Current Osteoporosis Reports最新文献

Purpose of review: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models.

Recent findings: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Purpose of review: To provide a comprehensive overview of the inflammatory response following anterior cruciate ligament (ACL) injury and to highlight the relationship between specialized pro-resolving mediators (SPMs) and inflammatory joint conditions, emphasizing the therapeutic potential of modulating the post-injury resolution of inflammation to prevent posttraumatic osteoarthritis (PTOA).

Recent findings: The inflammatory response triggered after joint injuries such as ACL tear plays a critical role in posttraumatic osteoarthritis development. Inflammation is a necessary process for tissue healing, but unresolved or overactivated inflammation can lead to chronic diseases. SPMs, a family of lipid molecules derived from essential fatty acids, have emerged as active players in the resolution of inflammation and tissue repair. While their role in other inflammatory conditions has been studied, their relationship with PTOA remains underexplored. Proinflammatory mediators contribute to cartilage degradation and PTOA pathogenesis, while anti-inflammatory and pro-resolving mediators may have chondroprotective effects. Therapies aimed at suppressing inflammation in PTOA have limitations, as inflammation is crucial for tissue healing. SPMs offer a pro-resolving response without causing immunosuppression, making them a promising therapeutic option. The known onset date of PTOA makes it amenable to early interventions, and activating pro-resolving pathways may provide new possibilities for preventing PTOA progression. Harnessing the pro-resolving potential of SPMs may hold promise for preventing PTOA and restoring tissue homeostasis and function after joint injuries.

Purpose of review: The purpose of this review is to discuss the role of macrophages in the regulation of skeletal health with age, particularly in regard to both established and unexplored mechanisms in driving inflammation and senescence.

Recent findings: A multitude of research has uncovered mechanisms of intrinsic aging in macrophages, detrimental factors released by these immune cells, and crosstalk from senescent mesenchymal cell types, which altogether drive age-related bone loss. Furthermore, bone marrow macrophages were recently proposed to be responsible for the megakaryocytic shift during aging and overall maintenance of the hematopoietic niche. Studies on extra-skeletal macrophages have shed light on possible conserved mechanisms within bone and highlight the importance of these cells in systemic aging. Macrophages are a critically important cell type in maintaining skeletal homeostasis with age. New discoveries in this area are of utmost importance in fully understanding the pathogenesis of osteoporosis in aged individuals.

Purpose of review: The purpose of this review is to provide a background on osteocytes and the primary cilium, discussing the role it plays in osteocyte mechanosensing.

Recent findings: Osteocytes are thought to be the primary mechanosensing cells in bone tissue, regulating bone adaptation in response to exercise, with the primary cilium suggested to be a key mechanosensing mechanism in bone. More recent work has suggested that, rather than being direct mechanosensors themselves, primary cilia in bone may instead form a key chemo-signalling nexus for processing mechanoregulated signalling pathways. Recent evidence suggests that pharmacologically induced lengthening of the primary cilium in osteocytes may potentiate greater mechanotransduction, rather than greater mechanosensing. While more research is required to delineate the specific osteocyte mechanobiological molecular mechanisms governed by the primary cilium, it is clear from the literature that the primary cilium has significant potential as a therapeutic target to treat mechanoregulated bone diseases, such as osteoporosis.

Purpose of review: This review examines the diverse functional relationships that exist between the peripheral nervous system (PNS) and bone, including key advances over the past century that inform our efforts to translate these discoveries for skeletal repair.

Recent findings: The innervation of the bone during development, homeostasis, and regeneration is highly patterned. Consistent with this, there have been nearly 100 studies over the past century that have used denervation approaches to isolate the effects of the different branches of the PNS on the bone. Overall, a common theme of balance emerges whereby an orchestration of both local and systemic neural functions must align to promote optimal skeletal repair while limiting negative consequences such as pain. An improved understanding of the functional bidirectional pathways linking the PNS and bone has important implications for skeletal development and regeneration. Clinical advances over the next century will necessitate a rigorous identification of the mechanisms underlying these effects that is cautious not to oversimplify the in vivo condition in diverse states of health and disease.

Purpose of review: The purpose of this review is to synthesize the recently published scientific evidence on disparities in epidemiology and management of fragility hip fractures.

Recent findings: There have been a number of investigations focusing on the presence of disparities in the epidemiology and management of fragility hip fractures. Race-, sex-, geographic-, socioeconomic-, and comorbidity-based disparities have been the primary focus of these investigations. Comparatively fewer studies have focused on why these disparities may exist and interventions to reduce disparities. There are widespread and profound disparities in the epidemiology and management of fragility hip fractures. More studies are needed to understand why these disparities exist and how they can be addressed.

Purpose of review: The role of wnt signalling in atherogenesis raises the possibility that the wnt inhibitor, sclerostin, provides a natural defence to this process, and that anti-sclerostin antibodies might increase the risk of atherosclerosis and associated conditions such as CVD. This article aims to triangulate evidence concerning possible adverse effects of sclerostin inhibition on CVD risk.

Recent findings: Randomised controlled trials of treatment with the anti-sclerostin antibody, romosozumab, have yielded conflicting evidence with respect to possible adverse effects of sclerostin inhibition on CVD risk. To further examine the causal relationship between sclerostin inhibition and CVD risk, three Mendelian randomisation (MR) studies have examined effects of sclerostin lowering on CVD outcomes, using common genetic variants in the SOST gene which produces sclerostin, to mimic effects of a randomised trial. Concordant findings were seen in two studies, comprising an effect of sclerostin lowering on increased risk of MI and type II diabetes mellitus. One study also suggested that sclerostin lowering increases coronary artery calcification. Triangulation of evidence from different sources provides some suggestion that sclerostin lowering increases MI risk, supporting the need for CVD risk assessment when considering treatment with romosozumab.

Purpose of review: To summarize the recently published scientific evidence on fracture risk in hypoparathyroidism.

Recent findings: Hypoparathyroidism is characterized by a low bone turnover and a high bone mineral density. Data on fracture risk are sparse and due to the rarity of the disease, available studies have only been able to include relatively few patients. Risk of non-vertebral fractures does not seem to be affected to any major degree, although epidemiological studies suggest a decreased risk of fractures at the humerus in postsurgical hypoparathyroidism, whereas an increased risk of fractures at the upper arm has been shown in non-surgical hypoparathyroidism. Several, but not all, studies have also pointed towards an increased risk of vertebral fractures, especially in non-surgical hypoparathyroidism. Fractures at the appendicular skeleton do not seem to be of specific concern in hypoparathyroidism, but emerging data suggest an increased risk of vertebral fractures, which needs to be clarified further in upcoming studies.

Purpose of review: This review summarizes the current knowledge regarding osteoporosis and fracture among older US Asian adults.

Recent findings: Asian adults have lower (areal) bone density than non-Hispanic White adults and thus are more likely to be diagnosed and treated for osteoporosis, despite their lower risk of hip fracture. The latter may relate to favorable characteristics in hip geometry, volumetric bone density, and bone microarchitecture; lower risk of falls; and other clinical factors. The fracture risk calculator FRAX accounts for the lower risk of hip fracture among US Asian adults. However, data on major osteoporotic fracture risk remain limited. Fracture rates also vary by Asian subgroup, which may have implications for fracture risk assessment. Furthermore, among women receiving bisphosphonate drugs, Asian race is a risk factor for atypical femur fracture, an uncommon complication associated with treatment duration. Recent clinical trial efficacy data pertaining to lower bisphosphonate doses and longer dosing intervals may be relevant for Asian adults. More research is needed to inform osteoporosis care of US Asian adults, including risk-benefit considerations and the optimal duration of bisphosphonate treatment. Greater evidence-based guidance for primary fracture prevention among US Asian adults will ensure health equity in the prevention of osteoporotic fractures.

Purpose of review: Recent advancements in "omics" technologies and bioinformatics have afforded researchers new tools to study bone biology in an unbiased and holistic way. The purpose of this review is to highlight recent studies integrating multi-omics data gathered from multiple molecular layers (i.e.; trans-omics) to reveal new molecular mechanisms that regulate bone biology and underpin skeletal diseases.

Recent findings: Bone biologists have traditionally relied on single-omics technologies (genomics, transcriptomics, proteomics, and metabolomics) to profile measureable differences (both qualitative and quantitative) of individual molecular layers for biological discovery and to investigate mechanisms of disease. Recently, literature has grown on the implementation of integrative multi-omics to study bone biology, which combines computational and informatics support to connect multiple layers of data derived from individual "omic" platforms. This emerging discipline termed "trans-omics" has enabled bone biologists to identify and construct detailed molecular networks, unveiling new pathways and unexpected interactions that have advanced our mechanistic understanding of bone biology and disease. While the era of trans-omics is poised to revolutionize our capacity to answer more complex and diverse questions pertinent to bone pathobiology, it also brings new challenges that are inherent when trying to connect "Big Data" sets. A concerted effort between bone biologists and interdisciplinary scientists will undoubtedly be needed to extract physiologically and clinically meaningful data from bone trans-omics in order to advance its implementation in the field.