. Therefore, desktop laboratory scanners (microXCT, Zeiss/Xradia, Scanco, SkyScan. etc.), mimicking the synchrotron based CT technology or image resolution, have been developed to solve the accessibility issues. These lab based scanners have helped both material science, and the bone field to investigate bone tissue morphologies at submicron mage resolutions. Considerable progress has been made in both in vivo and ex vivo imaging towards providing high resolution images of bone tissue. Both clinical and research imaging technologies will continue to improve and help understand osteoporosis and other related skeletal issues in order to develop targeted treatments for bone fragility. This review summarizes the high resolution imaging work in bone research.