Current Osteoporosis Reports最新文献

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.

Purpose of review: The purpose of this review is to explore the multifaceted roles of the ERI1 exoribonuclease, particularly in RNA metabolism and bone development, and to address the genotype-phenotype complexity in patients and mice with ERI1 pathogenic variants.

Recent findings: The 3'-to-5' exoribonuclease 1 encoded by the ERI1 gene performs a variety of biologically essential functions, including modulating RNA interference, heterochromatin formation, rRNA maturation, and histone mRNA degradation. Recently, the relationship between ERI1 variants and human skeletal dysplasia has garnered increasing attention. In a phenotypic dichotomy associated with bi-allelic ERI1 variants, patients with at least one missense pathogenic variant exhibited severe spondylo-epi-metaphyseal dysplasia (SEMD), while those with bi-allelic nonsense pathogenic variant only presented mild anomaly in digits. The biological mechanisms underlying the bone dysplasia caused by ERI1 pathogenic variants remain unknown. Although Eri1 knockout (KO) mice showed mild skeletal phenotypes, neither SEMD nor digital anomaly were found, further underscoring a complex genotype-phenotype relationship of ERI1 pathogenic variants. We systematically reviewed the advances in exploring the multiple functions of ERI1 with emphasis on its roles in RNA metabolism and skeletal development. Our review would contribute to the understanding of the phenotypic spectrum caused by ERI1 pathogenic variants and the limitations of existing disease models in revealing the corresponding pathomechanism.

Purpose: This review focuses on recent findi+ngs regarding the management of adverse skeletal effects following weight loss in people living with obesity (PwO). We summarize the guidelines provided by various societies for the prevention and treatment of osteoporosis resulting from bariatric surgery. Next, we discuss the use of traditional antiosteoporosis medications in this population.

Recent findings: Guidelines for preventing and treating osteoporosis resulting from bariatric surgery have been recently provided by various societies setting specific treatment criteria for postmenopausal women and men aged ≥ 50 years, based on the occurrence of fragility fractures and/or T-score thresholds. Several studies have highlighted the positive effects of lifestyle changes in preventing high-turnover bone loss; however, data on fracture outcomes are currently unavailable. It is generally accepted that following bariatric procedures, sufficient intake of calcium, vitamin D, and protein, along with regular exercise incorporating progressive, supervised resistance training, is crucial to counteract negative impacts on bone. Regarding the need for medications to combat osteoporosis, most societies recommend zoledronic acid as the preferred choice. This preference is due to the problems associated with oral bisphosphonates, including poor tolerance and absorption issues. Denosumab is typically considered the second choice when bisphosphonates are not suitable or well tolerated. Two randomized controlled studies have recently demonstrated the effectiveness and safety of zoledronic acid and denosumab in addressing high-turnover bone loss. Although guidelines exist for managing skeletal health before and after bariatric surgery, more research is required to validate these recommendations and the use of anti-osteoporosis medications.

Purpose of review: The present review will examine bone disease in mastocytosis, analyze the existing literature on its management, and propose a strategy for osteoporosis treatment in systemic mastocytosis. This strategy is based on both the available scientific evidence and the experience gained at our expert center (CEREMAST).

Recent findings: Systemic mastocytosis is a rare disorder, primarily affecting the bone and leading to osteoporosis, bone pain, and bone structural abnormalities. While traditionally described in indolent systemic mastocytosis, bone involvement is also observed in bone marrow mastocytosis. The true prevalence of systemic mastocytosis is likely underreported, highlighting the importance for clinicians to be familiar with the condition, particularly in cases of osteoporosis. Osteoporosis management typically involves bisphosphonates, with potential benefits from combining them with specific treatments like interferon in severe osteoporosis with vertebral fractures. The potential of new mast cell-targeting molecules to treat bone involvement needs to be demonstrated. This review provides a guide for osteoporosis and bone pain management in systemic mastocytosis.

Purpose of review: To assess the efficacy of calcium supplements in preventing fractures, and to review their adverse effects, particularly on the cardiovascular system.

Recent findings: There is now a large body of trial evidence demonstrating that calcium supplements do not prevent fractures in community-dwelling adults. They commonly produce gastrointestinal side-effects, sometimes serious, and increase the risk of renal calculi. Meta-analyses of adverse events from clinical trials suggest that the risk of MI is increased by 10-20% with calcium supplementation, though dietary calcium intake does not appear to be a cardiac risk factor. Ingestion of a calcium bolus increases circulating calcium concentrations for the following 8 h, accompanied by acute increases in blood coagulability and calcification propensity, with blood pressures > 5 mmHg higher than placebo-treated individuals. Mendelian randomization studies demonstrate that circulating calcium levels are a significant risk factor for cardiovascular disease, so the acute calcium-elevating effect of supplements might contribute to increased cardiovascular risk. The current balance of evidence suggests that calcium supplements have little role in the prevention or treatment of osteoporosis, since estrogen and bisphosphonates prevent fractures without their co-administration. Specific studies are needed to address whether calcium is benficial with anabolic bone medicines.

Purpose of review: This review aims to summarise recent evidence on the effects of dietary patterns on the risk of bone fractures and sarcopenia.

Recent findings: Several dietary patterns have been investigated in relation to musculoskeletal health, including Mediterranean Dietary Patterns (MDP), Dietary Inflammatory Indices, vegetarian and vegan diets. Adherence to 'healthier' dietary patterns appears to be protective against fractures and sarcopenia, with the strongest protective associations found between the MDP and fractures. Individuals following vegan or vegetarian eating patterns need to be aware of calcium and vitamin D requirements to maintain musculoskeletal health. Although more healthy dietary patterns may be protective for musculoskeletal health the current evidence base is limited by variation in the construction of dietary pattern scores and reported outcome measures. Future research should fully report scoring methods, intakes of dietary components across scoring groups or categories, and consider outcome measures that allow for better comparison between studies.

Purpose of review: The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease.

Recent findings: Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption. The role of PRR engagement on bone remodeling has been best described as a result of activated macrophages secreting effector molecules that reshape the characteristics of bone-resident cells. However, it is being increasingly recognized that local bone resident-cells like osteoclasts and osteoblasts possess an arsenal of PRRs. The engagement of these PRRs by stimuli in the bone niche can drive cell-autonomous (aka cell-intrinsic) responses that, in turn, impact bone-remodeling dramatically, irrespective of immune cell effectors. Indeed, this vital role for cell-autonomous innate immune responses is evident in how reduced PRR activity within osteoclast progenitors correlates with their reduced differentiation and abnormal bone remodeling. Further, cell-intrinsic PRR activity has now been shown to influence the behavior of osteoblasts, osteocytes and other local immune/non-immune cell populations. However, distinct PRR families have varying impact on bone homeostasis and inflammation, emphasizing the importance of investigating these different nodes of innate immune signaling in bone cells to better identify how they synergistically and/or antagonistically regulate bone remodeling in the course of an immune response. Innate immune sensing within bone resident cells is a critical determinant for bone remodeling in health and disease.

Purpose of review: To present race and ethnicity as evidence of the need for precision medicine in renal osteodystrophy.

Recent findings: Previously described racial-ethnic differences in bone persist in recent data on fracture risk in the healthy and CKD populations. These differences have historically been noted between Black and White participants, but recent data suggests racial-ethnic differences in bone are more intricate than previously recognized. A reflection on skeletal differences within the general, non-CKD population, provides a context to better understand skeletal differences by race within CKD. Despite numerous studies demonstrating racial differences in skeletal microarchitecture, fracture risk and skeletal biomarkers, further evidence is needed to pinpoint the etiology of racial differences and to allow precision treatment that reflects the individual patient, regardless of race. In the end, race is currently our most saliant example of the need for a precision medicine approach to the treatment of renal osteodystrophy.

Purpose of review: To describe the diagnosis, classification, and modern management of lateral compression fragility fractures of the pelvis.

Recent findings: Practice patterns are shifting toward early operative treatment of fragility fractures of the pelvis among patients who are unable to mobilize or whose injuries demonstrate occult instability on stress imaging. Early internal fixation appears to decrease pain, facilitate mobilization, accelerate hospital discharge, and minimize morbidity in this population. Lateral compression pelvic ring injuries are the most common type of fragility fracture of the pelvis. Similar to fragility fractures of the hip, lateral compression fragility fractures of the pelvis are typically sustained in a ground level fall. These injuries are associated with long acute hospital and post-acute facility admissions, loss of physical function, loss of independence, mortality, anxiety, sleep disturbance, and caregiver burnout. Unlike hip fractures, for which urgent operative treatment and early mobilization reduce mortality, lateral compression fragility fractures of the pelvis are commonly treated without surgery. Recommendations for nonoperative management of these injuries in older adults may be inappropriately generalized from studies of younger patient populations with high-energy mechanisms of pelvis fracture. However, strong evidence to support early internal fixation of these injuries practice is lacking. High quality investigations of early surgical intervention for lateral compression fragility fractures of the pelvis are needed to guide care for these patients.

Purpose of review: Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD.

Recent findings: BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.