Twenty-four months of follow-up in women with rebound-associated vertebral fractures after discontinuation of denosumab: a single-centre case series.

Evidence on the management of rebound-associated vertebral fractures after denosumab discontinuation is scarce. This study describes seven patients retreated with denosumab, teriparatide or zoledronate for 24 months. Their bone mineral density remained stable or improved and no new fractures occurred suggesting that all three options might be adequate for their treatment. PURPOSE: To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24 months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. METHODS: Patients with RAVFs who received retreatment (RT) for 24 months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24 months. RESULTS: Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24 months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24 months of follow-up, no patient suffered new fractures. CONCLUSION: In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24 months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study.

This study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management. INTRODUCTION: Quantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk. METHODS: One thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson's correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence. RESULTS: During a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18-1.75), 1.19 (0.99-1.43), and 1.52 (1.26-1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF. CONCLUSION: Heel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.

[Side effects of osteoporosis treatments: how to explain them to patients?] / Effets indésirables des traitements contre l'ostéoporose : comment les expliquer aux patient-e-s ?

Despite the effectiveness of osteoporosis treatments, fear of side effects reduces both their prescription by doctors, and their acceptance by patients. The most common side effects are benign and transient, such as flu-like symptoms after zoledronate infusion, or nausea and dizziness after teriparatide introduction. On the other hand, the dreaded osteonecrosis of the jaw is very rare and associated with known risk factors. Only vertebral fractures after stopping denosumab make this treatment a matter for experienced practitioners. Therefore, knowing the side effects of prescribed treatments and explaining them to patients is essential to promote adherence.

Malgré l'efficacité des traitements contre l'ostéoporose, la crainte de leurs effets indésirables diminue tant leur prescription par les médecins que leur acceptation de la part des patients. Les plus fréquents de ces effets indésirables sont pourtant bénins et transitoires, comme l'état pseudo-grippal après perfusion de zolédronate ou les nausées et vertiges à l'introduction du tériparatide. De l'autre côté, l'ostéonécrose de la mâchoire tant redoutée est très rare et associée à des facteurs de risque connus. Seules les fractures vertébrales à l'arrêt du dénosumab font que ce traitement soit à réserver aux praticien-ne-s qui en ont l'habitude. C'est pourquoi connaître les effets indésirables des traitements prescrits et les expliquer aux patient-e-s est essentiel pour favoriser l'adhésion thérapeutique.

[Osteoporosis: what's new in 2022]. / Ostéoporose : ce qui a changé en 2022.

The year 2022 has seen numerous studies: questioning the usefulness of vitamin D, the effect of osteoporosis treatments on mortality, and the benefit of parathyroidectomy on fractures in primary hyperparathyroidism. The efficacy of romosozumab is diminished by the treatments prescribed before its introduction. Finally, and fortunately, promising new molecules are available in various countries for the treatment of rare bone diseases.

L'année 2022 a vu de nombreuses études questionner l'utilité de la vitamine D et s'intéresser à l'effet des traitements de l'ostéoporose sur la mortalité ou encore au bénéfice de la parathyroïdectomie sur les fractures lors d'hyperparathyroïdie primaire. L'efficacité du romosozumab est diminuée selon les traitements prescrits avant son introduction. Finalement, et heureusement, de nouvelles molécules prometteuses sont disponibles dans différents pays pour le traitement des maladies osseuses rares.

[Does artificial intelligence have a role in osteoporosis management?] / L'intelligence artificielle a-t-elle un rôle dans la prise en charge de l'ostéoporose ?

The individual and societal burden of osteoporosis is high and will continue to increase due to the demographic situation. Applications based on artificial intelligence models can provide concrete solutions at each step of the management of osteoporosis: screening, diagnostic, therapy management and prognostic assessment. The implementation of such models could assist clinicians in their workflow while improving overall patient care.

L'ostéoporose représente un fléau important, à l'échelle individuelle mais aussi sociétale. Avec le vieillissement de la population, le nombre de patients concernés augmente de manière considérable. Des applications basées sur des modèles d'intelligence artificielle nous apportent des solutions de plus en plus concrètes, à chaque étape de la prise en charge de l'ostéoporose : dépistage, diagnostic, prise en charge médicamenteuse et évaluation pronostique. L'implémentation de tels modèles pourrait aider les professionnels de santé, aussi bien dans l'optimisation du flux du travail que dans la prise en charge clinique du patient.

[Systemic mastocytosis and bone impact]. / Mastocytose systémique et impact osseux.

Systemic mastocytosis is a rare disease characterized by the uncontrolled clonal proliferation of abnormal mast cells in one or more extracutaneous organs. It is no longer considered a myeloproliferative neoplasia but a distinct subgroup following the review of the classification by WHO in 2016. The average age at diagnosis is 60 years regardless of gender. Bone involvement, in the broad sense, is very common and often asymptomatic. Osteoporosis or bone fragility concerns approximately 20 % of cases. The particularity of bone damage directly induced by mast cell proliferation is its heterogeneity, sometimes combining osteolysis and osteosclerosis simultaneously. This makes the interpretation of paraclinical values (bone density, biomarkers) complex and the therapeutic attitude becomes a real challenge.

La mastocytose systémique est une maladie rare se caractérisant par la prolifération clonale incontrôlée de mastocytes anormaux dans un ou plusieurs organes extracutanés. La classification par l'OMS a été révisée en 2016 et ne la considère plus comme une néoplasie myéloproliférative mais comme un sous-groupe disctint. L'âge moyen au diagnostic est de 60 ans sans distinction de sexe. L'atteinte osseuse, au sens large, est très fréquente et souvent asymptomatique. L'ostéoporose ou fragilité osseuse concerne environ 20 % des cas. La particularité de l'atteinte osseuse directement induite par la prolifération mastocytaire est son hétérogénéité, mêlant ostéolyse et ostéosclérose parfois simultanément. Cela rend l'interprétation des valeurs paracliniques (densité osseuse, biomarqueurs) complexe et l'attitude thérapeutique devient un vrai challenge.

[Constitutional diseases of bone: clinical flags]. / Quand penser à une maladie osseuse constitutionnelle ?

Constitutional diseases of bone form a heterogeneous group of rare diseases of varied phenotypic presentations with a vast genetic heterogeneity. Detected mostly in childhood, they may also be diagnosed in adulthood. Medical history, clinical examination as well as biological and radiological investigations may lead to the diagnosis, which should be confirmed genetically. Joint limitations, early osteoarthritis, hip dysplasia, bone deformity, enthesopathies, bone fragility or a small height can be warning signs of a constitutional disease of bone. Establishing the diagnosis is crucial to enable optimal medical management with a specialized multidisciplinary team.

Les maladies osseuses constitutionnelles constituent un groupe hétérogène de maladies rares de présentations phénotypiques variées et d'une grande hétérogénéité génétique. Le plus souvent détectées dans l'enfance, elles peuvent également être diagnostiquées à l'âge adulte. L'anamnèse, l'examen clinique et les bilans biologiques et radiologiques permettent d'orienter le diagnostic, qui devra être confirmé par une analyse génétique. Les limitations articulaires, l'arthrose précoce, les dysplasies de hanches, les déformations osseuses, les enthésopathies ou la fragilité osseuse ainsi qu'une petite taille sont des signes d'alerte pour rechercher une maladie osseuse constitutionnelle. Établir le diagnostic est crucial pour permettre une prise en charge optimale, multidisciplinaire et spécialisée.

Quantitative Ultrasound (QUS) in the Management of Osteoporosis and Assessment of Fracture Risk: An Update.

Quantitative ultrasound (QUS) presents a low cost and readily available alternative to DXA measurements of bone mineral density (BMD) for osteoporotic fracture risk assessment. It is performed in a variety of skeletal sites, among which the most widely investigated and clinically used are first the calcaneus and then the radius. Nevertheless, there is still uncertainty in the incorporation of QUS in the clinical management of osteoporosis as the level of clinical validation differs substantially upon the QUS models available. In fact, results from a given QUS device can unlikely be extrapolated to another one, given the technological differences between QUS devices. The use of QUS in clinical routine to identify individuals at low or high risk of fracture could be considered primarily when central DXA is not easily available. In this later case, it is recommended that QUS bone parameters are used in combination with established clinical risk factors for fracture. Currently, stand-alone QUS is not recommended for treatment initiation decision making or follow-up. As WHO classification of osteoporosis thresholds cannot apply to QUS, thresholds specific for given QUS devices and parameters need to be determined and cross-validated widely to have a well-defined and certain use of QUS in osteoporosis clinical workflow. Despite the acknowledged current clinical limitations for QUS to be used more widely in daily routine, substantial progresses have been made and new results are promising.

[Osteoporosis]. / Ostéoporose.

The year 2021 is marked by several articles aimed at better risk stratification of osteoporosis to define the groups of patients at very high risk of fractures or at imminent risk of fractures. This stratification determines who should benefit from a first line bone anabolic treatment. A review of the current state of osteoporosis was therefore essential; it shows that Switzerland is lagging. In terms of prevention of bone fragility, dairy products are probably a leading strategy, especially in the elderly. The practical management of denosumab discontinuation is finally better understood. Finally, with the arrival of a new treatment, Burosumab, we are experiencing a therapeutic revolution for rare hypophosphatemic diseases.

L'année 2021 est marquée par des articles visant à une meilleure stratification du risque d'ostéoporose pour définir les groupes à très haut risque ou à risque imminent de fractures. Cette stratification détermine qui doit bénéficier d'un traitement anabolisant osseux en première ligne. Un état des lieux de l'ostéoporose était donc indispensable ; il montre que la Suisse accuse un certain retard. En termes de prévention de la fragilité osseuse, les produits laitiers sont probablement une stratégie de premier plan, notamment chez les personnes âgées. La gestion pratique de l'arrêt du dénosumab est enfin mieux comprise. Finalement, grâce à l'arrivée d'un nouveau traitement, le burosumab, nous vivons une révolution thérapeutique pour les maladies rares hypophosphatémiques.

Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort.

Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = - 0.153, p < 0.001) and sc-8PM (r = - 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

[Screening and management of sarcopenia by the general practitioner]. / Dépistage et prise en charge de la sarcopénie au cabinet.

Sarcopenia is an aging syndrome with multiple contributing factors, characterized by a loss of muscle strength, function and mass. It affects a third of the elderly population, increasing morbidity and mortality, as well as health costs. It should be suspected in the event of a decrease in physical capacities reported or observed during the consultation, in a patient with risk factors. Five questions (SARC-F formulary) or the measure of the gait speed makes screening easy to perform ; the diagnosis is confirmed by supplementary examinations in a specialized center. Treatment consists on performing physical exercises against resistance and ensuring sufficient caloric and protein intake; drug treatments are under study.

La sarcopénie est un syndrome lié au vieillissement avec de multiples facteurs favorisants, caractérisé par une perte de la force, de la fonction et de la masse musculaires. Elle affecte un tiers de la population âgée, chez qui elle augmente la morbidité et la mortalité ainsi que les coûts de la santé. On doit la suspecter en cas de diminution des capacités physiques rapportée ou observée lors de la consultation chez un patient présentant des facteurs de risque. Cinq questions (formulaire SARC-F) ou la mesure de la vitesse de la marche rendent facile le dépistage ; le diagnostic est confirmé par des examens complémentaires dans un centre spécialisé. La prise en charge consiste en la réalisation d'exercices physiques contre résistance en assurant des apports caloriques et protéiques suffisants ; des traitements médicamenteux sont à l'étude.

[Vitamin D and pregnancy]. / Vitamine D et grossesse.

Vitamin D deficiency affects more than half of the general population. During pregnancy vitamin D insufficiency is associated with a higher risk of complications such as an increased incidence of miscarriages. Preterm delivery, preeclampsia, gestational diabetes, growth retardation and low birth weight as well as postpartum hemorrhage are all pathologies whose incidence seems to be increased with hypovitaminosis D. This could be linked to the pregnancy changes of the immune system, on which vitamin D plays a well-known modulating role. Substitution, even if its benefit is not clearly established, should be considered as there are no side effects. Although lack of evidence regarding the timing of the introduction of treatment, substitution may be proposed before conception.

Un déficit en vitamine D concerne plus de la moitié de la population générale. Une carence en vitamine D en cours de grossesse est associée à une augmentation du risque de complications comme les fausses couches. Les accouchements prématurés, la prééclampsie, le diabète gestationnel, le retard de croissance et le petit poids de naissance ainsi que les hémorragies du post-partum sont toutes des pathologies dont l'incidence semble augmentée lors d'hypovitaminose D. Cela pourrait être en lien avec la modification du système immunitaire lors de la grossesse, sur lequel la vitamine D joue un rôle modulateur. Ainsi, même si son effet bénéfique n'est pas clairement établi et que les évidences concernant le moment de son introduction manquent, une substitution en vitamine D devrait être proposée en préconceptionnel.

[Towards an individualized bone health report focused on the patient - Bone parameters and treatment options]. / Vers un rapport de santé osseuse individualisé centré sur le patient - Les paramètres osseux et les possibilités de traite.

This article presents a novel approach of osteoporosis management, starting from the DXA scans performance, image quality, BMD and TBS assessment and interpretation, vertebral fracture assessment, decision making on treatment initiation and being finalized with patient`s further follow-up recommendations. A report based on this approach is soon to be implemented by the CiMO at CHUV. Among the thorough evaluation of the densitometric status of the patient, this report presents the first effort to incorporate into the osteoporosis clinical workflow the current evidence on TBS. It suggests practical ways to use TBS as in conjunction with BMD T-score or FRAX score to come up with the final scores that allow treatment initiation. Implementations in other non-Caucasian or non-Swiss clinical settings are to be accompanied by local validations.

Cet article présente une approche nouvelle de la prise en charge de l'ostéoporose, à partir de la performance des DXA, de la qualité de l'image, de l'interprétation combinée de la densité minérale osseuse et du TBS, de la recherche des fractures vertébrales, de la décision de traiter et des stratégies de suivi du patient. Un nouveau rapport densitométrique basé sur cette approche sera bientôt mis en fonction par le Centre interdisciplinaire des maladies osseuses du CHUV. Il présente le premier effort pour incorporer dans le flux de travail clinique de l'ostéoporose les toutes dernières avancées sur le TBS. Il suggère des moyens pratiques pour utiliser le TBS en conjonction avec le T-score de la DMO ou le FRAX pour obtenir les scores finaux en vue d'initier un traitement spécifique pour un profil de risque individuel donné. L'utilisation dans d'autres contextes cliniques non caucasiens/suisses devra être validée.

Sixty spontaneous vertebral fractures after denosumab discontinuation in 15 women with early-stage breast cancer under aromatase inhibitors.

PURPOSE: At denosumab discontinuation, bone turnover markers increase and the gained BMD is lost. In postmenopausal osteoporosis, there is an increased risk of spontaneous vertebral fractures (VFs) of about 1 to 10%, rarely described in women under denosumab for aromatase inhibitors (AI)-treated breast cancer. We aim to describe the characteristics of 15 patients under denosumab given for AI-treated early-stage breast cancer that presented VFs at its discontinuation. METHODS: Single-center retrospective case series of 15 patients. We report clinical data, dual X-ray absorptiometry values at denosumab initiation and discontinuation, and serum B-crosslaps dosage at the time of VF occurrence (before denosumab resumption). RESULTS: Fifteen women (66.4 ± 7.1 years at denosumab discontinuation) that received AI for 5.0 ± 0.6 years, denosumab 60 mg for 8.2 ± 2.0 doses, and developed 60 VFs at denosumab discontinuation, were followed for 24.4 ± 9.5 months. Patients suffered from 1 to 11 (mean 4.0 ± 1.9) clinical VFs within 7 to 16 months after last denosumab injection. VFs developed earlier in patients with longer denosumab treatment (R2 = 0.29, p = 0.04) and in patients without osteoporosis before denosumab (9.4 ± 2.0 vs. 13.0 ± 2.0 months; p = 0.005). Serum B-crosslaps at the time of VFs tended to be higher in patients with earlier VFs (R2 = 0.47; p = 0.06) or with longer denosumab treatment (R2 = 0.48; p = 0.06). Denosumab was resumed in all patients, then switched for a bisphosphonate in eight. No new VFs occurred during follow-up. CONCLUSIONS: Despite an apparently low fracture risk, women under denosumab for AI-treated early-stage breast cancer develop spontaneous VFs at denosumab discontinuation. This risk increases with treatment duration and may be prevented by a potent bisphosphonate.

Hepatosplenomegaly, pneumopathy, bone changes and fronto-temporal dementia: Niemann-Pick type B and SQSTM1-associated Paget's disease in the same individual.

Data from exome sequencing show that a proportion of individuals in whom a genetic disorder is suspected turn out to have not one, but two to four distinct ones. This may require an evolution in our diagnostic attitude towards individuals with complex disorders. We report a patient with splenomegaly, pneumopathy, bone changes and fronto-temporal dementia (FTD). "Sea-blue histiocytes" in his bone marrow pointed to a lysosomal storage disease. Homozygosity for a pathogenic mutation in the SMPD1 gene confirmed Niemann-Pick disease type B (NPD-B). Mild cognitive impairment and abnormal brain FDG PET were consistent with FTD. We initially tried to fit the skeletal and neurologic phenotype into the NPD-B diagnosis. However, additional studies revealed a pathogenic mutation in the SQSTM1 gene. Thus, our patient had two distinct diseases; NPD-B, and Paget's disease of bone with FTD. The subsequent finding of a mutation in SQSTM1 gene ended our struggle to explain the combination of findings by a singular "unifying" diagnosis and allowed us to make specific therapeutic decisions. SQSTM1 mutations have been reported in association with FTD, possibly because of defective autophagy. Bisphosphonates may be beneficial for PDB, but since they are known to inhibit acid sphingomyelinase activity, we refrained from using them in this patient. While the principle of looking for unifying diagnosis remains valid, physicians should consider the possibility of co-existing multiple diagnoses when clinical features are difficult to explain by a single one. Accurate diagnostic work-up can guide genetic counseling but also lead to better medical management.

[What can we do at the discovery of an osteroporotic vertebral fracture†?] / Que faire face à une fracture vertébrale ostéoporotique†?

Osteoporotic vertebral fractures (VF) are common and can induce acute and chronic pain, having a negative impact on quality of life and lifespan. One man and one women over five will have one or more osteoporotic VF after the age of 50. The screening of these fractures is important because they are predictive of subsequent fractures. Most of the vertebral fractures are asymptomatic and therefore under-diagnosed. Clinics is the first screening tool and radiologic imaging will confirm any suspicion. The initiation of anti-fracture treatment is crucial to avoid future fractures. Physiotherapy and analgesics are part of the management of pain as well as vertebroplasty or kyphoplasty.

Les fractures vertébrales (FV) ostéoporotiques sont fréquentes et sont à l'origine de douleurs aiguës et chroniques ayant un impact important sur la qualité et la durée de vie. Un homme et une femme sur cinq présenteront une ou plusieurs FV ostéoporotiques après l'âge de 50 ans. Le dépistage de ces fractures est important car elles sont fortement prédictives de fractures subséquentes. La majorité des FV (> 60 %) sont asymptomatiques donc sous-diagnostiquées. L'examen clinique est le premier outil de dépistage des FV et les différentes imageries permettront de confirmer le diagnostic. L'initiation d'un traitement anti-fracturaire est primordiale afin d'éviter de futures fractures. La physiothérapie et les traitements antalgiques aideront à la gestion de la douleur, parfois renforcée par la vertébroplastie ou la kyphoplastie.

[How to manage the rebound effect at denosumab discontinuation and avoid multiple vertebral fractures?] / Comment gérer l'effet rebond à l'arrêt du dénosumab et éviter les fractures vertébrales multiples†?

Denosumab discontinuation is associated with a severe rebound effect combining elevation of bone remodeling markers for two years and loss of the gained bone density. In the absence of a potent bisphosphonate prescription at denosumab discontinuation, multiple vertebral fractures are frequent. The median number of vertebral fractures is 5, within 7 to 20 months (median 11) after the last denosumab injection. A potent bisphosphonate prescribed at denosumab discontinuation may reduce this risk. This strategy requires close monitoring of bone remodeling markers and adjustment of treatment if bone remodeling is not controlled.

L'arrêt du dénosumab est associé à un effet rebond sévère associant élévation des marqueurs du remodelage osseux pour deux ans et perte du gain de densité osseuse. A l'arrêt du dénosumab, en l'absence de prescription d'un puissant bisphosphonate, la fréquence des fractures vertébrales multiples est élevée. Le nombre médian de fractures vertébrales est de 5 dans les 7 à 20 mois (médiane 11) suivant la dernière injection de dénosumab. Un bisphosphonate puissant prescrit à l'arrêt du traitement de dénosumab pourrait réduire ce risque. Cette stratégie nécessite un suivi serré des marqueurs du remodelage osseux et un ajustement du traitement si le remodelage osseux n'est pas suffisamment contrôlé.

[Menopausal hormone therapy. Effects on bone and body composition]. / Traitement hormonal de la ménopause†: effets osseux et sur la composition corporelle.

Changes occurring at menopause can be mitigated by prescribing menopausal hormone replacement therapy (HRT). Recent publications from the CoLaus/OsteoLaus cohorts provide important insights into the effects of HRT and after its discontinuation on bone and body composition. HRT has a beneficial effect on bone mineral density, bone microarchitecture and fracture prevention. The benefits persist after treatment discontinuation, but not beyond 2 to 5 years. The effect of HRT on body composition is more controversial. HRT reduces the accumulation of fat mass, mainly abdominal and visceral fat mass. This is important from the perspective of diabetes and cardiovascular disease prevention. However, the benefits seem to disappear immediately after discontinuation.

Les changements survenant à la ménopause peuvent être atténués par le traitement hormonal de la ménopause (THM). Les résultats récents issus des cohortes CoLaus/OsteoLaus apportent un éclairage important sur les effets du THM et de son arrêt sur les paramètres osseux et de la composition corporelle. Le THM a un effet bénéfique sur la densité minérale osseuse, la microarchitecture osseuse et la prévention des fractures. Le bénéfice persiste à l'arrêt du traitement, mais pas au-delà de 2 à 5 ans. L'effet du THM sur la composition corporelle est plus controversé. Le THM diminue l'accumulation de masse grasse, essentiellement de masse grasse abdominale et intraviscérale. Ceci est important dans la perspective de la prévention du diabète et des maladies cardiovasculaires. Par contre, le bénéfice semble disparaître à son arrêt.

[Phosphocalcic anomalies and bone fragility keys for the general practitioner]. / Bilan phosphocalcique perturbé dans le cadre d'une fragilité osseuse : des clés pour le praticien.

How to recognize secondary causes of bone fragility in relation with an abnormal calcium and phosphate laboratory in general practice ? Through clinical cases presentations we will discuss the calcium and phosphate abnormalities which can be related to bone fragility and for which a-specific approach must be proposed. It can be abnormal results of calcium, phosphate or vitamin D. Some causes are frequent, others are iatrogenic, and others are related to a rare disease sometimes of genetic cause which consequences are more important than expected.

Comment reconnaître les causes secondaires de fragilité osseuse liées à un bilan phosphocalcique perturbé au cabinet ? A travers des vignettes cliniques, nous aborderons les désordres phosphocalciques qui peuvent être à l'origine d'une fragilité osseuse et pour lesquels une prise en charge indépendante doit être proposée. Il peut s'agir de la découverte d'une anomalie du calcium, du phosphate ou de la vitamine D. Certaines causes sont fréquentes, d'autres iatrogènes, et d'autres débouchent sur le diagnostic d'une maladie rare parfois de cause génétique dont les conséquences sont plus importantes que prévu.