The Build Better Bones website was developed using a robust stakeholder-engaged approach to be a self-management resource for people with osteoporosis and for care partners of people with osteoporosis. The website focuses on providing education and resources for exercise, nutrition, home safety, and advice for care partners. INTRODUCTION:Osteoporosis is a common chronic disease that requires effective self-management, including optimal diet, exercise, and home safety practices. The COVID-19 pandemic disrupted traditional outpatient care and increased the need for remote resources. In response, the International Osteoporosis Foundation (IOF) Rehabilitation Working Group developed a web-based platform "Build Better Bones" to support individuals with osteoporosis and their care providers. METHODS:The website's development followed a design thinking, iterative process informed by input from diverse stakeholders, including patients, healthcare professionals, and design experts. Qualitative feedback from 24 stakeholders across three countries shaped the platform's usability and content. Key features include an evidence-based exercise library, practical nutritional guidance, and home safety recommendations. To ensure inclusivity, the site was designed to accommodate a global audience through translation into five languages and culturally diverse animated characters. RESULTS:Stakeholders emphasized the primacy of site navigation and readability, empowering and inclusive images, and compassionate language. The website provides exercises tailored to the management of osteoporosis, focusing on exercise and nutrition with an emphasis on home safety to minimize the risk of fracture. The inclusion of interactive elements, multilingual support, and visually appealing content was guided by stakeholder input. Patients identified the accordion-style presentation and focus on empowering self-management, while clinicians valued the evidence-based exercise recommendations. Qualitative input highlighted the need for inclusive language, accessibility improvements, and practical guidance for safe practice at home. CONCLUSION:The "Build Better Bones" platform bridges a gap in osteoporosis care by providing evidence-based resources tailored to both clinicians and patients that can be disseminated to a global audience. Iterative stakeholder feedback has ensured that the platform is aligned with user needs, making it scalable and adaptable to real-world conditions. Future efforts will focus on expanding content, improving tailored features, and integrating additional languages to serve a global audience.

This expert position statement reframes arthroplasty and spinal fusion complications under the unified endpoint of implant fixation failure, defined as loss of mechanical integrity of the bone–implant unit over time. It synthesizes mechanistic and clinical evidence and provides evidence-informed recommendations for peri-operative bone health optimization. Osteoporosis is traditionally conceptualized as causing fragility fractures. However, compromised bone quality also affects the integrity of bone–implant constructs, influencing whether implants maintain fixation, interfaces remain stable, and fusion constructs consolidate. To synthesize mechanistic, translational, and clinical evidence on how osteoporosis and osteoporosis pharmacotherapies influence implant fixation failure across arthroplasty and spinal fusion, and to provide evidence-informed clinical recommendations for peri-operative bone health assessment and optimization within a unified construct-level framework. A position statement was developed following a structured literature search. Evidence was synthesized narratively by defining implant fixation failure as a construct-level outcome encompassing periprosthetic fracture, loosening, subsidence, pseudarthrosis, and junctional failure. Recommendations were categorized by strength (strong or conditional) and certainty of evidence (high, moderate, or low). Low bone mineral density (BMD) is associated with implant fixation failure across arthroplasty and spinal fusion. In arthroplasty, randomized trials demonstrate preservation of periprosthetic BMD with bisphosphonates, while registry analyses suggest improved implant survival. In spinal fusion, antiresorptive and anabolic therapies influence fixation-related parameters, with anabolic agents showing the most consistent evidence for enhanced fusion mass and earlier union. Much of the literature relies on radiographic or biomechanical endpoints rather than definitive outcomes. Viewing arthroplasty and spinal fusion complications through a shared construct-level perspective provides a coherent link between osteoporosis and reconstructive durability. Systematic peri-operative bone health optimization may improve construct longevity, although more definitive outcome-driven trials are needed. Closer integration between orthopedic surgeons and osteoporosis specialists will be central to advancing peri-operative bone health care.

Hyaluronic acid (HA) is a linear polysaccharide which occurs naturally as a constituent of synovial fluid. The HA concentration in the joint decreases inexorably during the progression of knee osteoarthritis (OA) and so, for nearly five decades, HA has been trialled and used in the treatment of knee OA. There are strong data from clinical trials, meta-analyses and umbrella reviews to support the use of intra-articular hyaluronic acid (IAHA) in the treatment of patients with knee OA, though not in patients with acute, active OA experiencing a flare. The majority of the literature suggests that IAHA has a positive safety profile despite a few meta-analyses suggesting an increased risk of serious adverse effects. Further qualitative analysis integrating patient preferences for multi-modal and/or non-surgical management is required in order to further explore these findings. IAHA has been combined with a number of additional agents, including mannitol, sorbitol, chondroitin sulphate, tranexamic acid, polynucleotides and hybrid IAHA formulations. These show variable performance beyond the baseline effect of their constituents. It is crucial to consider the patient’s preference when considering treatments for knee OA. Specific to IAHA, patients seek minimally invasive, lower-risk, and non-steroidal options with at least moderate efficacy and advantageous safety profiles. Hyaluronic acid is a naturally occurring constituent of synovial fluid and there are strong studies supporting its use in the treatment of osteoarthritis (outside the context of disease flares). The majority of literature supports a highly advantageous safety profile for hyaluronic acid in terms of adverse effect profile. Intra-articular hyaluronic acid (IAHA) can be injected in combination with other agents; including mannitol, sorbitol, chondroitin sulphate, tranexamic acid, polynucleotides and hybrid IAHA formulations, which show potential efficacy beyond their constituents alone.

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

Physical activity (PA) and sedentary behavior (SB) are two key lifestyle factors with profound implications for bone health across the lifespan. While PA is recognized for its positive effects on bone mineral density (BMD) and fracture prevention, emerging evidence highlights the detrimental consequences of prolonged sedentary time, independent of PA levels. This review synthesizes current knowledge on the impact of PA and SB on bone health outcomes, focusing on BMD and fracture risk in children, adolescents, adults, and older populations. A selection of epidemiological studies, systematic reviews, and meta-analyses was analyzed to explore the associations between movement behaviors and bone health indicators across different life stages. Particular attention was given to studies objectively measuring SB and PA and to the substitution effects of sedentary time with light or moderate-to-vigorous PA. In children and adolescents, higher levels of SB are associated with lower BMD, particularly at weight-bearing sites, while participation in weight-bearing and impact-loading PA positively influences bone mass accrual. In adults and older individuals, regular PA, including moderate-to-vigorous intensity weight-bearing PA and resistance training activities, is consistently linked to greater BMD and reduced fracture risk. Conversely, high sedentary time is associated with lower BMD and increased fracture incidence, particularly among frail or pre-frail individuals. Importantly, replacing sedentary time with even light-intensity PA yields measurable benefits for bone health, particularly among older adults and postmenopausal women, and may contribute to a reduced risk of fractures, although evidence remains limited. Promoting PA while minimizing SB should be central to clinical practice and public health policies aimed at maximizing and preserving skeletal health and preventing osteoporotic fractures, across the lifespan. Early intervention, continuous promotion across life stages, and adherence to WHO guidelines offer an effective, evidence-based framework for lifelong bone health maintenance.

Parathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.

Knee osteoarthritis is a highly prevalent whole-joint disease that is associated with substantial morbidity. If step changes are to be made in the management of knee osteoarthritis, novel patient stratification approaches are needed to identify the most effective treatment for individual patients. Numerous methods for stratifying patients with knee osteoarthritis can be employed; clinical presentation, including co-morbidity and pain phenotype, can influence treatment decisions, and there is a rich history of imaging biomarker use, both from conventional radiographs and, since its development, via MRI, in identifying patients at risk of disease progression, and the latter facilitates the detection of synovitis. The development of novel biochemical biomarkers and the rapid growth of ‘-omics’ technologies provide fresh opportunities to deploy these advances in the stratification of patients with knee osteoarthritis. The health economic landscape in this area is developing, and scoping work has highlighted the need for further studies. This Perspective article discusses the stratification of patients with knee osteoarthritis (OA) in the context of current guidelines, biomarkers and emerging and future developments of targeted treatment. The authors aim to highlight how these novel developments can enhance the stratification of patients with knee OA to improve patient outcomes.

The longitudinal impact of fractures associated with osteoporosis on costs and health-related quality of life is not well understood. The objective of this study was to characterize these outcomes over an 18-mo period following 4 common fracture types. Patients aged over 50 yr at 7 study sites with a diagnosis of incident hip, distal radius, proximal humerus, or vertebral fracture were enrolled in the International Costs and Utilities Related to Osteoporotic Fracture Study US. Data collection by questionnaire occurred at baseline (within 6 wk of fracture), 4-, 12-, and 18-mo post-fracture. Direct, indirect, and total costs were estimated over an 18-mo period and are reported in 2020 US Dollars. Health utilities were measured using EuroQol EQ-5D and the SF-6D. We performed longitudinal regression models of estimated costs adjusted for age and sex. We enrolled 284 patients with single fragility fractures (58 hip, 50 distal radius, 32 proximal humerus, 144 vertebral). Mean ages were 68.1 yr for distal radius and proximal humerus and 76 yr for hip patients. Most participants were women (76%-84% women). Over the 18-mo study period, direct costs (Including initial fracture and fracture related follow-up costs) were $18 495 for hip, $3451 for distal forearm, $6009 for humerus, and $9274 for vertebral fracture. Mean indirect costs were $9250 for hip, $1772 for distal radius, $4195 for humerus, and $4084 for vertebral fracture. Adjusted mean EQ-5D differences (95% CI) at 18-mo for those surviving/reporting compared with baseline were: hip −0.162 (95% CI, −0.22 to −0.103), distal radius −0.017 (95% CI, −0.056 to 0.022), proximal humerus −0.064 (95% CI, −0.103 to −0.0248), and vertebral −0.044 (95% CI, −0.083 to −0.0048). Substantial direct and indirect costs are observed in the 18-mo following 4 common osteoporotic fractures. Significant changes in health utility persisted for all fractures other than distal radius fractures regardless of the health utility measure used.

Background The impact of traumatic stress on autoimmune rheumatic diseases (ARDs) has been largely overlooked in existing research. This scoping review aimed to systematically examine the research literature relating to the relationship between traumatic stress and ARDs, by identifying study designs, methodologies, and gaps in the current research landscape. Methods The following databases and search interfaces were searched on 15th December 2023: Embase (via Embase.com), Medline (via PubMed), and Web of Science. Additional references were identified via bibliographies of included studies. The following studies were included, with no publication date limit and language restricted to English: targeting the association between traumatic stress and ARDs, observational methodologies, including cohort, case-control, and cross-sectional studies, exclusively focusing on self-reported psychological trauma impacts, such as adverse childhood experiences (ACEs), Post-traumatic Stress Disorder (PTSD), or major life stressors. Two authors independently assessed the studies for inclusion criteria and extracted the data. Results This scoping review revealed connections between traumatic stress and ARDs through an analysis of 21 included studies, highlighting the scarcity of research in this area. The studies, primarily from high-income countries and especially the USA, span from 2000 to 2023, indicating a growing interest in recent years and employing a range of methodologies. Traumas such as ACEs, PTSD, and major life events were frequently examined, showing a strong association with an increased risk and severity of ARDs, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Conclusion This scoping review reveals a notable dearth in research on the impact of traumatic stress, such as ACEs, PTSD, and major life events, on ARDs, especially on rare diseases, yet underscores a significant association between trauma and ARD severity or incidence. It highlights the critical need for future investigations to broaden the scope of ARDs studied, extend research to less represented regions, and utilize diverse, standardized methodologies to deepen our understanding of the trauma-ARD association.

Background Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. Aims This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ − 2.5 and a recent fracture). Methods A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). Results From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. Discussion Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. Conclusions Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

The presented guidelines are an update of the position paper, endorsed by the International Osteoporosis Foundation (IOF), on nomenclature of bone markers published over 2 decades ago. Novel insight into bone biology and pathophysiology of bone disorders has highlighted the increasing relevance of new and known mediators implicated in various aspects of bone metabolism. This updated guideline proposes the nomenclature Bone Status Indices (BSI) as the comprehensive classification rather than bone turnover markers, bone markers, metabolic markers of bone turnover or metabolic markers of bone turnover, that are currently in use for the implicated molecules. On behalf of the IFCC Committee on Bone Metabolism and the Joint IOF Working Group and IFCC Committee on Bone Metabolism, the authors propose standardized nomenclature, abbreviations and measurement units for the bone status indices.

This study aims to understand how osteoporosis medication acceptance varies across countries with differing guidance on treatment threshold and influence of clinical and demographic factors. A total of 79.2

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles. To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95

Task Force on ‘Clinical Algorithms for Fracture Risk’ commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

BackgroundThis study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT-P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes.Research design and methodsThis double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT-P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated.ResultsOf 154 participants randomized (76 CT-P41; 78 US-denosumab), 151 received study drug (74 CT-P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3).ConclusionsFollowing a single dose in healthy males, CT-P41 demonstrated PK equivalence with US-denosumab.Trial registrationClinicalTrials.gov: NCT06037395