Predictors of mortality one year after pelvic fractures in an older population: a retrospective cohort study.

The goal was to investigate if patient characteristics can be used to predict 1-year post-fracture mortality after pelvic fracture. Multivariate logistic regression identified male gender, comorbidities and presence of in-hospital complications as predictors of 1-year mortality. PURPOSE: Osteoporotic pelvic fractures have significant mortality and morbidity in the older population. The aim of this study was to investigate the factors predicting one-year mortality of patients sustaining a low-impact pelvic fracture (pelvic ring and acetabulum). METHODS: A total of 282 patients aged ≥ 65 years presenting with a low-energy pelvic ring (n =254) or acetabular (n =28) fracture to the emergency department at the University Hospitals Leuven were included. Demographic and clinical data were retrospectively collected and predictors for mortality one year after pelvic ring fractures were evaluated. RESULTS: The one-year mortality after osteoporotic pelvic ring fractures and acetabular fractures was respectively 20.4% (95% CI 15.7-26.0) and 14% (95% CI 4.0-32.7). Multivariate logistic regression adjusted for confounders identified male gender (OR 3.18; 95% CI (1.06-9.49), p =0.038), a higher number of comorbidities (OR 1.5; 95% CI (1.16-1.95), p =0.002) and in-hospital complications (OR 5.00; 95% CI (1.39-17.97), p =0.014) as independent predictors of one-year mortality after pelvic ring fractures. CONCLUSION: The one-year mortality after low-energy pelvic is high and can be predicted by different patient characteristics. These findings can guide pelvis fracture treatment decisions in the older population.

Development and validation of an eight-item calcium screener to assess daily calcium intake of patients with osteoporosis in clinical practice.

OBJECTIVE: To validate a short food frequency questionnaire (screener) estimating daily average calcium intake from dietary sources to guide calcium supplementation of patients with osteoporosis in clinical practice. METHODS: An eight-item calcium screener was developed based on existing literature, food consumption data and expert opinion. Convergent validity was determined by comparison with 3-day food records using mean difference, Spearman's correlation coefficients (SCC) and Bland-Altman analysis. Test-retest reliability was assessed by SCC and intraclass correlation coefficients (ICC). We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to identify patients requiring calcium supplementation (<1200 mg dietary calcium intake/day). RESULTS: Fifty-two patients filled out the eight-item calcium screener and the 3-day Food record (mean age of 66.8 ± 12.9 (SD)) and 38 patients filled out the screener twice for reliability analysis (mean age of 65.8 ± 12.8 (SD)). Dietary calcium intake between the calcium screener and food records showed a strong correlation (N = 52 patients, SCC = 0.53, p ≤ 0.001) and mean difference of 21 mg (p = 0.70). Bland-Altman analysis showed agreement within 95% confidence intervals for 49/52 comparisons (94%). Test-retest reliability of the calcium screener was excellent (SCC = 0.96, p ≤ 0.001; ICC = 0.99, p ≤ 0.001). CONCLUSION: The calcium screener shows good convergent validity, reliability and feasibility to estimate daily calcium intake of patients with osteoporosis in routine clinical practice.

Skeletal response to teriparatide in real-life setting: effects of age, baseline bone density and prior denosumab use.

OBJECTIVES: Teriparatide (TPD) is an osteoanabolic agent used in patients with high osteoporotic fracture risk. Predictors of therapeutic response to TPD in real-life setting are not well characterised. This study investigated the influence of previous antiresorptive therapy, age and other patient characteristics on the skeletal response to TPD. METHODS: Retrospective study at the metabolic bone clinic, University Hospitals Leuven, Belgium. Patients with osteoporosis and a high fracture burden received TPD for 9-18 months. Bone mineral density (BMD) was measured at baseline, 9 and 18 months at lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS: BMD at LS increased at 9 months (change mean (standard error) 6.8 % (0.7) p < 0.001) and at 18 months (8.0 % (0.9) p < 0.001), while BMD at FN and TH did not change significantly. Non-response in BMD change at the LS was seen with prior denosumab use (odds ratio 0.21, 95% confidence interval (CI) 0.049-0.912, p = 0.037). Changes in BMD at TH were significantly greater in younger patients and in patients with a lower baseline BMD. CONCLUSION: TPD-induced changes in BMD at TH might depend on age and baseline BMD and at LS on prior denosumab use. The results suggest that these factors may be relevant for clinical decision making when initiating TPD treatment, although larger studies are needed to confirm these findings.

Sarcopenia, osteoporosis and frailty.

Muscles and bones are intricately connected tissues displaying marked co-variation during development, growth, aging, and in many diseases. While the diagnosis and treatment of osteoporosis are well established in clinical practice, sarcopenia has only been classified internationally as a disease in 2016. Both conditions are associated with an increased risk of adverse health outcomes such as fractures, dysmobility and mortality. Rather than focusing on one dimension of bone or muscle mass or weakness, the concept of musculoskeletal frailty captures the overall loss of physiological reserves in the locomotor system with age. The term osteosarcopenia in particular refers to the double jeopardy of osteoporosis and sarcopenia. Muscle-bone interactions at the biomechanical, cellular, paracrine, endocrine, neuronal or nutritional level may contribute to the pathophysiology of osteosarcopenia. The paradigm wherein muscle force controls bone strength is increasingly facing competition from a model centering on the exchange of myokines, osteokines and adipokines. The most promising results have been obtained in preclinical models where common drug targets have been identified to treat these conditions simultaneously. In this narrative review, we critically summarize the current understanding of the definitions, epidemiology, pathophysiology, and treatment of osteosarcopenia as part of an integrative approach to musculoskeletal frailty.

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

Rebound-associated vertebral fractures after denosumab discontinuation in a lung cancer patient with bone metastases.

Denosumab is a commonly used antiresorptive treatment in patients with osteoporosis or solid tumours with bone metastases. Upon denosumab discontinuation, a rebound phenomenon can occur that results in an increased (vertebral) fracture risk. This phenomenon is well-known in the setting of osteoporosis but rarely reported in cancer patients with bone metastases discontinuing denosumab. We present the case of a 43-year old women with lung cancer and bone metastases who suffered multiple vertebral fractures after discontinuation of denosumab.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.

Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019. DATA SOURCES: We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale. STUDY SELECTION: Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8). DATA EXTRACTION: We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality. DATA SYNTHESIS: Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days. CONCLUSIONS: Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty.

Monitors to improve indoor air carbon dioxide concentrations in the hospital: A randomized crossover trial.

BACKGROUND: Ventilation has emerged as an important strategy to reduce indoor aerosol transmission of coronavirus disease 2019. Indoor air carbon dioxide (CO2) concentrations are a surrogate measure of respiratory pathogen transmission risk. OBJECTIVES: To determine whether CO2 monitors are necessary and effective to improve ventilation in hospitals. METHODS: A randomized, placebo (sham)-controlled, crossover, open label trial. Between February and May 2021, we placed CO2 monitors in twelve double-bed patient rooms across two geriatric wards. Staff were instructed to open windows, increase the air exchange rate and reduce room crowding to maintain indoor air CO2 concentrations ≤800 parts per million (ppm). RESULTS: CO2 levels increased during morning care and especially in rooms housing couples (rooming-in). The median (interquartile range, IQR) time/day with CO2 concentration > 800 ppm (primary outcome) was 110 min (IQR 47-207) at baseline, 82 min (IQR 12-226.5) during sham periods, 78 min (IQR 20-154) during intervention periods and 140 min (IQR 19.5-612.5) post-intervention. The intervention period only differed significantly from the post-intervention period (P = 0.02), mainly due to an imbalance in rooming-in. Significant but small differences were observed in secondary outcomes of time/day with CO2 concentrations > 1000 ppm and daily peak CO2 concentrations during the intervention vs. baseline and vs. the post-intervention period, but not vs. sham. Staff reported cold discomfort for patients as the main barrier towards increasing ventilation. DISCUSSION: Indoor air CO2 concentrations in hospital rooms commonly peaked above recommended levels, especially during morning care and rooming-in. There are many possible barriers towards implementing CO2 monitors to improve ventilation in a real-world hospital setting. A paradigm shift in hospital infection control towards adequate ventilation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04770597.

Effects of Orthogeriatric Care Models on Outcomes of Hip Fracture Patients: A Systematic Review and Meta-Analysis.

Orthogeriatrics is increasingly recommended in the care of hip fracture patients, although evidence for this model is conflicting or at least limited. Furthermore, there is no conclusive evidence on which model [geriatric medicine consultant service (GCS), geriatric medical ward with orthopedic surgeon consultant service (GW), integrated care model (ICM)] is superior. The review summarizes the effect of orthogeriatric care for hip fracture patients on length of stay (LOS), time to surgery (TTS), in-hospital mortality, 1-year mortality, 30-day readmission rate, functional outcome, complication rate, and cost. Two independent reviewers retrieved randomized controlled trials, controlled observational studies, and pre/post analyses. Random-effects meta-analysis was performed. Thirty-seven studies were included, totaling 37.294 patients. Orthogeriatric care significantly reduced LOS [mean difference (MD) - 1.55 days, 95% confidence interval (CI) (- 2.53; - 0.57)], but heterogeneity warrants caution in interpreting this finding. Orthogeriatrics also resulted in a 28% lower risk of in-hospital mortality [95%CI (0.56; 0.92)], a 14% lower risk of 1-year mortality [95%CI (0.76; 0.97)], and a 19% lower risk of delirium [95%CI (0.71; 0.92)]. No significant effect was observed on TTS and 30-day readmission rate. No consistent effect was found on functional outcome. Numerically lower numbers of complications were observed in orthogeriatric care, yet some complications occurred more frequently in GW and ICM. Limited data suggest orthogeriatrics is cost-effective. There is moderate quality evidence that orthogeriatrics reduces LOS, in-hospital mortality, 1-year mortality, and delirium of hip fracture patients and may reduce complications and cost, while the effect on functional outcome is inconsistent. There is currently insufficient evidence to recommend one or the other type of orthogeriatric care model.

Independent External Validation of FRAX and Garvan Fracture Risk Calculators: A Sub-Study of the FRISBEE Cohort.

Probabilistic models including clinical risk factors with or without bone mineral density (BMD) have been developed to estimate the 5- or 10-year absolute fracture risk. We investigated the performance of the FRAX and Garvan tools in a well-characterized population-based cohort of 3560 postmenopausal, volunteer women, aged 60 to 85 years at baseline, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort, during 5 years of follow-up. Baseline data were used to calculate the estimated 10-year risk of hip and major osteoporotic fractures (MOFs) for each participant using FRAX (Belgium). We computed the 5-year risk according to the Garvan model with BMD. For calibration, the predicted risk of fracture was compared with fracture incidence across a large range of estimated fracture risks. The accuracy of the calculators to predict fractures was assessed using the area under the receiver operating characteristic curves (AUC). The FRAX tool was well calibrated for hip fractures (slope 1.09, p < 0.001; intercept -0.001, p = 0.46), but it consistently underestimated the incidence of major osteoporotic fractures (MOFs) (slope 2.12, p < 0.001; intercept -0.02, p = 0.06). The Garvan tool was well calibrated for "any Garvan" fractures (slope 1.05, p < 0.001; intercept 0.01, p = 0.37) but largely overestimated the observed hip fracture rate (slope 0.32, p < 0.001; intercept 0.006, p = 0.05). The predictive value for hip fractures was better for FRAX (AUC: 0.841, 95% confidence interval [CI] 0.795-0.887) than for Garvan (AUC: 0.769, 95% CI 0.702-0.836, p = 0.01). The Garvan AUC for "any Garvan" fractures was 0.721 (95% CI 0.693-0.749) and FRAX AUC for MOFs was 0.708 (95% CI 0.675-0.741). In conclusion, in our Belgian cohort, FRAX estimated quite well hip fractures but underestimated MOFs, while Garvan overestimated hip fracture risk but showed a good estimation of "any Garvan" fractures. Both models had a good discriminatory value for hip fractures but only a moderate discriminatory ability for MOFs or "any Garvan" fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Epidemiology and secular trends of pelvic fractures in Belgium: A retrospective, population-based, nationwide observational study.

INTRODUCTION: Fractures of the pelvis and acetabulum are associated with osteoporosis, and their incidence is rising in older adults. In the last decade an increasing number of these fractures are being operated in older patients in certain regions. The goal of this study was to describe the incidence of pelvic and acetabular fractures in Belgium between 1988 and 2018. MATERIALS & METHODS: This retrospective, nationwide, population-based study was conducted with the help of the national health insurance database from the Belgian National Institute for Health and Disability Insurance (NIHDI-RIZIV-INAMI). Multiple codes for the reimbursement of the diagnosis and treatment of pelvic and acetabular fractures were collated and (since 2006) linked to the patients' age group, sex and region. RESULTS: Between 1988 and 2018, 91.317 pelvic and acetabular fractures were diagnosed. The overall incidence increased from 15,8/100.000 persons per year in 1988 to 29,7/100.000 persons per year in 2006 and to 37,6/100.000 persons per year in 2018. These fractures showed a bimodal incidence, with a small peak in children (particularly boys), and an increasing incidence in older adults, particularly in women. Between 2006 and 2018, 5.957 (12,4%) patients underwent surgical treatment for their pelvic fracture. 2.088 patients underwent an osteosynthesis of the acetabulum and 3869 patients underwent an osteosynthesis of the pelvic ring. There were 3622 osteosynthesises (60.8%) in patients younger than 60 years old and 2335 (39,1%) in patients over 60 years old. CONCLUSION: There is an increasing incidence of pelvic and acetabular fractures in Belgium with the majority of these fractures occurring in older people. Younger adults have the highest proportion of surgical treatment, but given the much higher incidence in older adults, there is a considerable amount of operations in older adults too.

Corrigendum: Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

[This corrects the article DOI: 10.3389/fendo.2021.641543.].

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Frailty and Mortality in Hospitalized Older Adults With COVID-19: Retrospective Observational Study.

OBJECTIVES: To determine the association between frailty and short-term mortality in older adults hospitalized for coronavirus disease 2019 (COVID-19). DESIGN: Retrospective single-center observational study. SETTING AND PARTICIPANTS: Eighty-one patients with COVID-19 confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), at the Geriatrics department of a general hospital in Belgium. MEASUREMENTS: Frailty was graded according to the Rockwood Clinical Frailty Scale (CFS). Demographic, biochemical, and radiologic variables, comorbidities, symptoms, and treatment were extracted from electronic medical records. RESULTS: Participants (N = 48 women, 59%) had a median age of 85 years (range 65-97 years) and a median CFS score of 7 (range 2-9); 42 (52%) were long-term care residents. Within 6 weeks, 18 patients died. Mortality was significantly but weakly associated with age (Spearman r = 0.241, P = .03) and CFS score (r = 0.282, P = .011), baseline lactate dehydrogenase (LDH; r = 0.301, P = .009), lymphocyte count (r = -0.262, P = .02), and RT-PCR cycle threshold (Ct, r = -0.285, P = .015). Mortality was not associated with long-term care residence, dementia, delirium, or polypharmacy. In multivariable logistic regression analyses, CFS, LDH, and RT-PCR Ct (but not age) remained independently associated with mortality. Both age and frailty had poor specificity to predict survival. A multivariable model combining age, CFS, LDH, and viral load significantly predicted survival. CONCLUSIONS AND IMPLICATIONS: Although their prognosis is worse, even the oldest and most severely frail patients may benefit from hospitalization for COVID-19, if sufficient resources are available.