Current Osteoporosis Reports最新文献

Purpose of review: Genetic studies in humans and animal models have improved our understanding of the role of numerous genes in the etiology of nonsyndromic tooth agenesis (TA). The purpose of this review is to discuss recently identified genes potentially contributing to TA.

Recent findings: Despite research progress, understanding the genetic factors underlying nonsyndromic TA has been challenging given the genetic heterogeneity, variable expressivity, and incomplete penetrance of putatively pathogenic variants often observed associated with the condition. Next-generation sequencing technologies have provided a platform for novel gene and variant discoveries and informed paradigm-shifting concepts in the etiology of TA. This review summarizes the current knowledge on genes and pathways related to nonsyndromic TA with a focus on recently identified genes/variants. Evidence suggesting possible multi-locus variation in TA is also presented.

Purpose of review: Chemotherapy drugs combat tumor cells and reduce metastasis. However, a significant side effect of some chemotherapy strategies is loss of skeletal muscle and bone. In cancer patients, maintenance of lean tissue is a positive prognostic indicator of outcomes and helps to minimize the toxicity associated with chemotherapy. Bone-muscle crosstalk plays an important role in the function of the musculoskeletal system and this review will focus on recent findings in preclinical and clinical studies that shed light on chemotherapy-induced bone-muscle crosstalk.

Recent findings: Chemotherapy-induced loss of bone and skeletal muscle are important clinical problems. Bone antiresorptive drugs prevent skeletal muscle weakness in preclinical models. Chemotherapy-induced loss of bone can cause muscle weakness through both changes in endocrine signaling and mechanical loading between muscle and bone. Chemotherapy-induced changes to bone-muscle crosstalk have implications for treatment strategies and patient quality of life. Recent findings have begun to determine the role of chemotherapy in bone-muscle crosstalk and this review summarizes the most relevant clinical and preclinical studies.

Purpose of review: Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where suppression of bone resorption is desired. However, denosumab discontinuation is associated with rebound increase in bone resorption and subsequent loss in bone mass and a rapid return to baseline fracture risk. We review recent data on the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind this phenomenon.

Recent findings: Osteoclasts have been considered to be highly specialised cells that undergo apoptosis after fulfilling their function of bone resorption. However, recent studies suggest that osteoclasts are longer lived cells which migrate through vasculature and are capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. The life cycle of the osteoclast is more complex than previously appreciated. Osteoclast recycling provides a novel mechanistic framework to examine changes in osteoclast biology in response to treatment of bone diseases and provides an exciting new avenue towards personalised medicine.

Purpose of review: In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system.

Recent findings: Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α₂δ₁ auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α₂δ₁ subunit where GBP and PGB can alter calcium-mediated signaling events. In tissues such as bone, muscle, and cartilage, α₂δ₁ has important roles in skeletal formation, mechanosensation, and normal tissue function/repair that may be affected by chronic use of gabapentinoids. Long-term use of gabapentinoids is associated with detrimental musculoskeletal outcomes, including increased fracture risk. Therefore, understanding potential complications is essential for clinicians to guide appropriate treatments.

Purpose of review: Cognitive impairment is associated with obesity, sarcopenia, and osteoporosis. However, no critical appraisal of the literature on the relationship between musculoskeletal deficits and cognitive impairment, focusing on the epidemiological evidence and biological mechanisms, has been published to date. Herein, we critically evaluate the literature published over the past 3 years, emphasizing interesting and important new findings, and provide an outline of future directions that will improve our understanding of the connections between the brain and the musculoskeletal system.

Recent findings: Recent literature suggests that musculoskeletal deficits and cognitive impairment share pathophysiological pathways and risk factors. Cytokines and hormones affect both the brain and the musculoskeletal system; yet, lack of unified definitions and standards makes it difficult to compare studies. Interventions designed to improve musculoskeletal health are plausible means of preventing or slowing cognitive impairment. We highlight several musculoskeletal health interventions that show potential in this regard.

Purpose of review: This review summarizes recent investigations into the cellular and molecular effects of skeletal aging on the inflammatory response and stem cell function after fracture.

Recent findings: Proper regulation of the inflammatory phase of fracture healing is essential. Aging is associated with chronic inflammation, which inhibits bone formation and promotes bone resorption. Osteogenic differentiation and anti-senescence pathways in skeletal stem cells are impaired in geriatric fractures. As the population ages, fragility fractures will continue to represent a significant clinical problem, which will require innovative clinical solutions. Skeletal stem cells in geriatric individuals demonstrate defects in anti-senescence pathways that lead to impaired osteogenic differentiation in vitro in humans. Small molecule-based therapies can partially reverse the aging phenotype. In the future, molecular- or cell-based therapies modulating either inflammatory cells or skeletal stem cells represent potential therapeutic targets to augment contemporary fracture healing interventions in osteoporotic or aging individuals.

Purpose of review: Aging leads to decline in bone mass and quality starting at age 30 in humans. All mammals undergo a basal age-dependent decline in bone mass. Osteoporosis is characterized by low bone mass and changes in bone microarchitecture that increases the risk of fracture. About a third of men over the age of 50 years are osteoporotic because they have higher than basal bone loss. In women, there is an additional acute decrement in bone mass, atop the basal rate, associated with loss of ovarian function (menopause) causing osteoporosis in about half of the women. Both genetics and environmental factors such as smoking, chronic infections, diet, microbiome, and metabolic disease can modulate basal age-dependent bone loss and eventual osteoporosis. Here, we review recent studies on the etiology of age-dependent decline in bone mass and propose a mechanism that integrates both genetic and environmental factors.

Recent findings: Recent findings support that aging and menopause dysregulate the immune system leading to sterile low-grade inflammation. Both animal models and human studies demonstrate that certain kinds of inflammation, in both men and women, mediate bone loss. Senolytics, meant to block a wide array of age-induced effects by preventing cellular senescence, have been shown to improve bone mass in aged mice. Based on a synthesis of the recent data, we propose that aging activates long-lived tissue resident memory T-cells to become senescent and proinflammatory, leading to bone loss. Targeting this population may represent a promising osteoporosis therapy. Emerging data indicates that there are several mechanisms that lead to sterile low-grade chronic inflammation, inflammaging, that cause age- and estrogen-loss dependent osteoporosis in men and women.

Purpose of review: Weight loss is recommended for improving glycemic control and reducing cardiovascular risk factors in persons with diabetes. However, both diabetes and weight loss have been associated with detrimental skeletal health. This review aims to summarize recent study findings on the effects of lifestyle interventions for weight loss on skeletal health among persons with type 2 diabetes (T2D).

Recent findings: A few large-scale observational studies have demonstrated an increased fragility fracture risk associated with weight loss among persons with T2D. Randomized control trials in persons with T2D also have shown that intentional lifestyle interventions for weight loss are associated with a greater decrease in bone mineral density (BMD) and an increase in the risk of fracture. The biological mechanisms underlying the compromised bone health during lifestyle interventions for weight loss are complex and not yet conclusive. However, there is evidence to suggest that bone loss and increased fracture risk during intentional weight loss may be mitigated by some intervention approaches, such as high protein intake, calcium supplementation, and resistance and balance training. There is still a lack of studies investigating the effects of different interventions for weight loss on skeletal health among persons with T2D. However, certain types of diet and physical activity intervention combined with bone monitoring and fracture risk prediction may help achieve weight loss goals and maintain skeletal health among persons with T2D during intentional weight loss.

Purpose of review: The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia.

Recent findings: Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism have been implicated in cancer-induced regeneration defect and muscle loss. Moreover, we review novel in vitro and animal models including promising new drug candidates for bone metastases and cancer cachexia. Preservation of bone health could be highly beneficial for maintaining muscle mass and function. Therefore, a better understanding of molecular pathways implicated in bone and muscle crosstalk in metastatic disease may provide new insights and identify new strategies to improve current anticancer therapeutics.

Purpose of review: Although COVID-19 was originally characterized as a respiratory disease, recent findings have shown lingering side effects in those who have recovered, and much is still unknown about the long-term consequences of the illness. Thus, the potential of unearthing multi-system dysfunction is high, with current data revealing significant impacts on musculoskeletal health.

Recent findings: Multiple animal models of COVID-19 infection have revealed significant post-infection bone loss at several different skeletal sites. While how this loss occurred is unknown, this current review discusses the primary bone loss studies, and examines the possible mechanisms of action including: direct infection of bone marrow macrophages or hematopoietic progenitors, a proinflammatory response as a result of the COVID-19 induced cytokine storm, and/or a result of hypoxia and oxidative stress. This review will further examine how therapeutics used to treat COVID-19 affect the skeletal system. Finally, this review will examine the possible consequence that delayed care and limited healthcare accessibility has on musculoskeletal-related patient outcomes. It is important to investigate the potential impact COVID-19 infection has on musculoskeletal health.