Current Osteoporosis Reports最新文献

Purpose of review: Recently, there has been an increasing number of studies on the crosstalk between the bone and the bone marrow and how it pertains to anemia. Here, we discuss four heritable clinical syndromes contrasting those in which anemia affects bone growth and development, with those in which abnormal bone development results in anemia, highlighting the multifaceted interactions between skeletal development and hematopoiesis.

Recent findings: Anemia results from both inherited and acquired disorders caused by either impaired production or premature destruction of red blood cells or blood loss. The downstream effects on bone development and growth in patients with anemia often constitute an important part of their clinical condition. We will discuss the interdependence of abnormal bone development and growth and hematopoietic abnormalities, with a focus on the erythroid lineage. To illustrate those points, we selected four heritable anemias that arise from either defective hematopoiesis impacting the skeletal system (the hemoglobinopathies β-thalassemia and sickle cell disease) versus defective osteogenesis resulting in impaired hematopoiesis (osteopetrosis). Finally, we will discuss recent findings in Diamond Blackfan anemia, an intrinsic disorder of both the erythron and the bone. By focusing on four representative hereditary hematopoietic disorders, this complex relationship between bone and blood should lead to new areas of research in the field.

Purpose of review: The study aims to provide updated information on the genetic factors associated with the diagnoses 'Diffuse Idiopathic Skeletal Hyperostosis' (DISH), 'Ossification of the Posterior Longitudinal Ligament' (OPLL), and in patients with spinal ligament ossification.

Recent findings: Recent studies have advanced our knowledge of genetic factors associated with DISH, OPLL, and other spinal ossification (ossification of the anterior longitudinal ligament [OALL] and the yellow ligament [OYL]). Several case studies of individuals afflicted with monogenic disorders, such as X-linked hypophosphatemia (XLH), demonstrate the strong association of fibroblast growth factor 23-related hypophosphatemia with OPLL, suggesting that pathogenic variants in PHEX, ENPP1, and DMP1 are associated with FGF23-phosphate wasting phenotype and strong genetic factors placing patients at risk for OPLL. Moreover, emerging evidence demonstrates that heterozygous and compound heterozygous ENPP1 pathogenic variants inducing 'Autosomal Recessive Hypophosphatemic Rickets Type 2' (ARHR2) also place patients at risk for DISH and OPLL, possibly due to the loss of inhibitory plasma pyrophosphate (PP_i) which suppresses ectopic calcification and enthesis mineralization. Our findings emphasize the importance of genetic and plasma biomarker screening in the clinical evaluation of DISH and OPLL patients, with plasma PP_i constituting an important new biomarker for the identification of DISH and OPLL patients whose disease course may be responsive to ENPP1 enzyme therapy, now in clinical trials for rare calcification disorders.

Purpose of review: This review aims to summarize (i) the latest evidence on cranial neural crest cells (CNCC) contribution to craniofacial development and ossification; (ii) the recent discoveries on the mechanisms responsible for their plasticity; and (iii) the newest procedures to ameliorate maxillofacial tissue repair.

Recent findings: CNCC display a remarkable differentiation potential that exceeds the capacity of their germ layer of origin. The mechanisms by which they expand their plasticity was recently described. Their ability to participate to craniofacial bone development and regeneration open new perspectives for treatments of traumatic craniofacial injuries or congenital syndromes. These conditions can be life-threatening, require invasive maxillofacial surgery and can leave deep sequels on our health or quality of life. With accumulating evidence showing how CNCC-derived stem cells potential can ameliorate craniofacial reconstruction and tissue repair, we believe a deeper understanding of the mechanisms regulating CNCC plasticity is essential to ameliorate endogenous regeneration and improve tissue repair therapies.

Purpose of review: The purpose of this review is to summarize the scientific evidence published in the past 5 years examining the epidemiology of bone health as it relates to the gut microbiome, across race and ethnicity groups.

Recent findings: The link between the gut microbiome and bone health is well established and is supported by numerous biological mechanisms. However, human study research in this field is dominated by studies of older adults residing in Asian countries. A limited number of epidemiological and randomized controlled trials have been conducted with individuals in other countries; however, they are marked by their racial and ethnic homogeneity, use varied measures of the gut microbiome, and different interventions (where applicable), making comparisons across race and ethnic groups difficult. As the global prevalence of osteoporosis increases, the need for lifestyle interventions is critical. Existing data suggest that racial and ethnic differences in gut microbiome exist. Studies examining the relation between bone health and gut microbial structure and function across diverse racial and ethnic groups are needed to determine appropriate microbiome-based interventions.

Purpose of review: Runt-related transcription factors (RUNX) play critical roles in skeletal development, metabolism, and diseases. In mammals, three RUNX members, namely RUNX1, RUNX2, and RUNX3, play distinct and redundant roles, although RUNX2 is a dominant factor in skeletal development and several skeletal diseases. This review is to provide an overview of the current understanding of RUNX-mediated transcriptional regulation in different skeletal cell types.

Recent findings: Advances in chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) have revealed genome-wide RUNX-mediated gene regulatory mechanisms, including their association with cis-regulatory elements and putative target genes. Further studies with genome-wide analysis and biochemical assays have shed light on RUNX-mediated pioneering action and involvements of RUNX2 in lipid-lipid phase separation. Emerging multi-layered mechanisms of RUNX-mediated gene regulations help us better understanding of skeletal development and diseases, which also provides clues to think how genome-wide studies can help develop therapeutic strategies for skeletal diseases.

Purpose of review: The purpose of this review is to summarize the recently published scientific literature regarding the effects of mitochondrial function and mitochondrial genome mutations on bone phenotype and aging.

Recent findings: While aging and sex steroid levels have traditionally been considered the most important risk factors for development of osteoporosis, mitochondrial function and genetics are being increasingly recognized as important determinants of bone health. Recent studies indicate that mitochondrial genome variants found in different human populations determine the risk of complex degenerative diseases. We propose that osteoporosis should be among such diseases. Studies have shown the deleterious effects of mitochondrial DNA mutations and mitochondrial dysfunction on bone homeostasis. Mediators of such effects include oxidative stress, mitochondrial permeability transition, and dysregulation of autophagy. Mitochondrial health plays an important role in bone homeostasis and aging, and understanding underlying mechanisms is critical in leveraging this relationship clinically for therapeutic benefit.

Purpose of review: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT).

Recent findings: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone. The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.

Purpose of review: Osteoporosis ranks high among morbidities in the elderly as it is a natural process to lose bone, making them susceptible to fractures from minor falls. The cost of managing these patients is staggering. The fractures can be prevented with better care of the elderly, and by treating the major predisposing factor, osteoporosis. Clinicians and scientists, in general, constantly look for early diagnostic and prognostic indicators for osteopenia and osteoporosis to proactively prevent fractures. Dental panoramic radiography (DPR) is a rotational pantomography used for identifying dental pathology in patients. Early signs of osteopenia and osteoporosis can be identified in DPR. The usefulness of notable jaw changes in DPR to predict osteopenia and osteoporosis is still evolving as more studies continue to delve into this concept. The purpose of this review is to present advances made in the practical application of DPR for predicting early onset of osteopenia and osteoporosis.

Recent findings: Dental panoramic radiography, a form of tomography commonly used by dental practitioners, has been the standard of care for decades for detecting dento-alveolar pathology. Several technological advancements have taken place with respect to the use of DPR. These include conversion from plain film to digital radiography, advancements in the manufacture of flat panel detectors, and accurate imaging of the layers of mandible and maxilla that has become possible with appropriate patient positioning within the focal trough of the machine. Improvements in the software infrastructure make it easier to view, enhance, and save the radiographic images. The radiographic appearance of the trabecular bone within the mandible and indices measured from the dental panoramic radiographs focusing on the inferior cortex of the mandible are considered useful tools for identifying asymptomatic individuals with osteoporosis or at risk for developing osteoporosis. These indices apparently correlate with risks of fragility fractures of osteoporosis in other parts of the body. Dental panoramic radiography (DPR) is a commonly used radiographic procedure in dentistry for evaluation of teeth and associated maxillofacial structures. The evaluation of the inferior border of the mandible for reduction or loss of cortical thickness and evaluation of the trabecular bone within the mandible are helpful markers for early signs of osteopenia to identify patients at risk for osteoporosis. This review focused on research advancements on practical application of DPR in early identification of osteopenia and osteoporosis.

Purpose of review: This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery.

Recent findings: Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.

Purpose of review: Increasing bone mineral accrual during childhood might delay the onset of osteoporosis. We discuss the scientific evidence for early life approaches to optimising skeletal health.

Recent findings: There is an ever-growing body of evidence from observational studies suggesting associations between early life exposures, particularly during foetal development, and bone mineral density (BMD). The findings of such studies are often heterogeneous, and for some exposures, for example, maternal smoking and alcohol intake in pregnancy or age at conception, intervention studies are not feasible. The most frequently studied exposures in intervention studies are calcium or vitamin D supplementation in pregnancy, which overall suggest positive effects on offspring childhood BMD. Maternal calcium and/or vitamin D supplementation during pregnancy appear to have positive effects on offspring BMD during early childhood, but further long-term follow-up is required to demonstrate persistence of the effect into later life.