Current Osteoporosis Reports最新文献

Purpose of review: This review summarizes the recently published scientific evidence regarding the role of enzymes engaged in de novo anabolic biosynthesis, catabolic, and salvage pathways of ceramide bioactive sphingolipids in bone dynamics and skeletal health.

Recent findings: Ceramides are precursors for bioactive sphingolipids, including sphingosine, sphingosine-1-phosphate, and others. Studies of bone metabolism and bone-related cells demonstrated that ceramide and sphingosine-1-phosphate control levels of bone remodeling and resorption generated by osteoblasts and osteoclasts. Multiple published studies demonstrated the critical role of enzymes in regulating the ceramide/sphingosine-1-phosphate ratio relative to bone physiology and the promotion of inflammatory osteolysis. Accordingly, emerging evidence suggests that targeting sphingolipid metabolism has the potential to alleviate inflammatory osteolysis and accelerate bone regeneration. Therefore, this study aimed to discuss current knowledge about crosstalk between sphingolipids and their metabolic enzymes within osteoclast and osteoblast coupling in bone remodeling and pathogenic osteolysis. This review highlights the complexity of de novo sphingolipid biosynthesis and knowledge gaps in bone physiology and pathology. We also discuss the importance of canonical and non-canonical mammalian and bacterial-derived sphingolipids relative to bone health.

Purpose of review: This review summarises the latest evidence on effects of exercise on falls prevention, bone mineral density (BMD) and fragility fracture risk in postmenopausal women, explores hypotheses underpinning exercise-mediated effects on BMD and sheds light on innovative concepts to better understand and harness the skeletal benefits of exercise.

Recent findings: Multimodal exercise programs incorporating challenging balance exercises can prevent falls. Emerging clinical trial evidence indicates supervised progressive high-intensity resistance and impact training (HiRIT) is efficacious in increasing lumbar spine BMD and is safe and well-tolerated in postmenopausal women with osteoporosis/osteopenia. There remains uncertainty regarding durability of this load-induced osteogenic response and safety in patients with recent fractures. Muscle-derived myokines and small circulating extracellular vesicles have emerged as potential sources of exercise-induced muscle-bone crosstalk but require validation in postmenopausal women. Exercise has the potential for multi-modal skeletal benefits with i) HiRIT to build bone, and ii) challenging balance exercises to prevent falls, and ultimately fractures. The therapeutic effect of such exercise in combination with osteoporosis pharmacotherapy should be considered in future trials.

Purpose of review: Osteoporosis (OP) is characterized by degraded bone microstructure, loss of bone mass and increased risk of fragility fractures. Currently, T-score determined by dual-energy X-ray absorptiometry (DEXA) measurements has been regarded as the gold standard for the diagnosis of osteoporosis. However, multiple factors have indicated that the T-score is insufficient to identify individuals with osteoporosis at a potentially high risk of fracture, or accurately detect those who require treatment, or continuously monitor the risk of re-fracture and clinical outcomes after treatment. This review covers publications in a range of ten years and comprehensively summarizes the studies in laboratory-based biomarkers for osteoporotic fractures (OF), aiming to provide physicians and surgeons with an update of clinical research in identification, verification and application of these tools, and to provide useful information for the design of future clinical studies.

Recent findings: It was found that bone formation markers (such as PINP, BGP, ECM1 and SOST), bone resorption markers (such as β-CTX, TRAcP5b, osteocalcin, RANKL, RANKL/OPG ratio, and t-PINP/β-CTX), hormonal biomarkers (such as IGF- 1, PTH, leptin, adiponectin and AMH), indicators of inflammation and oxidative stress (SII, IL- 6, LTL, FlOP_360, FlOP_400, and GGT), microRNAs (such as miR- 21, miR- 320a- 3p, miR- 491 - 5p, miR- 485 - 3p, miR- 19b- 1- 5p, miR- 203a, miR- 31 - 5p, miR- 502 - 3p, miR- 4739, miR- 497, miR- 19b, and miR- 107), other biomarkers (SAF-AGEs and glycine), adipocytokines (irisin and Omentin- 1), senescence biomarkers (RDW), and lncRNAs (MIAT) may be useful biomarkers for clinical practice. Further validation of these biomarkers and a better understanding of the underlying molecular mechanisms may help in the development and application of these biomarkers for risk prediction of OF, differential diagnosis among OP, OF and healthy individuals, as well as post-operative monitoring of re-fracture risk and treatment outcomes.

Purpose of review: Osteoporosis is a prevalent skeletal disorder in postmenopausal women and older adults. Kefir has gained attention for its potent antioxidative, anti-inflammatory, and immunomodulatory properties. This review consolidates findings on kefir-derived peptides' interventions in osteoporosis models and evaluates the therapeutic potential of kefir components in preventing osteoporosis, thereby enhancing its application in clinical nutrition strategies for osteoporosis management.

Recent findings: Kefir-derived peptides exhibit osteoprotective potential in various animal models of osteoporosis, in which several antioxidative and ACE-inhibitory peptides have been shown to promote osteoblast differentiation and mineralization. In addition, emerging evidence supports the role of kefir-derived probiotics and exopolysaccharides (kefiran) in mitigating bone loss. Kefir holds significant promise in the management of osteoporosis due to its unique composition of bioactive components promoting bone health. While research is still in its early stages, evidence suggests kefir's potential as a natural approach to osteoporosis prevention and management.

Purpose of the review: Eosinophils are traditionally known for their role in immune defense against parasites and their involvement in various immunopathologies, including eosinophilic airway diseases, eosinophilic dermatoses, and gastrointestinal disorders. However, recent findings from our group and other leading laboratories have broadened this perspective, revealing that eosinophils also play crucial roles in tissue development, homeostasis, and regeneration. This review aims to highlight the regulatory functions of eosinophils within the bone niche and emphasize the importance of further research into their role in bone biology.

Recent findings: Growing evidence suggests that eosinophils are key regulators of bone metabolism, extending beyond their established roles in immunity and inflammation. They contribute to bone homeostasis by inhibiting osteoclast differentiation, helping to prevent excessive bone resorption in osteoporosis and inflammatory arthritis. Additionally, eosinophils may promote osteoblast-mediated bone formation, modulate the mesenchymal and hematopoietic stem cell niche, and contribute to the bone microenvironment by affecting vascularization and extracellular matrix composition. However, their impact may vary under pathological conditions. Patients with eosinophilic disorders are often at an increased risk of osteoporosis and fragility fractures, though this is largely attributed to disease-related treatments rather than eosinophil activity itself. Despite emerging insights into the role of eosinophils in bone biology, the underlying mechanisms remain incompletely understood. Further research is essential to elucidate how eosinophils influence bone physiology and pathology.

Purpose of review: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a complex condition impacting patients with kidney failure and characterized by inter-related features such as hyperparathyroidism, hyperphosphatemia, and hypocalcemia. Current treatments include active vitamin D sterols, calcimimetics, and phosphate binders alone and in combination. However, identifying optimal treatment is challenged by interdependency among CKD-MBD features, requiring new approaches to understand dynamic systems. In this review, we discuss challenges and opportunities for a more integrated view of CKD-MBD care.

Recent findings: Few clinical studies in CKD-MBD care have incorporated a dynamic understanding of the disorder and its treatment. Dynamic treatment regime methods are an evolving area of artificial intelligence (AI) that offer a promising approach for modeling and understanding CKD-MBD care. Efforts to date have included dynamic systems and quantitative systems pharmacology-based models to simulate the impact of alternative treatment regimes. Additional studies utilizing dynamic treatment regime approaches may help improve knowledge gaps in CKD-MBD care. Although preliminary research highlights the potential of dynamic treatment regime approaches in optimizing CKD-MBD management, further investigation and clinical validation are necessary to fully harness this approach for improving patient outcomes.

Purpose of the review: Osteoporosis requires life-long management. This involves the use of different drugs in various sequences followed by long-term maintenance therapy. This review highlights the important transitions among osteoporosis therapies and outlines a strategy of intermittent bisphosphonate therapy for long-term maintenance.

Recent findings: Over the past few years, the effects and limitations of long-term treatment with bisphosphonates and denosumab have become apparent as have several key factors in the sequential use of anti-remodeling drugs and osteoanabolic agents. Strategies for transitions from estrogen, bisphosphonates, denosumab and the bone-forming drugs will be discussed, based on extant evidence, clinical experience and expert opinion. By appropriate selection of both the initial and subsequent drugs for the prevention and treatment of osteoporosis, therapeutic benefits can be optimized and safety issues minimized. Developing a strategy for long-term maintenance of the benefits of the initial therapies can provide a life plan for managing patients with osteoporosis.

Purpose: Hypophosphatasia (HPP) is a rare, dento-osseous disorder caused by impaired activity of tissue non-specific alkaline phosphatase (TNSALP), a key enzyme in tissue mineralization. This review provides a clinical perspective on the current medical treatment of both children and adults with HPP.

Recent findings: Dental problems, rickets in children, and osteomalacia in adults are common in HPP. However, disease manifestations in individual patients are exceptionally variable. Recent studies broadened our understanding of HPP symptoms. For example, data showed behavioral health challenges in HPP children, and a large, real-world data set from the Global HPP Registry demonstrated that HPP adults regardless of the time of disease onset exhibit significant disease burden and are broadly affected by non-skeletal impairments, such as pain and chronic fatigue. Treatment for HPP relies on the enzyme replacement asfotase alfa. Small, mostly pediatric trials initially established dosing, safety and efficacy of asfotase alfa, and latest data corroborated the long-term safety and efficacy in both children and pediatric-onset adults. Data from several recent observational studies, including the Global HPP Registry, underscored that asfotase alfa improves physical functions, non-skeletal symptoms such as pain, and quality-of-life (QoL) in adults irrespective of age-of-onset. Clinical use of asfotase alfa is based on prescribing information and evidence-based consensus guidelines. However, recommendations for initiation of therapy are just emerging. Alternatives to asfotase alfa remain limited, but a derivative, efzimfotase alfa, currently undergoes clinical testing. Studies in larger HPP patient populations suggest efficacy of enzyme replacement therapy independent of patient age and time of disease onset.

Purpose of review: The purpose of this review is to describe the approach to osteoporosis management in men in the setting of limited evidence.

Recent findings: Although men have less fractures than women, men have greater mortality after fractures as well as increased complications, including infection and major cardiovascular events. Unfortunately, men are not routinely screened for osteoporosis, partially due to limited insurance coverage in the United States. Due to screening barriers and lack of robust evidence of fracture reduction with therapeutic agents in men, treatment rates have also been low. A 2022 network meta-analysis of osteoporosis treatment in men found that with all the randomized controlled trials performed in men, there was only sufficient power to show vertebral fracture reduction. A large case-control observational study from 2024 did find that osteoporosis treatment reduced odds of hip fracture similarly in men and women. Men have fractures, with greater morbidity and mortality than women. Although osteoporosis research is lacking in men, providers should assess fracture risk in men and allow them the opportunity to reduce their fracture risk.

Purpose of review: to describe and compare the efficacy and safety of the main PTH treatments, namely PTH(1-84) and palopegteriparatide, for the management of hypoparathyroidism.

Recent findings: neither PTH (1-84) nor PTH(1-34) have been shown a clear and consistent favorable impact on the 24 h urinary calcium excretion normalization, while the positive effect on quality of life is still debated. Recently, the Food & Drug Administration and the European Medicines Agency approved palopegteriparatide as the first true replacement therapy for hypoPT management. Palopegteriparatide is a prodrug of PTH(1-34), administered once daily, and designed to provide continuous exposure to released PTH over a 24-h dosing period. According to phase II and phase III studies, palopegteriparatide seems to fill the gaps identified in existing therapies for hypoPT. Palopegteriparatide is the first real replacement therapy for the management of hypoparathyroidism and seems to fill the gaps identified in existing therapies for hypoPT.