Current Osteoporosis Reports最新文献

Purpose of review: The purpose of this review is to summarize recently published scientific evidence (from January 1, 2020-January 1, 2025), on disparities in the diagnosis and treatment of osteoporosis and the treatment of fragility fractures in persons with cognitive impairment and dementia.

Recent findings: Worldwide, the population is aging, and coincident with this, the number of individuals with osteoporosis and dementia is rapidly increasing. Several reports have suggested a link between these two chronic conditions. Persons with dementia who sustain an osteoporotic fracture have excess morbidity and mortality compared to similarly aged populations without cognitive impairment. However, the extent to which these differences are a function of disparities in the diagnosis and treatment of osteoporosis and treatment and rehabilitation for osteoporotic fractures is not clear. In this summary, we review the evidence that health and health care disparities exist for older adults with cognitive impairment or dementia with respect to osteoporosis diagnosis and treatment and management of fragility fractures. We highlight unique considerations for persons with cognitive impairment or dementia relative to diagnosis of osteoporosis, choice and frequency of use of osteoporosis pharmacotherapies, and consideration for rehabilitation services post hip fracture. More research is necessary to determine how best to reduce health care disparities with respect to diagnosis and treatment of osteoporosis and fragility fractures in older adults with cognitive impairment or dementia. Considerations should include early identification of persons at risk for fracture, use of osteoporosis drug therapies that require less frequent dosing and are administered by clinicians to enhance adherence, and access to patient and family-centered rehabilitation post hip fracture.

Purpose of review: Arthroplasty (e.g., TKA, UKA, THA) is a gold-standard treatment for end-stage joint diseases, yet it often leads to periprosthetic bone mineral density (BMD) loss, increasing risks of implant loosening and fractures. This review aims to (1) evaluate current methods for measuring periprosthetic BMD, (2) analyze factors contributing to BMD reduction, and (3) discuss pharmacological interventions to mitigate bone loss, thereby improving postoperative outcomes.

Recent findings: Recent studies highlight three primary BMD assessment tools: DEXA (widely used but limited by artifact interference), QCT (3D precision but higher cost/radiation), and HRpQCT (high-resolution yet restricted to peripheral sites). Key contributors to BMD loss include stress shielding, surgical technique, patient-specific factors (e.g., age, osteoporosis), and postoperative management gaps. Pharmacological agents like teriparatide (anabolic), denosumab (anti-resorptive), and TCM (e.g., Epimedium-derived compounds) show efficacy in preserving periprosthetic BMD. Periprosthetic BMD loss remains a critical challenge post-arthroplasty. While current monitoring tools and pharmacological strategies offer promising solutions, limitations in accessibility and standardization persist. Future research should focus on personalized BMD management protocols, cost-effective monitoring technologies, and long-term outcomes of combined therapies to optimize implant longevity and patient quality of life.

Purpose of review: This review provides a background on osteoporosis, describes the relationship between osteoporosis and periprosthetic fracture following total hip arthroplasty (THA), as well as to discusses current management strategies and future directions for improved patient outcomes.

Recent findings: Periprosthetic fracture of the hip is among one of the most common reasons for revision following THA and occurs in 0.1-3.5% of individuals. Periprosthetic fractures come with significant cost, morbidity, and future mortality. Risks for periprosthetic fractures following THA include female sex, older age, rheumatoid arthritis, and osteoporosis. Recent works have demonstrated that osteoporosis plays an important role in the rising prevalence of periprosthetic fractures following THA. This review characterizes the interplay between osteoporosis and periprosthetic hip fractures following THA with emphasis placed upon the pathophysiology of osteoporosis, the mechanisms by which osteoporosis promote periprosthetic fractures, management of such fractures, and the potential for future therapies.

Purpose of the review: The purpose of this review article is to discuss how oxygen sensing mechanisms regulate the expression of key osteocyte markers such as podoplanin (E11), sclerostin (SOST), receptor activator of nuclear factor-κB ligand (RANKL), and fibroblast growth factor 23 (FGF23); summarize the relevance of targeting oxygen sensing pathways in osteocytes to improve bone health; and highlight the importance of osteocyte oxygen sensing mechanisms in maintaining good bone health during aging.

Recent findings: Oxygen sensing in osteocytes regulates osteocyte dendrites formation, bone mass and mineral metabolism through the regulation of E11, SOST, RANKL, and FGF23. Hypoxia Induced Factor (HIF) stabilization in osteocytes increases the activity of the histone deacetylase SIRT1 which represses SOST expression and increases the expression of FGF23. These recent findings suggest that targeting oxygen-associated pathways can be leveraged to control osteo-anabolic response and mineral metabolism. Aging is associated with the increase of circulating SOST; therefore, the mechanisms associated with SOST overproduction in bone may be linked to age-related changes in oxygen sensing in osteocytes. Understanding the changes of oxygen sensing mechanisms in osteocytes during aging may offer a therapeutic avenue to control SOST overproduction, a negative regulator of bone formation and therefore prevent age-related bone loss. We discuss how oxygen-sensing controls osteocyte physiology and how aging-mediated dysregulation of oxygen bioavailability promotes osteoporosis. We also explore how oxygen-modulating therapies can be used to improve bone healthspan.

Purpose of review: In this review, we summarize our evolving understanding of the epigenetic mechanisms directing the osteogenic differentiation of skeletal progenitor cells.

Recent findings: Advances in genome-wide approaches used to profile chromatin accessibility and histone modifications in skeletal progenitors have uncovered chromatin remodeling associated with progression of osteoblast differentiation and the key regulatory nodes driving this process. Utilization of cell culture systems and genetic mouse models highlight the key enzymes regulating histone posttranslational modifications and DNA methylation that promote the transition of cells from progenitor to mature osteoblast stage. Herein, the described studies provide emerging insights gained from pharmacologic targeting of chromatin modifiers promoting osteogenic differentiation of skeletal progenitors. While our fundamental understanding of chromatin modifiers and factors regulating chromatin accessibility and transcriptional activity in skeletal progenitors continues to develop, future research may inform new therapeutic approaches to promote osteoblast differentiation and enhance mineralization to augment fracture repair.

Purpose of review: To discuss current evidence on the diagnosis and management of osteoporosis in patients with chronic kidney disease (CKD).

Recent findings: Osteoporosis and fractures are prevalent in older CKD patients and associated with poor process indicators and outcomes. While osteoporosis treatment is generally similar in patients without or with CKD up to stage 3, there is still a lack of evidence to guide many areas of osteoporosis management in CKD stages 4-5. There is an urgent need to establish local multidisciplinary care pathways for CKD and dialysis patients with osteoporosis, involving nephrologists, bone specialists and fracture liaison services. Optimization of calcium and vitamin D metabolism and non-pharmacological measures including exercise and falls prevention should be considered in all patients. Withholding bone drugs solely based on glomerular filtration rates may constitute renalism (discrimination based on kidney function), which would further widen the already large treatment gap in osteoporosis. On the other hand, more evidence is needed to inform almost every aspect of anti-osteoporotic pharmacotherapy in CKD stages 4-5. The concept of choosing between antiresorptive or anabolic bone drugs based on a pre-treatment assessment of bone turnover (using biomarkers or bone biopsies), is a dogma in urgent need of critical re-evaluation. This narrative review aims to summarize our current understanding of the management of CKD-associated osteoporosis and fracture prevention in stage 4-5 CKD patients.

Purpose of review: Genome-wide association studies (GWAS) have significantly advanced osteoporosis research by identifying genetic loci associated with bone mineral density (BMD) and fracture risk. However, disparities persist due to the underrepresentation of non-European populations, limiting the applicability of polygenic risk scores (PRS). This review examines recent advancements in osteoporosis genetics, highlights existing disparities, and explores strategies for more inclusive research.

Recent findings: European-focused GWAS have identified key loci for osteoporosis, including WNT signaling (SOST, LRP5) and RUNX2 transcriptional regulation. However, fewer than 40% of these variants can be replicated in Asian and African populations. Emerging studies in non-European groups reveal population-specific loci, sex-specific associations, and gene-environment interactions. Advances in machine learning (ML)-assisted GWAS and multi-omics integration are improving genetic discovery. Expanding GWAS in diverse populations, integrating multi-omics data, refining ML-based risk models, and standardizing biobank data are essential for equitable osteoporosis research. Future efforts must prioritize clinical translation to enhance personalized osteoporosis prevention and treatment.

Purpose of review: This review explores the role of cell communication network (CCN) proteins in regulating skeletal physiology, aging, and disease, particularly within the context of balanced bone remodeling.

Recent findings: Recent conceptualization of paracrine and endocrine networks in bone marrow as a form of osteoimmunological crosstalk suggests a significant role for matricellular signaling in regulating bone homeostasis. As multifunctional adapters of cell-matrix interactions, CCNs are emerging as a focal point for parathyroid hormone (PTH) signaling and regulation of the RANKL/RANK/OPG axis in skeletal aging. Altered bone marrow CCN expression creates a permissive environment for accelerated postmenopausal bone loss and may contribute to the pathogenesis of osteoporosis and other diseases related to skeletal aging. CCNs modulate fundamental signaling mechanisms in bone development, homeostasis and repair. During aging, dysregulation of CCNs may negatively affect skeletal health and contribute to disease progression. As a result, CCNs may constitute promising therapeutic targets for improving and maintaining aging bone health.

Purpose of review: Mechanical loading of bone is an important physical stimulus for bone tissue remodeling and adaptation. It is transmitted from the extracellular matrix all the way to the osteocyte nucleus via the extracellular matrix-integrin-cytoskeleton-nucleus system. Mitochondria are integral in sensing of mechanical loads to allow the cell to adapt to its environment. This review provides a background of mitochondrial distribution in osteocytes especially during mechanical loading, discussing the importance of mitochondrial distribution in osteocyte mechanosensitivity and mechanotransduction.

Recent findings: Mitochondria throughout the osteocyte are highly dynamic and provide essential metabolic and signal functions to regulate osteocyte morphology and function. They undergo the processes of fission and fusion accompanied by mitochondrial DNA distribution. The mitochondrial network structure and function in osteocytes can be regulated by mechanical loading. Interestingly, mitochondria can be transmitted by osteocytes into adjacent cells to communicate with them via tunneling nanotubes, migrasomes, and blebbisomes, causing changes in cell morphology and/or function. Mitochondrial distribution in or out osteocytes can be rearranged by physical and (bio)chemical signals via fission and fusion, as well as tunneling nanotubes, migrasomes, and blebbisomes. Mechanical loading-induced changes in mitochondria may drive signaling pathways of cell function in aging and diseases. More insights into interactions between neighbouring osteocytes and between osteocytes and other cell types would facilitate the development of new strategies to apply mitochondrial therapy for bone-related diseases.