Current Osteoporosis Reports最新文献

Purpose of review: Intravital imaging technologies have significantly transformed our understanding of osteocyte biology by enabling real-time visualization of these cells within their native microenvironment. Historically viewed as static, embedded cells, osteocytes are now recognized as dynamic and responsive, actively participating in bone remodeling, mechanotransduction, and intercellular communication. This review highlights recent advances in intravital microscopy techniques-including two-photon and three-photon imaging-and their application to studying osteocyte function in situ and in vivo.

Recent findings: Innovations in intravital imaging have allowed researchers to visualize osteocyte structural plasticity, intracellular signaling dynamics, and cell-cell interactions within the dense, mineralized bone matrix. These approaches have provided new insights into osteocyte mechanosensitivity and functional heterogeneity. However, challenges remain, including optical scattering in cortical bone and the technical complexity required for imaging preparation and data acquisition. The continued refinement of intravital imaging methods will further enhance our ability to investigate key questions regarding osteocyte network connectivity, mechanotransduction, and plasticity over extended timescales. Advances in imaging technology hold great promise to bridge the experimental flexibility of in vitro systems with the physiological complexity of living bone, opening new avenues for discovery in musculoskeletal biology.

Purpose of review: Sex specific differences in the determinants, occurrence, and distribution of osteoporosis and osteoporotic fractures play a pivotal role in the implementation of timely surveillance, prevention and effective treatment approaches. This review is aimed at synthesizing recently published scientific evidence on disparities in the epidemiology and management of osteoporosis and related fragility fractures in men.

Recent findings: Several studies have identified race-, sex-, geographic-, socioeconomic-, and comorbidity-based disparities in osteoporosis care. Over the last decade, the awareness and imperative for identifying osteoporosis in men have increased. Nonetheless, the treatment gap is increasing and osteoporosis in men remains severely underappreciated and undertreated. Fewer studies in men have focused on the factors beyond osteoporosis awareness. Recent data of individuals aged 50 years and older show an alarmingly greater increase in hip fractures in men compared to women. This coupled with the existing knowledge of greater disability burden and excess mortality due to fragility fractures in men is a cause of public health concern. This review offers a comprehensive examination of widespread and profound disparities across the spectrum of osteoporosis care and post-fracture management in men and highlights the considerable health economic aspect of this burden. We call for targeted multifaceted interventions: develop novel methods to engage patients and health professionals, increase screening and treatment of osteoporosis in men, conduct epidemiological studies focused on disease phenotyping and risk factor assessment, studies on the identification of perceptions and barriers to effective screening and treatment, expansion and further evaluation of cost-effective therapies and primary prevention strategies for fractures, implementation of fracture liaison services to address the treatment gap in secondary prevention, and promote inclusivity in outcome studies and therapeutic trials. These interventions are paramount to reduce inequities in osteoporosis care and post-fracture care in men.

Purpose of review: This review evaluates current management options for managing ankle fractures in geriatric patients with osteoporosis. It addresses the challenges posed by compromised bone integrity and examines operative and non-operative approaches to promote early mobility and functional recovery in elderly individuals.

Recent findings: Recent studies show that both surgical and non-surgical management can yield comparable functional outcomes, but complication profiles differ. Studies have assessed advanced fixation options such as standard and extended ORIF, hindfoot nailing, and fibular nailing, with growing interest in methods that accommodate poor bone quality and enable early weightbearing. Individualised care pathways and the need for standardisation in rehabilitation protocols are important. Personalised and multidisciplinary treatment is essential for this group of patients. No single intervention is optimal; treatment must consider patient frailty, comorbidities, and functional demands. Future research should focus on randomised controlled trials to refine surgical indications and rehabilitation strategies, improving outcomes and reducing complications.

Purpose: To synthesize evidence on the efficacy of osteoanabolic therapies (teriparatide, abaloparatide, romosozumab) in adults with type 2 diabetes mellitus (T2D), focusing on changes in bone mineral density (BMD) and fractures, and to explore whether responses differ between people with and without diabetes.

Findings: Following PRISMA guidelines, we searched PubMed/MEDLINE, Embase and Scopus databases till April 30, 2025 (PROSPERO: CRD420251044760). Five studies met criteria (n = 1,469 with T2D; n = 12,052 without diabetes): two post hoc analyses of randomized controlled trials (RCTs) (ACTIVE and ARCH trials) and three observational studies. Using random-effects model, osteoanabolic therapy in T2D increased lumbar spine BMD by a mean difference (MD) of 5.06% (95% CI: 1.62, 8.50; I²=93.3%). Sensitivity analysis restricted to RCTs demonstrated a larger, highly consistent effect at lumbar spine (MD 7.49%, 95% CI: 6.56, 8.41; I²=0%). Femoral neck BMD increased by 2.61% (95% CI: 1.84, 3.38; I²=0%). Evidence for fracture outcomes in T2D was limited to a single RCT (ACTIVE), in which non-vertebral fractures were reduced with abaloparatide versus placebo (p = 0.04), whereas new vertebral fractures were not different between groups. Two observational studies showed that in people with T2D, osteoanabolic agents improved BMD as much as, or more than, in non-diabetic individuals, while fracture rates were mostly similar between the groups. Osteoanabolic agents yield meaningful BMD gains in T2D, particularly at lumbar spine, with modest improvements at femoral neck. Limited fracture data suggest possible benefit but remain underpowered, underscoring the need for diabetes-specific RCTs with fracture endpoints.

Purpose of review: This review summarizes recent findings of the pathophysiology of bone fragility with a particular focus on type 2 diabetes (T2D). It proposes that T2D is a condition of accelerated aging, highlighting mechanisms related to aging as key contributors to bone fragility.

Recent findings: Multiple mechanisms have been proposed to explain the increased fracture risk in individuals with T2D; however, a unified model is still lacking. In this review, we propose that T2D represents a state of accelerated aging, with age-related processes, such as cellular senescence, stem cell exhaustion, enhanced autophagy, intercellular communication, dysbiosis, chronic inflammation, and epigenetic changes including microRNA expression, driving the development of diabetic bone fragility. These mechanisms predominantly impair bone cell function, ultimately compromising bone quality. The pathophysiology of bone fragility in T2D is discussed within the broader context of aging, emphasizing how fundamental biological mechanisms of the aging process contribute to diabetic bone disease.

Purpose of review: The periosteum has long been recognized as being essential for bone growth and repair. More recently, its involvement has been observed in a range of pathological conditions, including cancer progression and invasion, premature closure of the growth plate, bone pain, pseudarthrosis, and craniosynostosis. Given that the periosteal reaction often serves as an early indicator of skeletal abnormalities, the periosteum likely plays a pivotal role at the interface of bone health and disease. In this review, recent advances in our understanding of periosteal biology are highlighted.

Recent findings: Recent studies employing lineage tracing and genetic loss-of-function approaches have highlighted the critical role of periosteal stem cells and their progenies, as well as periosteum/perichondrium-derived factors, in both bone physiology and pathology. Crosstalk between the periosteum/perichondrium and the growth plate controls skeletal growth, and complex multicellular interactions in the periosteum underlies the pathogenesis of pseudarthrosis and craniosynostosis. The protective role of the periosteum against cancer progression has garnered attention, expanding our understanding of periosteum function. It is now evident that the periosteum is a crucial skeletal element that is key for maintaining vertebrate homeostasis. Future research into the cellular communication in the periosteum, as well as its interactions with other skeletal elements and extra-skeletal systems, will be key to develop novel therapeutic strategies for skeletal diseases.

Purpose of review: Osteoporosis and musculoskeletal diseases, including osteoarthritis and sarcopenia, contribute substantially to global morbidity and healthcare costs. This review explores how proteogenomics integrates genomic and proteomic data to refine disease classification, identify causal pathways, and accelerate biomarker and drug target discovery.

Recent findings: Large-scale proteomic studies, including UK Biobank-based research, have identified circulating proteins associated with musculoskeletal disease risk and progression. Proteomic risk models outperform conventional clinical metrics in predicting outcomes. Genomics, proteomics, and proteogenomics have facilitated the identification of causal markers through methods such as genome-wide association studies, effector gene mapping, and proteome-wide Mendelian randomization. Pathways implicated in disease mechanisms include extracellular matrix remodeling (e.g., COL6A3, COL9A1), metabolic regulation (e.g., IGFBP2, GDF15), inflammatory processes (e.g., TNF family ligands, CXCL17), and sex-hormone-related signaling (e.g., FSHB, SHBG). While these biological processes contribute across osteoporosis, osteoarthritis, and sarcopenia, distinct proteins have also been linked to disease-specific pathophysiology, offering potential therapeutic targets. Genomics, proteomics, and proteogenomics refine our understanding of musculoskeletal conditions and hold strong potential for improving early diagnosis, enhancing risk stratification, and advancing precision treatments.

Purpose of review: Hypophosphatasia (HPP) and type 1 diabetes (T1D) are both associated with low bone turnover and increased fracture risk. In this review, our objectives were to (a) discuss results of our pilot study aimed to evaluate prevalence and clinical and radiological characteristics of HPP in adults with T1D and (b) to review literature on the use of electronic medical records (EMR) for HPP case findings.

Recent findings: In our pilot study, 18 individuals had persistent low alkaline phosphatase levels (ALP) [18/1723, 1.05%]. Among 10 participants who completed the study with potential HPP and T1D, three had a pathogenic ALPL mutation (0.16% prevalence), and six had elevated serum vitamin B6. No significant differences were found in DXA-based bone density, QCT-based bone density, or Finite element-estimated bone strength between the potential HPP group, T1D adults, and controls. We did not find any study that evaluated persistent low ALP levels or potential HPP in patients with diabetes (either type 1 or type 2 diabetes). The literature reported higher prevalence of low ALP levels when electronic medical records were searched (~ 1-3%). However, prevalence of suspected HPP based on persistent low ALP levels and/or clinical signs and symptoms was around 0.5% or lower depending on sample size, methods and geographical locations. Our study suggests that EMR-based screening for HPP is feasible and may identify previously undiagnosed cases of HPP. Prevalence of potential HPP in T1D is around 1% and genetically confirmed HPP is 0.16% which is similar to reported prevalence of HPP in selected population without diabetes. Skeletal imaging and clinical presentations are not sufficient for identifying potential HPP in individuals with T1D. Given the increased fracture risk and low bone turnover typically seen in T1D, we propose that an EMR-based screening strategy could be a more effective approach for diagnosing HPP in T1D population.

Purpose of review: Osteoporosis is a systemic skeletal disease that presents unique challenges in spine surgery due to decreased bone mass, poor bone quality, and increased risk of fractures. This review aims to synthesize current understanding of osteoporosis in the context of spinal procedures, emphasizing the pathophysiology, diagnostic challenges, perioperative considerations, and evolving management strategies.

Recent findings: Despite high prevalence, osteoporosis remains underdiagnosed and undertreated in surgical candidates, with preoperative bone mineral density (BMD) screening often overlooked. Recent evidence underscores the importance of optimizing bone health preoperatively through pharmacologic therapies, which includes bisphosphonates, denosumab, and anabolic agents like teriparatide and romosozumab. Furthermore, surgical innovations such as cement augmentation and biomechanically optimized pedicle screw techniques are thoroughly discussed. New modalities, such as CT-based Hounsfield unit assessments and finite element analysis, offer improved preoperative evaluation of bone quality. Successful spine surgery outcomes in osteoporotic patients require a multidisciplinary approach that integrates early screening, targeted pharmacologic treatment, lifestyle modifications, and advanced surgical planning. Addressing osteoporosis comprehensively improves implant fixation, reduces complications like pseudoarthrosis and junctional failures, and enhances overall patient quality of life.