“Take My Bone Away?” Hypoxia and bone: A narrative review

Hannah, Scott S.; McFadden, Sonyia; McNeilly, Andrea; McClean, Conor

doi:10.1002/jcp.29921

Cited by 39 publications

(38 citation statements)

References 197 publications

(475 reference statements)

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“…It has been suggested that hypoxia may induce an osteogenic-angiogenic response, but also stimulate excessive OCL activity. Moreover, several hypoxia-associated factors may influence bone metabolism by determining changes in energy metabolism and increasing the generation of reactive oxygen species (ROS), mechanisms that may impair the physiological acid-base balance [58]. Practically, there is a metabolic reprogramming during OBL differentiation so that, while the aerobic glycolysis (one molecule of glucose is split into two pyruvate molecules) increases during the OBL differentiation process (Table 2), the mitochondrial respiration and energy production progressively decrease, reaching their minimum in the mature OBL [59].…”

Section: "Fuel" Selection According To Bone Cells Differentiation Stepsmentioning

confidence: 99%

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Merlotti

Cosso

Eller-Vainicher

et al. 2021

IJMS

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The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a “poor” quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

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Section: "Fuel" Selection According To Bone Cells Differentiation Stepsmentioning

confidence: 99%

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Merlotti

Cosso

Eller-Vainicher

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In bone cancers, hypoxia results from increased proliferation of cancer cells in association with a high rate of oxygen consumption, and from the intrinsic hypoxia of the bone microenvironment. Indeed, hypoxia greatly influences bone biology and physiology [22]. As a demonstration, in the medullary cavity of animal models, pO 2 values range from 11.7 to 31.7 mm Hg (1.5-4.2%), with a mean of 20.4 mm Hg (2.7%) [23].…”

Section: Altered Tumour Metabolism and Intratumoural Acidosis In Bone Sarcomasmentioning

confidence: 99%

Acid Microenvironment in Bone Sarcomas

Pompo

Cortini

Baldini

et al. 2021

Cancers

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In bone sarcomas, extracellular proton accumulation is an intrinsic driver of malignancy. Extracellular acidosis increases stemness, invasion, angiogenesis, metastasis, and resistance to therapy of cancer cells. It reprograms tumour-associated stroma into a protumour phenotype through the release of inflammatory cytokines. It affects bone homeostasis, as extracellular proton accumulation is perceived by acid-sensing ion channels located at the cell membrane of normal bone cells. In bone, acidosis results from the altered glycolytic metabolism of bone cancer cells and the resorption activity of tumour-induced osteoclasts that share the same ecosystem. Proton extrusion activity is mediated by extruders and transporters located at the cell membrane of normal and transformed cells, including vacuolar ATPase and carbonic anhydrase IX, or by the release of highly acidic lysosomes by exocytosis. To date, a number of investigations have focused on the effects of acidosis and its inhibition in bone sarcomas, including studies evaluating the use of photodynamic therapy. In this review, we will discuss the current status of all findings on extracellular acidosis in bone sarcomas, with a specific focus on the characteristics of the bone microenvironment and the acid-targeting therapeutic approaches that are currently being evaluated.

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“…The BM environment is hypoxic by its nature and this is critical for the activity of hematological stem cells and may also be an important underlying cause of metastasis of various tumor types to the BM (28)(29)(30). This is an important consideration, as the BM is already hypoxic and it remains unclear if engrafted MM tumor cells establish a greater hypoxic gradient similar to what is observed in solid tumors.…”

Section: Hypoxia In Hematological Tumors Bone Marrowmentioning

confidence: 99%

“…Leukemias develop from the uncontrolled hematopoiesis of stem cells in the BM and it seems that hypoxia plays a critical role in maintaining these cancerous stem cells ( 34 ). In contrast, MM and lymphomas form “solid” tumor masses and likely share some physiological similarities to solid tumors, but again, the exact role of hypoxia in MM remains unclear ( 8 , 30 ).…”

Section: Hypoxia In Hematological Tumorsmentioning

confidence: 99%

Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?

et al. 2021

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Multiple myeloma (MM) is an incurable cancer arising from malignant plasma cells that engraft in the bone marrow (BM). The physiology of these cancer cells within the BM microenvironment (TME) plays a critical role in MM development. These processes may be similar to what has been observed in the TME of other (non-hematological) solid tumors. It has been long reported that within the BM, vascular endothelial growth factor (VEGF), increased angiogenesis and microvessel density, and activation of hypoxia-induced transcription factors (HIF) are correlated with MM progression but despite a great deal of effort and some modest preclinical success the overall clinical efficacy of using anti-angiogenic and hypoxia-targeting strategies, has been limited. This review will explore the hypothesis that the TME of MM engrafted in the BM is distinctly different from non-hematological-derived solid tumors calling into question how effective these strategies may be against MM. We further identify other hypoxia-mediated effectors, such as hypoxia-mediated acidification of the TME, oxygen-dependent metabolic changes, and the generation of reactive oxygen species (ROS), that may prove to be more effective targets against MM.

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“Take My Bone Away?” Hypoxia and bone: A narrative review

Cited by 39 publications

References 197 publications

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Acid Microenvironment in Bone Sarcomas

Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?

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