Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.     

继发性甲状旁腺功能亢进患者甲状旁腺切除术后重度低钙血症相关因素分析

目的：探讨继发性甲状旁腺功能亢进（SHPT）患者甲状旁腺切除术后重度低钙血症（SHC）相关因素,进而建立SHC防治策略。方法回顾性分析2012年3月—2014年5月在我院行甲状旁腺切除治疗的S H P T病例资料。行单因素及多因素分析明确S HC的独立影响因素,确定定量因素界值。结果共收集88例病例资料,术后发生S HC46例（52.3％）。单因素分析显示年龄、ALP、iPTH、切除的甲状旁腺数（RTPN）具有统计学显著差异,多因素分析显示年龄、iPTH、RTPN≥4为SHC的独立影响因素,确定的界值为年龄48岁（PPV68.8％,NPV67.5％）和iPT H 1750 pg／ml（PPV85.4％,NPV87.5％）。结论年龄、甲状旁腺激素水平、甲状旁腺切除数量为SHPT患者甲状旁腺切除术后SHC的独立影响因素。选择性地对高危患者实施静脉补钙,选择合理的手术方式,可作为防治S HC的初步策略。     

Giant Cell Lesions Associated with Primary Hyperparathyroidism

Aims and Objective

To evaluate the prevalence, clinical features, diagnostic laboratory values and treatment outcome of giant cell lesions (brown tumors) associated with primary hyperparathyroidism (PHPT) in oral and maxillofacial region.

Study Design

A 5 year retrospective data was analyzed wherein all histopathologically proven cases of giant cell lesions involving oral and maxillofacial region were evaluated. Out of these cases, those associated with PHPT were tabulated. Correlation was established with other concomitant clinical features and also with the laboratory values of altered serum calcium, phosphate, alkaline phosphate and parathormone. Follow up of these cases after the correction of PHPT was also noted.

Result

Out of 85 cases of histopathologically proven giant cell lesions, five cases were associated with PHPT. There was involvement of maxilla and mandible in one case each. Only frontal bone was involved in two cases. Fifth case had multiple lytic lesions in maxilla and frontal bone. All patients consistently showed very high values of alkaline phosphate and parathormone. Hypercalcemia and hypophosphatemia was noted in four cases. All cases showed regression of the lytic lesion after parathyroidectomy obviating the need for surgical excision of the jaw lesions.

Conclusion

Giant cell lesions (brown tumors) associated with PHPT in oral and maxillofacial region are rare clinical entities. The prevalence of PHPT associated giant cell lesions is 5.9 %. They are clinically, radiologically and histopathologically similar to any other peripheral or central giant cell tumor. Relevant history may alert the clinician and altered biochemical values may help in correlating the oral and maxillofacial findings with the underlying systemic disease. At times, the brown tumor maybe the only presenting sign leading to the diagnosis of PHPT.     

以骨损伤为主要表现的原发性甲状旁腺功能亢进症误诊一例

报道1例原发性甲状旁腺功能亢进症误诊病例。患者是以多发骨痛为临床表现的绝经后女性,因多发骨骼病变被误诊为原发性骨质疏松、骨髓瘤、骨转移瘤等。本文旨在警示临床医师关注骨质疏松的诊断与鉴别诊断,减少并避免误诊、误治。     

射频消融术(RFA)治疗继发性甲状旁腺功能亢进(SHPT)的安全性及有效性分析

目的 探讨超声引导下射频消融术治疗慢性肾脏病（chronic kidney disease,CKD）继发性甲状旁腺功能亢进（secondary hyperparathyroidism,SHPT）的安全性及有效性。方法 选取复旦大学附属中山医院2017年10月至2018年9月确诊为SHPT并进行超声引导下射频消融术（radiofrequency ablatio,RFA）的患者15例,共15枚甲状旁腺增生结节,以超声造影作为测量消融术前后甲状旁腺结节大小的标准方法。对比消融术前后甲状旁腺结节大小、甲状旁腺激素（parathyroid hormone,PTH）、血钙（Ca）、血磷（P）、碱性磷酸酶（alkaline phosphatase,ALP）、活性维生素D[1,25-（OH）₂D]、临床症状（骨痛、皮肤瘙痒、失眠、手抖）及并发症情况。结果 与消融术前比较,患者术后1、3和6个月甲状旁腺结节明显变小（P<0.05）,结节缩小率分别为66%、93%和98%,术后1天、1、3和6个月血清PTH、Ca、P、ALP水平明显下降（P<0.05）,活性维生素D水平无明显改变,患者的临床症状明显好转。并发症声音嘶哑的发生率为6.7%,低钙血症的发生率6.7%,治疗后均恢复,且未再复发,无其他并发症。结论 超声引导下经皮RFA治疗SHPT安全有效,能明显改善患者症状,且并发症较少。     

The relationship between vitamin D and PTH levels and cardiovascular risk in the elderly hypertensives

Introduction and objective: In this study, we aimed to investigate the relationship between vitamin D, parathyroid hormone (PTH) and cardiovascular risk (CVR) in hypertensive patients aged 65 years and over.

Patients and methods: This study was performed with 84 hypertensive patients and 68 normotensive control group in Afyon Kocatepe University Faculty of Medicine Hospital. The determined cardiovascular risk degrees and the stages of blood pressure were compared with the levels of 25-(OH) vitamin D and PTH.

Results: Mean systolic and diastolic blood pressure (BP) levels of the patients with vitamin D deficiency (VDD) were significantly higher than those without VDD (p?hyperparathyroidism were significantly higher than those without hyperparathyroidism (p?=?0.012, p?=?0.036, respectively). CVR was reversely correlated with vitamin D but the correlation with hyperparathyroidism did not reach statistically significant level (r?=?–0.752, p?r?=?0.210, p?=?0.055), respectively.

Conclusion: These results indicate that the presence of hypertension is associated with VDD, as well as the stage of hypertension contributes to insufficiency, hyperparathyroidism and increased CVR. Clinicians should be aware and perhaps more aggressive for the treatment of HT and VDD in patients over 65 years of age.     

Clinical Benefit of the Change of Dialysate Calcium Concentration From 3.0 to 2.75 mEq/L

Because active vitamin D preparations and calcimimetics have been widely used to treat secondary hyperparathyroidism, maintenance of acceptable serum calcium and phosphate levels is important. A 2.75 mEq/L dialysate calcium product, which may bring the calcium balance closer to 0, has recently been launched, and we had an opportunity to examine its possible benefits. We performed a 6‐month retrospective review after switching from 3.0 mEq/L to 2.75 mEq/L calcium dialysate in 85 outpatients undergoing chronic hemodialysis. We evaluated blood biochemical parameters, including predialysis and postdialysis serum calcium and phosphate levels, predialysis intact parathyroid hormone (iPTH) levels; dialysis dose (Kt/V); and doses of concomitant active vitamin D preparations, calcimimetics, phosphate binder, and erythropoiesis‐stimulating agents. Postdialysis calcium levels were significantly lower and predialysis corrected calcium levels significantly decreased. The change in calcium levels before and after dialysis was smaller after switching of the dialysate than before. iPTH levels significantly increased 1 month after switching of the dialysate. No remarkable changes were observed in phosphate levels or Kt/V. The dose of alfacalcidol, one of the concomitant drugs, somewhat increased, and no remarkable changes in dosage were observed for other concomitant drugs. These results were favorable in terms of calcium balance. However, there may be limitations in interpreting the results, but the resultant calcium levels suggest that switching to 2.75 mEq/L calcium dialysate may improve the control of calcium levels. In addition, it is hoped that the treatment choice of secondary hyperparathyroidism is extended.     

Control of bone resorption in mice by Schnurri-3

Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.