Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.

Effects of Different Hemodialysis Treatments on Abnormal Mineral and Bone Metabolism in Patients with Chronic Renal Failure

Objective:To investigate the effects of different hemodialysis treatments on abnormal mineral and bone metabolism in patients with chronic renal failure.Methods:A random number table was used to divide 80 patients with chronic renal failure admitted to our hospital from January 2018 to January 2019 into 2 groups,with 40 cases in each group.Group A was treated with low-flux hemodialysis,and group B was treated with high-flux hemodialysis.The related indicators of mineral and bone metabolism of the two groups were compared.Results:Before treatment,the blood calcium,blood phosphorus,intact parathyroid hormone(iPTH),type I procollagen amino terminal peptide(PINP),fibroblast growth factor 23(FGF23),serum creatinine(Scr)indicators of the two groups were compared.The difference was not statistically significant(P>0.05);After treatment,the blood calcium levels of the two groups were higher than before treatment,the blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than before treatment,and the blood calcium level of group B was higher than that of group A,while blood phosphorus,iPTH,PINP,FGF23,and Scr levels were lower than group A,the difference was statistically significant(P<0.05).Conclusion:Compared with low-flux hemodialysis,patients with chronic renal failure treated with highflux hemodialysis have better results,which can correct abnormal bone metabolism and improve Scr levels.