Current Osteoporosis Reports最新文献

Purpose of review: Review recent literature investigating the relationship between bone health and sleep/circadian disruptions (e.g., abnormal sleep duration, night shift work).

Recent findings: Short and long sleep are associated with low bone mineral density (BMD). Recent data from observational studies identified an increased risk of fracture in women with short sleep. Studies suggest that age, sex, weight change, and concurrent circadian misalignment may modify the effects of sleep restriction on bone metabolism. Interventional studies demonstrate alterations in bone metabolism and structure in response to circadian disruption that could underlie the increased fracture risk seen with night shift work. The effects of sleep and circadian disruption during adolescence may have lifelong skeletal consequences if they adversely impact bone modeling. Data suggest that short sleep and night shift work negatively impact bone metabolism and health. Rigorous studies of prevalent sleep and circadian disruptions are needed to determine mechanisms and develop prevention strategies to optimize lifelong skeletal health.

Purpose of review: To review the mechanisms by which vitamin D and its metabolites regulate the immune system to facilitate the ability of the body to prevent and/or treat SARS-CoV2 and other respiratory infections and encourage further research into the role that vitamin D supplementation plays in preventing/treating such infections.

Recent findings: Vitamin D deficiency is associated with an increased risk of SARS-CoV2 and other respiratory infections. Clinical trials in general demonstrate that correction of vitamin D deficiency reduces the risk of hospitalization, ICU admission, and death from SARS-CoV2 infection. The airway epithelium and alveolar macrophages express the enzyme, CYP27B1, that produces the active metabolite of vitamin D, 1,25(OH)₂D, and the vitamin D receptor, VDR. Vitamin D and its metabolites promote the innate immune response, which provides the first line of defense against viral and bacterial infections while restricting the adaptive immune response, which if unchecked promotes the inflammatory response leading to the acute respiratory distress syndrome and death. The rationale for treating vitamin D deficiency to reduce the risk of SARS-CoV2 infection and supplementing patients with vitamin D early in the course of SARS-CoV2 infection rests primarily on the ability of vitamin D metabolites to promote an effective immune response to the infection.

Purpose of review: Periosteal apposition and endosteal remodeling regulate cortical bone expansion and thickness, both critical determinants of bone strength. Yet, the cellular characteristics and local or paracrine factors that regulate the periosteum and endosteum remain largely elusive. Here we discuss novel insights in cortical bone growth, expansion, and homeostasis, provided by the study of Secreted Frizzled Receptor Protein 4 (Sfrp4), a decoy receptor for Wnt ligands.

Recent findings: SFRP4 loss-of function mutations cause Pyle disease, a rare skeletal disorder characterized by cortical bone thinning and increased fragility fractures despite increased trabecular bone density. On the endosteal surface, Sfrp4-mediated repression of non-canonical Wnt signaling regulates endosteal resorption. On the periosteum, Sfrp4 identifies as a critical functional mediator of periosteal stem cell/progenitor expansion and differentiation. Analysis of signaling pathways regulating skeletal stem cells/progenitors provides an opportunity to advance our understanding of the mechanisms involved in cortical bone biology.

Purpose of review: Osteoblasts are responsible for bone matrix production during bone development and homeostasis. Much is known about the transcriptional regulation and signaling pathways governing osteoblast differentiation. However, less is known about how osteoblasts obtain or utilize nutrients to fulfill the energetic demands associated with osteoblast differentiation and bone matrix synthesis. The goal of this review is to highlight and discuss what is known about the role and regulation of bioenergetic metabolism in osteoblasts with a focus on more recent studies.

Recent findings: Bioenergetic metabolism has emerged as an important regulatory node in osteoblasts. Recent studies have begun to identify the major nutrients and bioenergetic pathways favored by osteoblasts as well as their regulation during differentiation. Here, we highlight how osteoblasts obtain and metabolize glucose, amino acids, and fatty acids to provide energy and other metabolic intermediates. In addition, we highlight the signals that regulate nutrient uptake and metabolism and focus on how energetic metabolism promotes osteoblast differentiation. Bioenergetic metabolism provides energy and other metabolites that are critical for osteoblast differentiation and activity. This knowledge contributes to a more comprehensive understanding of osteoblast biology and may inform novel strategies to modulate osteoblast differentiation and bone anabolism in patients with bone disorders.

Purpose of review: Fibroblast growth factor 23 (FGF23) is a bone- and bone marrow-derived hormone that is critical to maintain phosphate homeostasis. The principal actions of FGF23 are to reduce serum phosphate levels by decreasing kidney phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. FGF23 deficiency causes hyperphosphatemia and ectopic calcifications, while FGF23 excess causes hypophosphatemia and skeletal defects. Excess FGF23 also correlates with kidney disease, where it is associated with increased morbidity and mortality. Accordingly, FGF23 levels are tightly regulated, but the mechanisms remain incompletely understood.

Recent findings: In addition to bone mineral factors, additional factors including iron, erythropoietin, inflammation, energy, and metabolism regulate FGF23. All these factors affect Fgf23 expression, while some also regulate FGF23 protein cleavage. Conversely, FGF23 may have a functional role in regulating these biologic processes. Understanding the bi-directional relationship between FGF23 and non-bone mineral factors is providing new insights into FGF23 regulation and function.