The Totality of Evidence for SDZ-deno: A Biosimilar to Reference Denosumab.

Purpose: Sandoz biosimilar denosumab (GP2411 [SDZ-deno]; Jubbonti/Wyost) is approved by the US FDA, EMA and Health Canada for all indications of reference denosumab (REF-deno; Prolia/Xgeva), a fully human IgG2κ monoclonal antibody that binds with high affinity and specificity to receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab blocks RANKL, preventing bone resorption and loss of bone density/architecture in conditions characterized by excessive bone loss such as osteoporosis in postmenopausal women and metastatic bone disease, among others.

Methods: This narrative review summarizes the totality of evidence (ToE) for SDZ-deno that supported its approval as Jubbonti/Wyost in the EU and US.

Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study.

Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26.

Risk factors predicting the 'time to first fracture' and its association with imminent fractures: a substudy of the FRISBEE cohort.

Unlabelled: Only previous glucocorticoid use and rheumatoid arthritis were predictors of an early fracture (< 2 years after inclusion). A shorter 'time to first fracture' was not an independent clinical risk factor for imminent fractures.

Purpose: Risk factors for fragility fractures independent of BMD were assessed in several prediction models.

Selection for treatment of patients at high risk of fracture by the short versus long term prediction models - data from the Belgian FRISBEE cohort.

Unlabelled: Our imminent model was less sensitive but more selective than FRAX® in the choice of treatment to prevent imminent fractures. This new model decreased NNT by 30%, which could reduce the treatment costs. In the Belgian FRISBEE cohort, the effect of recency further decreased the selectivity of FRAX®.

The effect of fracture recency on observed 5-year fracture probability: A study based on the FRISBEE cohort.

Introduction: Prediction models, especially the FRAX®, are largely used to estimate the fracture risk at ten years, but the current algorithm does not take into account the time elapsed after a fracture. Kanis et al. recently proposed correction factors allowing to adjust the FRAX® score for fracture recency.

Are there specific clinical risk factors for the occurrence of multiple fractures? The FRISBEE study.

Unlabelled: This study showed additional clinical risk factors for the occurrence of multiple fractures with regards to a single fracture, with often higher hazard ratios. It would be important to include the risk of the occurrence of multiple fractures in future prediction models.

Purpose: To identify clinical risk factors (CRFs) which would specifically increase the risk of multiple fractures.

External validation of FRISBEE 5-year fracture prediction models: a registry-based cohort study.

Unlabelled: Five-year fracture risk prediction from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) models was externally tested in 9716 Canadian women and demonstrated good discrimination but consistently overestimated risk.

Introduction: Five-year risk prediction models for all fractures, major osteoporotic fractures (MOFs) and central fractures (proximal to forearm and ankle) from the FRISBEE cohort demonstrated good performance in the original derivation cohort. Our aim was to externally validate the FRISBEE-based 5-year prediction models in routine practice.

Tumor-Induced Osteomalacia: A Systematic Clinical Review of 895 Cases.

Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO.

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

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults.

Distribution of Fracture Sites in Postmenopausal Overweight and Obese Women: The FRISBEE Study.

The association between obesity and fracture sites in postmenopausal women has been little studied. We examined the most common types of fractures in obese and overweight postmenopausal women compared to subjects with a normal BMI in the FRISBEE study, a cohort of postmenopausal women followed since 9.1 (7.

Fragility Fractures in Postmenopausal Women: Development of 5-Year Prediction Models Using the FRISBEE Study.

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).

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

Context: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ).

Impact of non-hip fractures in elderly women: a narrative review.

The association of hip fractures with adverse outcomes is well established, but for non-hip fractures this association still needs to be further investigated. The objective of this narrative review is to describe the state of the art with regards to the health impact of clinically relevant non-hip fracture locations in postmenopausal women. PubMed and Scopus databases were searched from January 2010 until December 2020.

Bariatric surgery and skeletal health: A narrative review and position statement for management by the European Calcified Tissue Society (ECTS).

Context: Numerous studies have demonstrated detrimental skeletal consequences following bariatric surgery.

Methods: A working group of the European Calcified Tissue Society (ECTS) performed an updated review of existing literature on changes of bone turnover markers (BTMs), bone mineral density (BMD), and fracture risk following bariatric surgery and provided advice on management based on expert opinion.

Literature Review: Based on observational studies, bariatric surgery is associated with a 21-44% higher risk of all fractures.

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

Probabilistic models including clinical risk factors with or without bone mineral density (BMD) have been developed to estimate the 5- or 10-year absolute fracture risk. We investigated the performance of the FRAX and Garvan tools in a well-characterized population-based cohort of 3560 postmenopausal, volunteer women, aged 60 to 85 years at baseline, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort, during 5 years of follow-up. Baseline data were used to calculate the estimated 10-year risk of hip and major osteoporotic fractures (MOFs) for each participant using FRAX (Belgium).

Prediction of an Imminent Fracture After an Index Fracture - Models Derived From the Frisbee Cohort.

Patients who sustain a fracture are at greatest risk of recurrent fracture during the next 2 years. We propose three models to identify subjects most at risk of an imminent fracture, according to fracture site (any fracture, major osteoporotic fracture [MOF] or central). They were constructed using data of the prospective Frisbee cohort, which includes 3560 postmenopausal women aged 60 to 85 years who were followed for at least 5 years.

MOF/Hip Fracture Ratio in a Belgian Cohort of Post-menopausal Women (FRISBEE): Potential Impact on the FRAX® Score.

The ratio between major osteoporotic fractures (MOFs) and hip fractures in the Belgian FRAX® tool to predict fractures is currently based on Swedish data. We determined these ratios in a prospective cohort of Belgian postmenopausal women. 3560 women, aged 60-85 years (70.

Osteoporosis management in hematologic stem cell transplant recipients: Executive summary.

Background: Treatment advances have reduced the adverse events associated with hematopoietic stem cell transplant (HSCT) and led to an increased number of transplants performed. HSCT patients are living longer with concerns on long-term outcomes. Bone fragility and fracture are at the forefront for long-term morbidities post-HSCT.

Updated guidance on the management of cancer treatment-induced bone loss (CTIBL) in pre- and postmenopausal women with early-stage breast cancer.

Introduction: Adjuvant endocrine therapy induces bone loss and increases fracture risk in women with hormone-receptor positive, early-stage breast cancer (EBC). We aimed to update a previous position statement on the management of aromatase inhibitors (AIs) induced bone loss and now included premenopausal women.

Methods: We conducted a systematic literature search of the medical databases from January 2017 to May 2020 and assessed 144 new studies.

Risk factors for imminent fractures: a substudy of the FRISBEE cohort.

Unlabelled: Multiple factors increase the risk of an imminent fracture, including a recent fracture, older age, osteoporosis, comorbidities, and the fracture site. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate treatment.

Introduction: The risk of a recurrent fragility fracture is maximal during the first 2 years following an incident fracture.

Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.

Context: Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients.

Methods: A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion.

Results: Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study.