Management of hand osteoarthritis: from an US evidence-based medicine guideline to a European patient-centric approach.

Hand osteoarthritis is the most common joint condition and is associated with significant morbidity. It is of paramount importance that patients are thoroughly assessed and examined when complaining of hand stiffness, pain, deformity or disability and that the patient's concerns and expectations are addressed by the healthcare professional. In 2019 the American College of Rheumatology and Arthritis Foundation (ACR/AF) produced guidelines which included recommendations for the treatment of hand osteoarthritis. An ESCEO expert working group (including patients) was convened and composed this paper with the aim to assess whether these guidelines were appropriate for the treatment of hand osteoarthritis therapy in Europe and whether they met with the ESCEO patient-centered approach. Indeed, patients are the key stakeholders in healthcare and eliciting the patient's preference is vital in the context of an individual consultation but also for informing research and policy-making. The patients involved in this working group emphasised the often-neglected area of aesthetic changes in hand osteoarthritis, importance of developing pharmacological therapies which can alleviate pain and disability and the need of the freedom to choose which approach (out of pharmacological, surgical or non-pharmacological) they wished to pursue. Following robust appraisal, it was recommended that the ACR/AF guidelines were suitable for a European context (as described within the body of the manuscript) and it was emphasised that patient preferences are key to the success of individual consultations, future research and future policy-making.

Risk Factors, Manifestation, and Awareness of Osteoporosis among Patients of Various Specialists in Switzerland: Results of a National Survey.

Osteoporosis is the most common chronic metabolic bone disease, known to be underdiagnosed and undertreated in parts of the Swiss population. Due to expected rise in new fragility fractures, adequate awareness of associated risk factors and diagnostic and therapeutic options will be essential for the management of osteoporosis. We therefore explored these aspects in a nationwide survey of Swiss specialists and their patients. A total of 262 physician questionnaires and 9065 patient questionnaires were analyzed, mainly from general practitioners (64.9%), followed by rheumatologists (16.8%), gynecologists (12.2%), and endocrinologists (6.1%). Around 20% of patients were under medication and/or had a medical condition increasing the risk of osteoporosis. Further risk factors, such as low consumption of calcium-rich foods, smoking, elevated alcohol intake, and insufficient physical activity, were present across regions and medical fields. 53.9% of patients did not take calcium/vitamin D supplements; 3.5% reported having fragility fractures, and 7.3% received treatment for osteoporosis. Only 38.5% of surveyed patients knew of the chronic nature of osteoporosis, indicating rather low awareness in this population. Despite generally perceived relevance of osteoporosis for daily practice, aspects of its prevention and management varied across regions and medical fields. Raising awareness among patients and physicians will be vital for addressing osteoporosis on a national scale.

Fracture Risk Following an Atypical Femoral Fracture.

Atypical femoral fractures (AFFs) occurring during the course of osteoporosis treatment usually lead to discontinuation of anti-resorptive (AR) drugs. However, the risk of fracture after an AFF is unknown. We conducted a follow-up study of patients with AFF matched 1:3 for age and gender with patients with a peripheral major osteoporotic fracture (pMOF), in the setting of a fracture liaison service, to investigate the incidence of subsequent low-trauma fractures. Fifty-five patients with AFF (95% women, age [mean ± standard deviation] 75 ± 10 years, 89% exposed to AR drugs), followed for 6.2 ± 3.7 years, were compared to 165 matched controls with a pMOF (hip 85%) followed for 4.3 ± 2.6 years. During the follow-up, 38% of patients in the AFF group and 16% in the pMOF group received AR therapies. Continuation of AR drugs after an AFF was associated with contralateral AFF in 27% of subjects. The risks of new low-trauma, major osteoporotic and imminent (within 2 years) fractures, were similar between the two groups: incidence rate ratio (95% confidence interval [CI]) of subsequent fracture following AFF relative to pMOF, 1.30 (95% CI, 0.82-2.04), 1.28 (95% CI, 0.74-2.15), and 1.11 (95% CI, 0.54-2.15), respectively. Moreover, the risk of sustaining multiple fractures per participant was significantly increased among patients with AFF compared to pMOF (hazard ratio 1.48 [95% CI, 1.00-2.19]; p = 0.049). When taking mortality into account, the risk of subsequent fractures tended to be higher in the AFF group (sub-hazard ratio 1.42 [95% CI, 0.95-2.12]). In conclusion, patients who sustained an AFF are at high risk of subsequent fragility fractures, at least equal or even greater to the risk observed after a pMOF. However, continuation of AR drugs increases the risk of contralateral AFF. Therefore, optimal modalities for secondary fracture prevention after AFF require further evaluation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Romosozumab : a new treatment for severe osteoporosis]. / Romosozumab : un nouveau traitement de l'ostéoporose sévère.

Romosozumab is a monoclonal antibody against sclerostin. Its dual effect on bone is to increase formation and decrease resorption. Sub-cutaneous injections of romosozumab are administered monthly for one year and must be relayed with a bone resorption inhibitor. Romosozumab followed by denosumab is associated with high increase of bone mineral density and decrease of fragility fractures. Gain of bone mineral density and reduction of fragility fractures are more important with romosozumab as compared with alendronate. The increase in bone mineral density is higher with romosozumab as compared to teriparatide in patients previously treated with alendronate. The use of romosozumab (Evenity) is admitted for patients with high risk of fractures but without serious vascular events.

Le romosozumab est un anticorps monoclonal dirigé contre la sclérostine, dont le double effet osseux est de stimuler la formation et diminuer la résorption. Il s'administre en injections sous-cutanées mensuelles pendant une année et il doit être relayé par un traitement inhibiteur de la résorption osseuse. La séquence romosozumab puis dénosumab est associée à des gains densitométriques et à une réduction des fractures de fragilité de grande amplitude. La réponse densitométrique et l'effet antifracturaire sont plus marqués sous romosozumab que sous alendronate. L'augmentation de la densité minérale osseuse est plus importante sous romosozumab que sous tériparatide après traitement préalable par alendronate. Le romosozumab (Evenity) est approuvé pour des patients avec un risque élevé de fracture en l'absence de complications vasculaires sévères.

[Osteoporosis: Novel drug, new recommendations]. / Ostéoporose - Nouvelle molécule, nouvelles directives.

New recommendations from the Swiss Association against Osteoporosis (SVGO) concerning fracture risk stratification and treatment delineate two new risk categories : very high risk (FRAX 10-years probability of fracture at least 20 % above the usual intervention threshold) and imminent risk (major osteoporotic fracture in the last 2 years). In these patients, parenteral therapies are recommended first. Among them, romosozumab is now available in Switzerland and is indicated for 1 year in absence of cardiovascular contra-indications, followed by an anti-resorptive. Regarding denosumab, several studies indicate that post-treatment bone loss may be, at least partially, prevented by zoledronate. Finally, monitoring BMD changes and the T-score reached on any therapy could be used as an indicator of anti-fracture efficacy.

Les nouvelles directives de l'Association suisse contre l'ostéoporose proposent deux nouvelles catégories dans la stratification du risque fracturaire et du traitement : très haut risque (FRAX au moins 20 % au-dessus du seuil d'intervention pour l'âge) et risque imminent (fracture ostéoporotique majeure au cours des 2 dernières années). Chez ces patient·e·s, les thérapies parentérales sont indiquées en première intention. Parmi celles-ci, le romosozumab est maintenant disponible en Suisse et est indiqué pour 1 an en l'absence de contre-indication cardiovasculaire, suivi d'un antirésorptif. Concernant le dénosumab, plusieurs études ont démontré que la perte osseuse à l'arrêt peut être, au moins partiellement, prévenue par l'acide zolédronique. Finalement, le score-T atteint sous thérapie pourrait être un indicateur clinique de l'effet antifracturaire.

[Patients with imminent fracture risk†: which consequences for their management†?] / Patients à risque imminent de fractures†: quelles conséquences pour la prise en charge†?

Irrespective of their age, patients with recent fragility fracture have an increased risk of recurrence : this is the imminent fracture risk of multiple origins. As well the vertebral than the non-vertebral fractures are equally predictive of an increased and early fracture risk. Therefore, a fragility fracture is a strong signal for the clinicians to introduce a treatment against osteoporosis. Especially since most of the treatment have been shown to reduce quickly the incidence of fractures. To target easily patients with the highest risk of re-fractures would allow to improve our efficacy.

Indépendamment de leur âge, les patients qui ont récemment présenté une fracture de fragilité sont à risque élevé de récidive : c'est le risque imminent de fractures dont les causes sont multiples. Les fractures récentes, qu'elles soient vertébrales ou non vertébrales, sont prédictives d'un risque accru et précoce de récurrence. De ce fait, la survenue d'une fracture de fragilité est un signal fort pour le clinicien pour introduire un traitement anti-ostéoporotique. D'autant plus que la plupart des traitements disponibles sont capables de réduire précocement les fractures. Cibler aisément les patients les plus à risque de (re)fractures permettrait ainsi d'augmenter l'efficacité de notre prise en charge.

[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.

[Osteoporosis]. / Ostéoporose.

The risk for a second fracture within two years after a first one is high. Ten years denosumab treatment show favorable results with a risk of early vertebral fractures in patients with prevalent vertebral fractures when treatment is stopped. Teriparatide is more effective than risedronate to prevent vertebral and clinical fractures in high risk patients. Romosozumab acts as an anabolic agent in osteoporosis. Atypical femoral fractures associated with bisphosphonate treatment could be more frequent in patients with particular anatomical features. Management of osteoporosis treatment depends on the drug which is used and on the risk of fracture of the patient.

Le risque de deuxième fracture dans les deux ans qui suivent un premier épisode est élevé. Les résultats de dix ans continus de dénosumab sont favorables, mais son arrêt expose au risque de fractures vertébrales précoces, surtout en cas de fractures vertébrales prévalentes. Le tériparatide est plus efficace que le risédronate pour prévenir les fractures vertébrales et cliniques chez les patientes à très haut risque. Le romosozumab confirme son intérêt comme agent anabolique dans le traitement de l'ostéoporose. Les fractures fémorales atypiques sous bisphosphonates pourraient être favorisées par des caractéristiques anatomiques. L'algorithme décisionnel pour la prise en charge de l'ostéoporose dépend de la nature du traitement et du risque de fracture du patient.

Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO.

Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

[To where and until when handle the osteoporosis?] / Jusqu'où et jusqu'à quand traiter l'ostéoporose ?

Estrogen replacement therapy, selective modulators of the estrogen receptor (SERMs), bisphophonates and denosumab are antiresorptive therapies which can be used for several years. Teriparatide is still the only bone forming agent available, its use is limited to 24 months. Except the absence of new fragility fractures, there is no well defined target in the treatment of osteoporosis. Nevertheless persistence of high fracture risk (prevalent fractures and/or low BMD) on therapy indicates to maintain or intensify the treatment. On the contrary, if fracture risk is low, a « therapeutic window ¼ could be considered after treatment with bisphosphonates, whereas after denosumab a short course of another treatment may be necessary.

L'œstrogénothérapie substitutive, les modulateurs sélectifs du récepteur aux œstrogènes (SERM), les bisphosphonates et le dénosumab sont des inhibiteurs de la résorption osseuse qui peuvent être utilisés plusieurs années. Le tériparatide est le seul traitement ostéoformateur et son utilisation est limitée à 24 mois. Hormis l'absence de nouvelles fractures de fragilité, il n'y a pas de cible thérapeutique définie dans le traitement de l'ostéoporose. Néanmoins, la persistance sous traitement d'un haut risque de fracture (fractures prévalentes et/ou ostéodensitométrie basse), est une indication à poursuivre, voire intensifier la thérapie. Si le risque de fracture est bas, au contraire, une « fenêtre thérapeutique ¼ est envisagée pour les traitements dont la durée d'action est plus longue que leur période d'administration (bisphosphonates). Pour le dénosumab, un relais thérapeutique de courte durée est nécessaire.

[Osteoporosis]. / Ostéoporose.

After one year of treatment with denosumab, the incidence of fracture is lower in patients previously treated one year with romosozumab as compared with placebo. Cessation of denosumab injections is followed by a rebound of bone resorption, a decrease of bone mineral density and increased risk of multiple vertebral fractures. For safety reasons, odanacatib, an inhibitor of cathepsine K and consecutively of bone resorption will not be available. Abaloparatide, a PTHrp(Parathormon related protein) analog, decreases the incidence of vertebral and non vertebral fractures. In patients with diabetes, the incidence of fractures is increased mainly due to alterations quality of bone.

L'incidence des fractures est moindre après un an de traitement par dénosumab chez des patients préalablement traités par romosozumab pendant une année en comparaison de ceux initialement sous placebo. L'arrêt du dénosumab est suivi d'un rebond de la résorption osseuse avec diminution des densités osseuses et risque de survenue de fractures vertébrales multiples. Pour des raisons de sécurité d'emploi, l'odanacatib, un antirésorbeur inhibiteur de la cathepsine K, ne sera pas commercialisé. L'abaloparatide, un analogue de la PTHrp (protéine apparentée à la parathormone), réduit l'incidence des fractures vertébrales et non vertébrales. Celle des fractures de fragilité est augmentée chez les patients diabétiques en relation avec des altérations de la qualité osseuse.

Effects of bariatric surgery on bone.

Bariatric surgery currently relies on combinations of restrictive and malabsorptive procedures. Early decreases in bone mineral density (BMD) have been reported. However, the accuracy of dual-energy X-ray absorptiometry used to measure BMD can be diminished by the major weight loss, whereas quantitative computed tomography (QCT) measurements are less affected. The nutritional deficiencies induced by mixed bariatric surgery procedures, together with changes in hormones produced by adipocytes and/or the gastrointestinal tract, are often associated with elevations in serum levels of bone resorption markers. Although the data are limited, the incidence of fractures does not seem higher after bariatric surgery than in non-operated obese patients.

[Bone diseases]. / Maladies osseuses.

Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.

[Osteoporosis]. / Ostéoporose.

Bone events related to bariatric surgery remain controversial. Denosumab, used in osteoporosis treatment, is safe and efficient. Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent. Odanacatib, a cathepsin-K inhibitor, decreases bone resorption and reduces osteoporotic fracture risk. Denosumab, as bone resorption inhibitor, and Teriparatide, as anabolic agent, have been tested together in patients with osteoporosis. Calcium supplements and cardiovascular risk are still debated. Drug holiday, after long-term treatment with bisphosphonates, is not associated with an increased fracture rate in patients with moderate risk.

[Use of NSAIDs in traumatology]. / Du bon usage des AINS en traumatologie.

In traumatology, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used, due to their efficacy in controlling pain and safety profile. Nonetheless, experimental and retrospective studies about the use of NSAIDs in traumatology raise the question about a possible negative influence on bone remodeling through inhibition of prostaglandin synthesis. The results from these studies must be interpreted with caution, as bone repair can be influenced by several parameters. When used in the case of sprains or tendinitis, unwanted side effects of NSAIDs seem to be limited; on the other hand, benefits in terms of antalgic effect are less clear. We have conducted a review of the literature aimed to suggest practical solutions for the use of NSAIDs in traumatology.

[Osteoporosis]. / Ostéoporose.

The quality of the management of patients with osteoporosis varies by country. The recommendations of the Swiss Association against osteoporosis propose intervention thresholds based on the results of the FRAX tool. Despite increasing number of observational studies with several hundred thousands of patients, it is not possible to conclude to a clear increased risk of cardiovascular disease with calcium intakes. A persistent effect of zoledronic acid is observed even after one single injection. There is no increased fracture risk within 7 months following Denosumab treatment cessation.