Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover.

Renal osteodystrophy (ROD) is a complex and serious complication of chronic kidney disease (CKD), a major global health problem caused by loss of renal function. Currently, the gold standard to accurately diagnose ROD is based on quantitative histomorphometric analysis of trabecular bone. Although this analysis encompasses the evaluation of osteoblast and osteoclast number/activity, tfigurehe interest in osteocytes remains almost nihil. Nevertheless, this cell type is evidenced to perform a key role in bone turnover, particularly through its production of various bone proteins, such as sclerostin. In this study, we aim to investigate, in the context of ROD, to which extent an association exists between bone turnover and the abundance of osteocytes and osteocytic sclerostin expression in both the trabecular and cortical bone compartments. Additionally, the effect of parathyroid hormone (PTH) on bone sclerostin expression was examined in parathyroidectomized rats. Our results indicate that PTH exerts a direct inhibitory function on sclerostin, which in turn negatively affects bone turnover and mineralization. Moreover, this study emphasizes the functional differences between cortical and trabecular bone, as the number of (sclerostin-positive) osteocytes is dependent on the respective bone compartment. Finally, we evaluated the potential of sclerostin as a marker for CKD and found that the diagnostic performance of circulating sclerostin is limited and that changes in skeletal sclerostin expression occur more rapidly and more pronounced. The inclusion of osteocytic sclerostin expression and cortical bone analysis could be relevant when performing bone histomorphometric analysis for diagnostic purposes and to unravel pathological mechanisms of bone disease.

Relationship between intraoperative measured parameters of parathyroid gland and pathological patterns in patients with secondary hyperparathyroidism.

BACKGROUND: The hyperplastic patterns of parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) are critical for surgical indication and deciding on the approach. Earlier histopathological investigations have suggested the occurrence of an initial increase in the parathyroid cells, with a normal lobular structure (diffuse hyperplasia, DH). After this, the PTGs become hyperplastic with some nodules (nodular hyperplasia, NH). The current study aimed to explore the relationship between the intraoperative measurements of weight, volume, and maximal diameter of dissected PTGs and the histopathological diagnosis of SHPT patients with end-stage renal disease. METHODS: A total of 182 SHPT patients who received parathyroidectomy (PTX) were retrospectively enrolled. Altogether 21 patients were selected as having at least one diffuse polyclonal hyperplasia PTG. Intraoperative measurements of weight, volume, and maximal diameter of dissected PTGs were compared between tissues with DH and NH. RESULTS: Intraoperative dissected PTGs were verified histologically. The differences in the intraoperative measurements of weight, volume, maximal diameter, and the combination of the three measurements between the DH and the NH PTGs groups were significant (P=0.000), and the values of area under the ROC curve (AUCs) were 0.824 (95% CI: 0.731-0.918), 0.812 (95% CI: 0.716-0.908), 0.746 (95% CI: 0.633-0.860), and 0.851 (95% CI: 0.768-0.935), respectively, with cut-off values of the three parameters being 0.19 g, 206.3 mm3, and 10.5 mm, respectively. CONCLUSIONS: The measurement of weight, volume, and maximal diameter of dissected PTGs is a possible alternative to assess the hyperplasia patterns of the dissected PTGs. It is a promising reference for the ultrasound prediction of pathological patterns of PTGs.

Therapeutic efficacy of two surgical methods on the secondary hyperparathyroidism.

BACKGROUND: This study aimed to investigate the clinical efficacy of two surgical methods on hyperparathyroidism secondary to uremia and summarize the advantages and disadvantages of both methods. METHODS: Uremic patients who received parathyroidectomy (PTX) in the last 3 years were divided into two groups according to the surgical methods used [subtotal parathyroidectomy (SPTX) group and total parathyroidectomy + autologous implantation (TPTX + AT) group]. TPTX was performed if less than 4 glands were found during surgery. The changes of various indexes after operation, and calculate the success rate and recurrence rate of patients were observed. The serum biochemical parameters were routinely monitored, the success rate, postoperative complications and recurrence were recorded. The patients were followed up. RESULTS: There were 20 patients in the SPTX group and 12 in the TPTX + AT group. The success rate of surgery was 85% and 91.7% in the SPTX group and TPTX + AT group, respectively, among 32 patients included for final analysis. The mean PTH and postoperative ALP in the TPTX + AT group were slightly lower than in the SPTX group, except for the PTH levels at 6 months after surgery (P<0.05). The incidence of postoperative hypocalcemia was 100% in both groups. The incidence of wound infection in the two groups was 0% and 16.7% in the SPTX group and TPTX + AT group, respectively. The mean calcium supplementation in the TPTX + AT group was significantly more than in the SPTX group within 1 year after surgery. The mean postoperative bone mineral density in the SPTX group was significantly higher than in the TPTX + AT group. The time to postoperative remission of bone pain and muscle weakness was markedly shorter in the SPTX group than in the TPTX + AT group. The post-operative quality of life (QOL) in the SPTX group was significantly better than in the TPTX + AT group. CONCLUSIONS: These findings suggest that SPTX achieves a better short-term efficacy, but TPTX + AT has a better long-term efficacy. Therefore, the selection of surgical method for PTX may be based on the age, estimated survival time and possibility of kidney transplantation.

Parathyromatosis type 2 detected by 99mTc-MIBI SPECT/CT.

Parathyromatosis, which is defined as multiple foci of benign hyperfunctioning parathyroid tissue in neck or mediastinum, is a rare but severe cause of persistent/recurrent renal hyperparathyroidism (rHPT) after parathyroidectomy (PTX). It is hard to detect and remove all the foci. We present a case of parathyromatosis in a haemodialysed patient, who had three PTXs for persistent/recurrent rHPT and was free of recurrence during 31-month follow-up after the third PTX. 99mTc-MIBI SPECT/CT scan prior to the third PTX located all the lesions. The presented case suggests that preoperative 99mTc-MIBI SPECT/CT is useful for successful surgical removal of parathyromatosis.

Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy.

Parathyroid cells release parathyroid hormone (PTH), which controls calcium homeostasis. Loss of parathyroid cells results in hypoparathyroidism and consequent low-turnover bone disease. Here, we investigated whether our recently-established human tonsil-derived mesenchymal stem cells (TMSC) restore in vivo parathyroid cell function in rats with parathyroidectomy (PTX). Compared with undifferentiated control TMSC, TMSC differentiated with activin A and soluble sonic hedgehog induced a significant release of PTH as early as day 7, with increased PTH release occurring in response to lower calcium levels and vice versa. Released PTH increased osteocalcin expression and alizarin red S staining in preosteoblastic cells, indicating its functional activity. PTX rats fed calcium-free diet only survived for ∼10 days. Subcutaneous injection with TMSC alone did not increase their survival rates, regardless of differentiation. However, survival rates increased for up to 28 days in response to TMSC embedded in Matrigel (TMSC-MA), showing 40% and 80% in control and differentiated TMSC-MA, respectively. When compared with continuous increases by control TMSC-MA, stable levels of secreted PTH and serum ionized calcium were found in PTX rats with differentiated TMSC-MA. This is the first report that differentiated TMSC resemble parathyroid cells and, if embedded in Matrigel, restore in vivo parathyroid function.

Young age, male sex, and end-stage renal disease with secondary hyperparathyroidism as risk factors for intraoperative hyperkalemia during parathyroidectomy.

STUDY OBJECTIVE: The aim of this study was to investigate the risk factors of intraoperative hyperkalemia in end-stage renal disease patients undergoing parathyroidectomy (PTx) with autotransplantation (AT). DESIGN: Prospective observational study. SETTING: Operating room of a tertiary care medical center. PATIENTS: Thirty-two adult, American Society of Anesthesiologists physical status 2 and 3 patients with secondary hyperparathyroidism aged between 31 and 72 years scheduled for PTx with AT. MEASUREMENTS: Laboratory chemistries (intact parathyroid hormone, Na, K, Ca, P, arterial blood gas) were obtained before surgery and at 2 time points during surgery. The first chemistry levels during surgery were checked after the first 2 parathyroid glands had been removed, and the second levels were checked after wound closure. Statistical analysis was performed using t test, Fisher exact test, the receiver operating characteristic curve method, as appropriate. MAIN RESULTS: Eight patients (25%) developed hyperkalemia during surgery. The hyperkalemia patients had younger age (42±11.44 years vs 52.58±11.83 years, P=.044) and a male dominance (odds ratio, 11.4; P=.01; 95% confidence interval, 1.74-74.65). The cutoff for age was 40.5 years, according to the highest value for sensitivity plus specificity of the receiver operating characteristic curve. There was a higher incidence of intraoperative hyperkalemia in younger patients than in older patients (odds ratio, 8.33; P=.023; 95% confidence interval, 1.39-49.87) as well as a significant increase in potassium level during surgery in younger male patients (P=.005 and .002, respectively). CONCLUSIONS: The anesthesiologist should be aware of the complications of intraoperative hyperkalemia during PTx with AT, especially in male end-stage renal disease patients younger than 40 years.

Percutaneous ethanol injection therapy for advanced renal hyperparathyroidism in Japan: 2004 survey by the Japanese Society for Parathyroid Intervention.

Background. Marked hyperplasia of the parathyroid gland (PTG) is a characteristic feature of severe hyperparathyroidism in patients under chronic haemodialysis treatment. Percutaneous ethanol injection therapy (PEIT) is now becoming popular in Japan as a treatment option for secondary hyperparathyroidism (SHPT) and its cost is covered by the National Health Insurance (NHI) System. The Japanese Society for Parathyroid Intervention surveyed its membership in 2004 to revise the guidelines for the use of PEIT. Methods. The project was approved by the Executive Committee of the Society, and the primary questionnaire was addressed to 3268 centres (departments) affiliated with the Japanese Society for Dialysis Therapy. A follow-up questionnaire was sent to all the centres that responded. Results. Although the number of centres to which the questionnaire was sent in 2004 was 3268, compared with 2653 in 1998, the number of responses decreased from 1425 (53.7%) in 1998 to 962 (29.4%) in 2004. To the question of whether the centre performed PEIT, 114 (11.9%) answered 'Yes' and 848 (88.1%) answered 'No' in 2004. It was an increase from 1998 when only 83 (5.8%) of 1425 centres answered 'Yes'. In the 1998 survey, 612 patients underwent PEIT at 74 centres, and in 2004, 2098 patients underwent PEIT at 111 centres. Conclusions. PEIT may become the frequently performed treatment for SHPT patients who become resistant to medical therapy. However, the same problems as in 1998 remain unsolved; that is, recurrent nerve paralysis, difficulty of post-PEIT PTx and lack of evidence showing the long-term effectiveness of PEIT.