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Context Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability. Objective and Methods Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum). Results Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice.

Purpose To provide a summarized state of the art of the relative efficacy and rapidity of action of pharmacological treatments to prevent imminent osteoporotic fractures. Methods We reviewed metanalyses (MA) and network metaanalyses (NMA) published during the last 10 years concerning the pharmacological treatment of osteoporosis. We compared the anti-fracture efficacy and the rapidity of action of various agents versus placebo and versus risedronate. Results All bisphosphonates decrease the incidence of vertebral fractures compared with placebo. Ibandronate is the only one without demonstrated efficacy against non-vertebral and hip fractures. Zoledronate, denosumab and anabolic therapy are associated with a higher fracture risk reduction than oral bisphosphonates. Compared with risedronate, which significantly reduces the rate of hip fractures, zoledronate, denosumab, teriparatide, abaloparatide and romosozumab are more efficient for vertebral fractures but not for non-vertebral or hip fractures reduction. No studies have compared bone anabolic treatments with zoledronate or denosumab. Oral bisphosphonates significantly reduce fracture risk only after more than one year of therapy. A faster reduction of fracture risk is observed with zoledronate and denosumab, or with anabolic agents. For denosumab and anabolic agents, a sequential treatment is required to keep gains after treatment withdrawal. Conclusions In patients at high risk of imminent fracture, starting therapy with potent antiresorptive agents or with an anabolic agent seems most appropriate to promptly reduce the fracture risk. Available NMA/MA suggest that, compared to zoledronate and denosumab, anabolic agents have a higher efficacy for vertebral fractures but head-to-head studies are lacking., Highlights • The concept of imminent fracture has implications for the choice of therapy • We reviewed metanalyses and network metaanalyses published in the last 10 years • We compared the efficacy and rapidity of treatments to prevent imminent fractures • Potent antiresorptive and anabolic agents are most appropriate to promptly reduce fracture risk • Anabolic agents seem to be more efficient to reduce vertebral fracture risk

Background: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) are the current standard-of-care for many advanced cancers (1). This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE). The underlying mechanisms are not yet fully understood. We explore the role of HLA in endocrinopathy related to ICI therapy using an interesting patient. Case presentation: A 63-year-old woman was diagnosed in May 2019 with stage IIIB non-small cell lung carcinoma of the right superior lobe with PD-L1 expression > 50%. The patient had a partial therapeutic response on two cycles of radio-chemotherapy with carboplatin and vinorelbine, with persistence of mild hypermetabolism in pulmonary nodules. She was started on consolidation immunotherapy with durvalumab (anti-PD-L1), 10 mg/kg every two weeks, with the intended treatment duration of one year. A routine blood sampling performed before the first chemotherapy showed normal thyroid function with a TSH 1.37 mU/L (reference range: 0.27-4.20) and free T4 19.0 pmol/l (reference range: 12.0-22.0). The thyroid function was not rechecked before the first durvalumab dosing. In December 2019, after three cycles, the patient presented herself at the pneumology department with fatigue, weight loss (2 kg in two months) and increased shortness of breath. Laboratory analysis showed a mild hyperthyroidism with decreased TSH (0.23 mU/L) and increased free T4 (29.4 pmol/l). Approximately 6 weeks later, levothyroxine 50 mg daily was started because of an evolution towards hypothyroidism (with TSH 37.90 mU/L; free T4 5.8 pmol/l), as shown in Figure 1. Thyroperoxidase antibodies were positive (216 kUI/L, reference range: < 34), while the TSH receptor antibodies (TRAb, analysis of stimulating and blocking) were negative. Ultrasound examination of the thyroid was normal. Thyroid scintigraphy was not performed. HLA analysis showed A*02, -; B*15,*40; C*03,*07; the DR haplotypes: DRB1*04,*13, and the DQ haplotypes: DQB1*03,*06. Discussion: This case report illustrates that more attention should be given to the immunogenetic background of oncology patients treated with immunotherapy (2). HLA polymorphisms have been implicated for ‘conventional’ autoimmune thyroid disease (AITD), such as DR4 (susceptible), DR7 and DR13 (protective) for Hashimoto, and DR3 (susceptible) for Graves’ disease. Our patient has a mixed HLA susceptibility, with the presence of both HLA-DR4 (susceptible) and DR13 (protective). A variety fo other HLA associations have been described in patients with endocrinopathy related to immune therapy, such as DR4 in diabetes mellitus; DR4-DQ4 and DR9-DQ9 in diabetes mellitus of Asian origin (3); HLA-A2, A24, B7, DR1 and DR4 (lymphocytic hypophysitis) in two cases of nivolumab-induced hypophysitis, DRB1*04 : 05-DQA1*03 :03-DQB1*04 :01 (autoimmune polyglandular syndrome with pituitary disorder in a Japanese population) in a patient with isolated adrenocorticotropin deficiency by nivolumab-induced hypophysitis. Conclusion: In summary, our case of patient with thyroiditis associated with the PD-L1 inhibitor durvalumab highlights not only the need for proactive monitoring of thyroid function, but also identifying biomarkers associated with an increased risk of ICI-induced side effects for better patient selection, optimal management and improved understanding of the mechanisms involved. References: 1. Sammamed MF, Chen L. A Paradigm Shift in Cancer Immunotherapy : From Enhancement to Normalization. Cell. 2018. 2. Correale P, Saladino RE, Nardone V, Giannicola R, Agostino R, Pirtoli L, et al. Could PD-1/PDL1 immune checkpoints be linked to HLA signature ? Immunotherapy. 2019. 3. De Filette JMK, Pen JJ, Decoster L, Vissers T, Bravenboer B, Van Der Auwera BJ, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus : A case report and systematic review. European Journal of Endocrinology. 2019.

Pituitary adenoma is a well-known cause of panhypopitutarism. The degree of hypopituitarism is variable ranging from a single hormone deficiency to a general disorder. The onset in most cases is in several months or even years, so it is often misrecognized and not adequately treated. The presenting symptoms are also extremely variable. Recurrent hypoglycemia due to growth hormone, adrenal and other counter regulatory hormone deficiency is a less well-known complication of hypopituitarism. Case

Introduction. – Les personnes âgées sont le plus souvent hospitalisées et subissent, dans le décours de l'hospitalisation, une perte d'autonomie fonctionnelle dans 30 à 50 % des cas. Seul un patient sur deux récupère son niveau fonctionnel de départ. Il est donc primordial de détecter les patients fragiles dès leur arrivée et d'orienter ceux-ci vers des unités gériatriques adaptées à leur prise en charge. Différents outils ont été élaborés pour identifier ces patients à risque : Identification of Seniors At Risk (ISAR) et le score hospitalier d'évaluation du risque de perte d'autonomie (SHERPA). L'ISAR prédit la mortalité, l'institutionnalisation et la réhospitalisation dans les six mois après une admission en urgence. Le SHERPA a été élaboré pour prédire le risque de déclin fonctionnel, trois mois après la sortie, des patients hospitalisés via les urgences. Objectif. – Comparer les possibilités d'application et d'acceptation de ces deux outils en salle d'urgence et comparer leur performance à détecter les patients fragiles. Matériel et méthode. – Étude prospective d'observation (novembre 2005–juillet 2006) incluant des personnes âgées de 65 ans et plus hospitalisées via les urgences. Les sujets provenant d'une maison de repos et de soins et ceux allant en réanimation ont été exclus. Les patients ont été évalués simultanément par les deux outils dans les 24 heures de l'admission et par le même évaluateur. Un patient est considéré « à profil gériatrique » si le score ISAR est supérieur ou égal à 2 et si le score SHERPA supérieur ou égal à 5. L'analyse statistique des résultats s'est basée sur le Chi2. Résultats. – Parmi 871 patients âgés consécutifs hospitalisés via les urgences, 516 (59 %) étaient évaluables. Les deux échelles ont été réalisées chez 201 patients, 85 % des patients présentaient un profil gériatrique selon ISAR, 63 % selon SHERPA. Une corrélation hautement significative (p < 0,0001) existe entre ces deux outils dans la cohorte étudiée. Conclusion. – Compte tenu de ses caractéristiques métriques, comparé à ISAR, nous préconisons l'utilisation du SHERPA pour définir le profil de risque de déclin fonctionnel d'un patient hospitalisé via les urgences. En pratique clinique, cet outil se révèle facile à utiliser et apporte des informations qui nous permettent de l'utiliser pour orienter les patients fragiles vers les services de gériatrie.