Search

Patients are increasingly seeking health information on the Internet, but to the best of our knowledge, this has not been previously studied in haematology. We aimed to characterise online health information use and associated variables among adult outpatients in our tertiary-care centre in Flanders, Belgium. During a 6-week period, we distributed 477 anonymous self-administered questionnaires and received 451 (response rate 94.5%), of which 444 (93.1% of total) contained information on Internet use for health information, the primary outcome. Two hundred and thirty-two respondents (52.3%) had ever sought any health information online, and 187 (33.1%) conducted searches pertaining to their haematological disease in the past year. The latter was independently associated with younger age and a higher level of education in multivariate analysis. Internet users ranked the Internet higher and other resources lower as health information resources. Among Internet users, 196 (89.5%) would be interested in a list of reliable websites about their disease. Patients reported positive and negative aspects of online health information-seeking; it increased anxiety in some while it stimulated coping in others. We conclude that haematological patients commonly use the Internet for health information and report both positive and negative aspects of using this medium. [ABSTRACT FROM AUTHOR]

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.

This study aimed to describe the incidence of hospitalizations for osteoporotic fractures in patients aged 50 years and over in Belgium between 2010 and 2021. A declining trend in crude and age-adjusted hospitalization incidence was observed, however, the absolute number of hospitalisations for osteoporotic fractures increased due to demographic changes., Purpose: The secular trends of hospitalizations for hip and other osteoporotic fractures between 2010 and 2021 in patients aged 50 years and over in Belgium are unknown. This study aimed to describe the incidence of hospitalizations for osteoporotic fractures in patients aged 50 years and over in Belgium between 2010 and 2021., Methods: Population-based, retrospective study based on hospitalization data extracted by the national database NIHDI and demographical data retrieved from the Belgian Federal Bureau for Statistics. Data were combined to determine the crude and age-standardized hospitalization incidence of fractures of the hip, distal femur, pelvis, humerus, wrist, and spine (2010 as the reference year)., Results: A total of 445,234 hospitalizations for osteoporotic fractures were reported between 2010 and 2021 (excluding 2015). Hospitalizations increased by 5.8% between 2010 and 2021 (p = 0.013) with a higher increase in men (12.1%; p = 0.001) compared to women (4.1%; p = 0.041). The crude incidence of hospitalizations for all fractures per 100,000 persons per year decreased from 990 to 910 between 2010 and 2021 (p = 0.572). The age-standardized incidence for hospitalizations of any osteoporotic fracture in men declined from 5.30/1,000 to 4.42/1,000 (p = 0.010). In women, a similar decrease was observed (13.84/1,000 to 11.62/1,000; p = 0.003). Both age-standardized hospitalizations for hip and non-hip fractures showed a decrease in both sexes., Conclusion: Although a declining trend in the crude incidence per 100,000 and in the age-adjusted incidence of hospitalizations for osteoporotic fractures was observed, the absolute number of hospitalizations for osteoporotic fractures increased due to the demographic change of an ageing population., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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.

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., Competing Interests: Declaration of competing interest EG has received consultancy and travel fees from Amgen, Alexion, Daiichi Sankyo, Sandoz, Takeda, UCB and Will Pharma. JD and MD have received travel and consultancy fees from Daiichi Sankyo. MRL has received consultancy, travel and lecture fees from Alexion, Amgen, Daiichi Sankyo, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Sandoz, Takeda, UCB, and Will Pharma., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: ML has received consultancy and lecture fees from Alexion, Amgen, Daiichi Sankyo, Kyowa Kirin, Menarini, Orifarm, Sandoz, Takeda, UCB, and Will Pharma. SG has received consultancy, lecture and travel fees from Alexion, Amgen, MSD, Novartis, Takeda, UCB, and Will Pharma. CV has received travel fees from Boehringer Ingelheim. JB has received consultancy, lecture fees and travel support from Alexion, Amgen, Bayer, Sandoz, Takeda, UCB and Will-Pharma. OB has received consultancy fees from Amgen, Biophytis, IBSA, MEDA, Servier, SMB, Teva, TRB Chemedica, and UCB. EC has received consultancy fees from bioMérieux, DiaSorin, Fujirebio, IDS, Menarini, and Nittobo. SR has received travel and consultancy fees from Abbott, Bayer, Eurogenerics, Gedeon Richter, Mylan, Takeda, Theramex, UCB and Will-Pharma. EG has received travel and consultancy fees from Amgen, Alexion, Daiichi Sankyo, Sandoz, Takeda, UCB, and Will Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laurent, Goemaere, Verroken, Bergmann, Body, Bruyère, Cavalier, Rozenberg, Lapauw and Gielen.)

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., (© 2022. Springer Nature Limited.)

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., Competing Interests: JD has received a research grant (11A9320N) and travel support from 10.13039/501100003130Research Foundation Flanders (FWO) as well as a scholarship from Eli Lilly. ML has received conference support and lecture fees from Amgen (related to denosumab), lecture fees from Menarini, and consultancy fees from Alexion, Kyowa Kirin, Sandoz, Takeda and UCB. EG has received lecture fees from Amgen and Takeda, consultancy fees from Alexion and UCB and travel support from 10.13039/100002429Amgen and 10.13039/100011110UCB. WA, MD and IW have no conflicts of interest to declare., (© 2022 The Authors.)

Background: Ventilation has emerged as an important strategy to reduce indoor aerosol transmission of coronavirus disease 2019. Indoor air carbon dioxide (CO 2 ) concentrations are a surrogate measure of respiratory pathogen transmission risk., Objectives: To determine whether CO 2 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 CO 2 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 CO 2 concentrations ≤800 parts per million (ppm)., Results: CO 2 levels increased during morning care and especially in rooms housing couples (rooming-in). The median (interquartile range, IQR) time/day with CO 2 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 CO 2 concentrations > 1000 ppm and daily peak CO 2 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 CO 2 concentrations in hospital rooms commonly peaked above recommended levels, especially during morning care and rooming-in. There are many possible barriers towards implementing CO 2 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., Competing Interests: Declaration of competing interest Dr. Laurent has received consultancy and lecture fees from Alexion, Amgen, Kyowa Kirin, Menarini, Orifarm, Sandoz, Takeda, UCB and Will Pharma, all unrelated to this work. Dr. Frans reports no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: MRL has received consultancy fees from UCB (related to romosozumab), travel support and lecture fees from Amgen, and consultancy fees from Alexion, Kyowa Kirin and Sandoz, unrelated to this work. EG has received consultancy fees from UCB (related to romosozumab) and non-financial support from Amgen unrelated to this work. All other authors have nothing to disclose.

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., (© 2021. The Author(s).)

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., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

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., Competing Interests: ML has received lecture and consultancy fees from Alexion, Amgen, Kyowa Kirin, Menarini, Sandoz, Takeda, UCB and Will-Pharma. JS has received lecture, consultancy fees, and conference support from Kyowa Kirin, Alexion, Eli-Lily, Ferring, Ipsen, Menarini, Novo Nordisk, Pfizer, Sandoz, and Siemens Healthcare. DT has received conference support from Novo Nordisk. NG, JLa, and KH have received consultancy fees from Kyowa Kirin. EB has received conference support from Novo Nordisk and Pfizer. CH has received consultancy fees and conference support from Kyowa Kirin, Novo Nordisk, and Ferring. EC has received consultancy fees from bioMérieux, Diasorin, Fujirebio, IDS, and Menarini. PH is an employee of GlaxoSmithKline but participates in his own capacity. J-FK has received consultancy fees and conference support from Heel Belgium, Sanofi, and TRB Chemedica. KW has received conference support from Alexion, Ferring, Kyowa Kirin and Novo Nordisk. CV has received conference support from Boehringer Ingelheim. GM has received consultancy fees from Alexion, Biomarin, Kyowa Kirin, and Pfizer. EL has received consultancy fees and travel support from Kyowa Kirin, Chiesi, and Recordati. JV has received conference support and consultancy fees from Alexion, Bellco, Ferring, Medtronic, and Kyowa Kirin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laurent, De Schepper, Trouet, Godefroid, Boros, Heinrichs, Bravenboer, Velkeniers, Lammens, Harvengt, Cavalier, Kaux, Lombet, De Waele, Verroken, van Hoeck, Mortier, Levtchenko and Vande Walle.)

This systematic review and meta-analysis found low-quality evidence that orthogeriatric care is positively associated with diagnosis of osteoporosis, prescription of calcium and vitamin D supplements and bisphosphonates in older hip fracture patients. Evidence on fall and fracture prevention was scarce and inconclusive. Orthogeriatrics may reduce the treatment gap following hip fractures., Introduction: Hip fracture patients are at imminent risk of additional fractures and falls. Orthogeriatric care might reduce the osteoporosis treatment gap and improve outcomes in these patients. However, the optimal orthogeriatric care model (geriatric liaison service, co-management, or geriatrician-led care) remains unclear., Purpose: To summarize the association of different orthogeriatric care models for older hip fracture patients, compared to usual orthopaedic care, with fall prevention measures, diagnosis and treatment of osteoporosis and future falls and fractures., Methods: Two independent reviewers retrieved randomized controlled trials (RCTs) or controlled observational studies. Random effects meta-analysis was applied (PROSPERO ID: 165914)., Results: One RCT and twelve controlled observational studies were included, encompassing 20,078 participants (68% women, median ages between 75 and 85 years). Orthogeriatric care was associated with higher odds of diagnosing osteoporosis (odds ratio [OR] 11.36; 95% confidence interval [CI] 7.26-17.77), initiation of calcium and vitamin D supplements (OR 41.44; 95% CI 7.07-242.91) and discharge on anti-osteoporosis medication (OR 7.06; 95% CI 2.87-17.34). However, there was substantial heterogeneity in these findings. Evidence on fall prevention and subsequent fractures was scarce and inconclusive. Almost all studies were at high risk of bias. Evidence was insufficient to compare different care models directly against each other., Conclusions: Low-quality evidence suggests that orthogeriatric care is associated with higher rates of diagnosing osteoporosis, initiation of calcium and vitamin D supplements and anti-osteoporosis medication. Whether orthogeriatric care prevents subsequent falls and fractures in older hip fracture patients remains unclear.

This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover., Design: Prospective cohort study., Methods: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied., Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered., Conclusions: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

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., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hypophosphatasia (HPP) is a rare metabolic bone disorder caused by mutations in the alkaline phosphatase (ALPL) gene, and characterized by low circulating alkaline phosphatase (ALP) levels and bone, muscle, dental and systemic manifestations. In this case series we investigate the clinical spectrum, genetic and biochemical profile of adult HPP patients from the University Hospitals Leuven, Belgium., Methodology: Adults with HPP were identified through medical record review. Inclusion criteria were: (1) age ≥ 16 yr; (2) consecutively low ALP levels not explained by secondary causes; (3) one or more of the following supporting criteria: biochemical evidence of elevated enzyme substrates; subtrochanteric fractures, metatarsal fractures or other typical clinical features; family history of HPP; a known or likely pathogenic ALPL mutation., Results: Nineteen patients met our inclusion criteria (n = 2 infantile, n = 6 childhood, n = 10 adult-onset HPP and one asymptomatic carrier). Fractures and dental abnormalities were the most reported symptoms. Fatigue was reported in n = 7/19 patients (37%), three of which had previously been misdiagnosed as having chronic fatigue syndrome and/or fibromyalgia. Empirical pyridoxine therapy in four patients (without seizures) did not provide symptomatic relief. N = 7/19 patients (37%) were inappropriately treated or planned to be treated with antiresorptive treatment. Two patients developed atypical femoral fractures following exposure to bisphosphonates and/or denosumab. Patients detected by screening were less severely affected, while patients with homozygous or compound heterozygous mutations had the most severe symptoms, significantly lower circulating ALP levels (p = 0.013) and significantly higher pyridoxal-5'-phosphate (p = 0.0018) and urinary phosphoethanolamine (p = 0.0001) concentrations., Conclusions: Screening may detect mainly less severely affected individuals, which may nevertheless avoid misdiagnosis and inappropriate antiresorptive drug exposure. Patients with biallelic mutations had more severe symptoms, significantly lower ALP and higher substrate levels. Whether the latter finding has implications for the classification and treatment of HPP should be investigated further in larger cohorts., (Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Kidney transplant recipients are at increased risk of fractures. This prospective observational study investigated whether areal bone mineral density (aBMD) as assessed by dual-energy x-ray absorptiometry can predict incident fragility fractures in de novo kidney transplant recipients and whether bone turnover markers increase diagnostic accuracy. Parameters of bone mineral metabolism including parathyroid hormone (PTH), fibroblast growth factor 23, sclerostin, calcidiol and calcitriol, and bone turnover markers were assessed in blood samples collected immediately prior to kidney transplantation in 518 adult recipients. aBMD was measured at several skeletal sites within 14 days posttransplant. Thirty patients had a history of a fragility fracture at the time of transplantation, and osteopenia or osteoporosis at the femoral neck was observed in 77%. Bone turnover markers were inversely correlated with aBMD at all skeletal sites. Low aBMD and low PTH were associated with history of fragility fracture at the time of transplantation, independent of age, gender, and comorbidity. During a median post-transplant follow-up of 5.2 years, 38 patients sustained a fragility fracture, corresponding to a fracture incidence of 14.1 per 1000 person-years. Low aBMD at the hip and lumbar spine were associated with incident fractures, independent of classical determinants, including history of fracture. PTH and bone turnover markers at the time of transplantation failed to predict incident fractures. In conclusion, aBMD is low, correlates inversely with bone turnover, and predicts incident fractures in de novo kidney transplant recipients., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Bone and muscle are required for mobility but they also have endocrine and metabolic functions. In ageing as well as in many chronic diseases, bone loss and muscle atrophy occur simultaneously, leading to concomitant osteoporosis and sarcopenia. This occurs in both genders but compared with postmenopausal women, men appear to be better protected against age-related bone and muscle decay. Sex steroids (both androgens like testosterone and oestrogens like estradiol) are mainly responsible for musculoskeletal sexual dimorphism. They stimulate peak bone and muscle mass accretion during puberty and midlife, and prevent subsequent loss in ageing men but not post-menopausal women. Still, recent studies have highlighted the importance of intrinsic ageing mechanisms such as cellular senescence and oxidative stress in both genders. Sarcopenia may predispose to dysmobility, frailty, falls and fractures, but whether so-called osteosarcopenia qualifies as a distinct entity remains debated. Although randomized clinical trials in male osteoporosis are smaller and therefore underpowered for some outcomes like hip fractures, the available evidence suggests that the clinical diagnostic and therapeutic approach to male osteoporosis is largely similar to that in postmenopausal women. There is a clear unmet medical need for effective and safe anabolic drugs to rebuild the ageing skeleton, muscle, and preferably both tissues simultaneously. The Wnt/sclerostin and myostatin/activin receptor signalling pathways appear particularly promising in this regard. In this narrative review, we aim to provide an overview of our current understanding of the pathophysiology and treatment of male osteoporosis and sarcopenia, and interactions between these two diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Androgens via the androgen receptor (AR) are required for optimal male bone health. The target cell(s) for the effects of androgens on cortical bone remain(s) incompletely understood. In females, estrogen receptor alpha in neurons is a negative regulator of cortical and trabecular bone. Whether neuronal AR regulates bone mass in males remains unexplored. Here, we inactivated AR in neurons using a tamoxifen-inducible CreERT2 under the control of the neuronal promoter Thy1. Tamoxifen induced a 70% to 80% reduction of AR mRNA levels in Thy1-CreERT2-positive brain regions cerebral cortex and brainstem as well as in the peripheral nervous tissue of male neuronal AR knockout (N-ARKO) mice. Hypothalamic AR mRNA levels were only marginally reduced and the hypothalamic-pituitary-gonadal axis remained unaffected, as determined by normal levels of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). In contrast to orchidectomy, deletion of neuronal AR did not alter body weight, body composition, hindlimb muscle mass, grip strength, or wheel running. MicroCT analysis of the femur revealed no changes in bone accrual during growth in N-ARKO mice. However, 36- and 46-week-old N-ARKO mice displayed an accelerated age-related cortical involution, namely a more pronounced loss of cortical thickness and strength, which occurred in the setting of androgen sufficiency. Neuronal AR inactivation decreased the cancellous bone volume fraction in L 5 vertebra but not in the appendicular skeleton of aging mice. MicroCT findings were corroborated in the tibia and after normalization of hormonal levels. Serum markers of bone turnover and histomorphometry parameters were comparable between genotypes, except for a 30% increase in osteoclast surface in the trabecular compartment of 36-week-old N-ARKO mice. Cortical bone loss in N-ARKO mice was associated with an upregulation of Ucp1 expression in brown adipose tissue, a widely used readout for sympathetic tone. We conclude that androgens preserve cortical integrity in aging male mice via AR in neurons. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Background: Diagnosing polycystic ovary syndrome (PCOS) is based on ovulatory dysfunction, ovarian ultrasound data, and androgen excess. Total testosterone is frequently used to identify androgen excess, but testosterone is mainly bound to sex hormone-binding globulin (SHBG) and albumin. Only 1-2% of nonprotein-bound testosterone (so-called free testosterone) is biologically active and responsible for androgen action. Moreover, automated immunoassays which are frequently used for female testosterone measurements are inaccurate., Objective: To assess the clinical usefulness of liquid chromatography-tandem mass spectrometry measured testosterone and calculated free testosterone in subfertile women attending a fertility clinic with oligomenorrhea and suspected PCOS., Methods: Hormonal and metabolic parameters were evaluated, and ovarian ultrasound was performed. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Free testosterone was calculated from total testosterone and SHBG., Results: Sixty-six women were included in the study. Total testosterone was associated with ovarian volume and antral follicle count but not with metabolic parameters. However, SHBG and calculated free testosterone were associated with both ovarian ultrasound and metabolic parameters, such as BMI and insulin resistance., Conclusions: Assessing SHBG and free testosterone is important in evaluating androgen excess in subfertile women with ovulatory dysfunction and suspected PCOS, as it reflects both ovarian and metabolic disturbances.

Osteocyte lacunae are small cavities within the bone matrix. Their dimensions and spatial arrangement affect bone mechanical properties. Furthermore, their size and shape affect the strain in bone tissue close to the lacunae; hence, they are supposed to affect the mechanosensory function of the osteocytes residing in the lacunae. It was the purpose of this study to quantify the morphological features of osteocyte lacunae, whether these are affected by aging and whether these vary among different anatomical location. In addition, we aimed at quantifying the vascular canals as these affect bone's microporosity too. We quantified the microporosity in the fibular midshaft of young-adult and old female C57BL/6 mice. Using micro-computed tomography (μCT), we found that advanced age was associated with a significantly decreased vascular canal number and volume density. In aged mice, the mean volume of the lacuna was significantly smaller than in young animals and they were more round. Lacuna number density close to the neutral axis of the fibula was higher in older mice than in young ones. The characterization of bone microporosity presents a first step in further unraveling their potential role in age-related reductions in bone strength., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Physical inactivity is a pandemic that contributes to several chronic diseases and poses a significant burden on health care systems worldwide. The search for effective strategies to combat sedentary behavior has led to an intensification of the research efforts to unravel the biological substrate controlling activity. A wide body of preclinical evidence makes a strong case for sex steroids regulating physical activity in both genders, albeit the mechanisms implicated remain unclear. The beneficial effects of androgens on muscle as well as on other peripheral functions might play a role in favoring adaptation to exercise. Alternatively or in addition, sex steroids could act on specific brain circuitries to boost physical activity. This review critically discusses the evidence supporting a role for androgens and estrogens stimulating male physical activity, with special emphasis on the possible role of peripheral and/or central mechanisms. Finally, the potential translation of these findings to humans is briefly discussed., (© 2018 Society for Endocrinology.)

An overview of selected papers related to bone published in 2017 is provided., Purpose: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year., Methods: A PubMed search using the keyword "bone" and articles published in 2017., Results: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation. Other selected articles cover effectiveness of bisphosphonates and changes in mineralization after long-term use, new guidelines for glucocorticoid- and aromatase inhibitor-induced osteoporosis, increasing use of high-dose vitamin D supplements despite lack of evidence for their widespread high-dose use, and cardiovascular safety concerns surrounding the use of calcium supplements. Other topics discussed are effects of diabetes on bone health, reciprocal crosstalk between bone cells and adipose tissue, and resistance exercise training to prevent bone loss and sarcopenia., Conclusions: These papers offer a hopeful outlook for a better treatment and management of patients with osteoporosis and other metabolic bone diseases anno 2018.

Low testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of "low free T". Our results clearly show a fast and dramatic action of T stimulating wheel running, which is not explained by its action on muscle, as evidenced by neuromuscular studies and in a muscle-specific conditional ARKO mouse model. The action of T occurs via its free fraction, as shown by the results in SHBG-transgenic mice, and it implies both androgenic and estrogenic pathways. Both gene expression and functional studies indicate that T modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the restoration of wheel running by T is inhibited by treatment with DA antagonists. These findings reveal that the free fraction of T, both via AR and indirectly through aromatization into estrogens, stimulates physical activity behavior in male mice by acting on central DA pathways.

Patients with chronic kidney disease (CKD) are at increased risk of fractures. The fracture risk steadily increases along with the progression of renal disease to become several-fold higher in end-stage renal disease (ESRD) patients as compared to age and sex-matched controls. Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease. Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD, but do have important inherent limitations. The gold standard for the diagnosis and specific classification of renal osteodystrophy (ROD) remains the (quantitative) histomorphometric analysis of the bone biopsy. By informing on bone turnover and mineralization, a bone biopsy may help guide prevention and treatment of ROD and its consequences. This review aims to present an update on epidemiological and procedural aspects, clinical indications, and histomorphometric analysis of bone biopsies and to define the role of bone biopsy in current CKD-MBD care.

The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or antagonistic actions on several tissues, including bone. The off-target effects of tamoxifen are one of the most widely recognized pitfalls of tamoxifen-inducible Cre recombinases (CreERs), potentially confounding the phenotypic findings. Still, the validation of tamoxifen induction schemes that minimize the side effects of the drug has not been addressed. Here, we compared the side effects on the skeleton and other androgen-responsive targets of a shortened tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard protocol (4 doses) and determined their efficiency in inducing CreER-mediated gene deletion. In addition, both a vehicle- and a 10-dose group, which served as a positive control for tamoxifen side effects, were also included. For this purpose, we generated male mice with a floxed androgen receptor (AR) and a neuron-specifically expressed CreER. Treatment with two doses of tamoxifen was the only regimen that did not diminish androgenic bioactivity, as assessed by both seminal vesicles and levator ani/bulbocavernosus muscle weights and serum testosterone concentrations. Similarly, trabecular and cortical femoral bone structure were dramatically altered by both the standard and high-dose protocols but not by the shortened version. Serum osteocalcin and bone-gene expression analyses confirmed the absence of effects on bone by 2 doses of tamoxifen. This protocol decreased AR mRNA levels efficiently and specifically in the nervous system. Thus, we optimized a protocol for tamoxifen-induced CreER gene deletion in mice without off-target effects on bone and male reproductive organs., (Copyright © 2017 Elsevier B.V. All rights reserved.)