Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism.

Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover. The objective of this study was to characterize the bone expression of these proteins by immunohistochemistry and correlate these results with those of bone histomorphometry before and after parathyroidectomy. We studied bone biopsies that were obtained from 23 patients before and 12 months after parathyroidectomy. We observed an improvement in bone microarchitecture, but impaired mineralization after parathyroidectomy. We found significant increases in sclerostin and osteoprotegerin expression and a decrease in the RANKL/osteoprotegerin ratio after parathyroidectomy, suggesting that their expression is regulated by parathormone. These proteins correlated with structural and bone formation parameters. We conclude that after parathyroidectomy, significant changes occur in the bone expression of osteocyte proteins and that these proteins potentially regulate bone remodeling.

Comparison of clinical, biochemical and histomorphometric analysis of bone biopsies in dialysis patients with and without fractures.

Chronic kidney disease-mineral bone disorders (CKD-MBD) are associated with increased risk of fracture. Studies report about 3% of fractures in CKD patients, and these occur earlier than in the general population, namely 16 and 13 years earlier for men and women, respectively. Better understanding of the pathophysiology of fractures would probably contribute to new therapeutic approaches. This study aimed to evaluate report of long bone fractures from a bone biopsies bank from patients on hemodialysis and compare clinical and biochemical characteristics, as well as the results of the histomorphometric analysis of trabecular and cortical bone of these patients with a control group (without fractures), paired for age, gender, and time on hemodialysis. Bone proteins (SOST, DMP1 and MEPE) were evaluated by immunohistochemistry. Seventeen patients with fracture and controls were studied. Fracture prevalence was 0.82/1000 patients/year. Serum phosphorus levels were significantly lower in the fracture group. Histomorphometric analysis revealed that all the patients had high turnover disease, and the fracture group had smaller volume and trabecular thickness, greater osteoid surface, smaller eroded surface, smaller mineralizing surface, formation rate and longer mineralization lag time when compared to controls; the DMP1 expression in the cortical bone was smaller and the SOST in the trabecular bone was higher in fractured patients. As conclusion, we found low prevalence of fractures. Both groups had high turnover disease, but the fractured ones presented more impaired bone microarchitecture, as well as lower formation and greater mineralization defect. Bone proteins expression correlated with parameters involved in bone remodeling.

The unexpected presence of iron in bone biopsies of hemodialysis patients.

PURPOSE: Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics. METHODS: This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital. RESULTS: Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload. CONCLUSION: Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.

The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis.

PURPOSE: Osteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization-TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells. METHODS: We studied 29 new living-donor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry. RESULTS: Some bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT. CONCLUSION: In conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.

High-salt intake induces cardiomyocyte hypertrophy in rats in response to local angiotensin II type 1 receptor activation.

Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension.