Bone, inflammation and the bone marrow niche in chronic kidney disease: what do we know?

Abstract

Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase). Further, in recent years the close link between bone and inflammation has been better appreciated and a wide range of chronic inflammatory states (from rheumatoid arthritis to ageing) are being explored to discover the biochemical changes that ultimately lead to bone loss and OP. Also, it has been acknowledged that the concept of the bone-vascular axis may explain, for example, the relationship between bone metabolism and vessel wall diseases like atherosclerosis and arteriosclerosis, with potential involvement of a number of cytokines and metabolic pathways. A very important discovery in bone physiology is the bone marrow (BM) niche, the functional unit where stem cells interact, exchanging signals that impact on their fate as bone-forming cells or immune-competent haematopoietic elements. This new element of bone physiology has been recognized to be dysfunctional in diabetes (so-called diabetic mobilopathy), with possible clinical implications. In our opinion, ROD, the metabolic bone disease of renal patients, will in the future probably be identified as a cause of BM niche dysfunction. An integrated view of bone, which includes the BM niche, now seems necessary in order to understand the complex clinical entity of chronic kidney disease-mineral and bone disorders and its cardiovascular burden. Bone is thus becoming a recurrently considered paradigm for different inter-organ communications that needs to be considered in patients with complex diseases.

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

“…Currently, the burgeoning field of osteoimmunology mainly focuses on the investigation of the interaction of the immune system in the skeleton with bone physiology, of which there exist many chronic inflammatory diseases concomitant with resorption-associated bone loss, including rheumatoid arthritis (RA), spinal cord injury (SCI), and aging-related osteoporosis (OP), etc [85][86][87][88][89] . Though the underlying mechanism whereby some proinflammatory factors induce resorption-associated bone loss remains fully unknown, it is hypothesized that osteocyte apoptosis might have a profound role in regulating bone homeostasis under these chronic inflammatory diseases.…”

Mineral and Electrolyte Disorders With SGLT2i Therapy

“…Chronic hyperglycemia and AGEs accumulation also contribute to inflammation, a pathophysiological hallmark of diabetes. Besides cardiovascular complications, any chronic inflammatory state can be expected to affect bone cell activity and bone health …”

“…Besides cardiovascular complications, any chronic inflammatory state can be expected to affect bone cell activity and bone health. (40) Hence, all these metabolic derangements may predispose to mineral metabolism abnormalities and future efforts are needed to disentangle the impact of SGLT2is on bone health, particularly if advanced age and CKD coexist.…”

Physical Activity in the Prevention of Development and Progression of Kidney Disease in Type 1 Diabetes

“…Increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress, and acidosis, as well as susceptibility to infections and intestinal dysbiosis, all contribute to chronic inflammation that is adversely associated with albuminuria and measures of kidney function [ 27 , 28 ]. In addition, pro-inflammatory molecules, such as TNF-α, are potent triggers of osteoclast activation and contribute to the adverse effects on the bone and skeletal muscle metabolism with resultant bone resorption, sarcopenia and cachexia, and also vessel wall diseases [ 29 ]. Exercise remains an important tool in reversing the inflammatory processes and their negative consequences [ 30 , 31 ].…”