Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats

Studies were carried out on male F344 rats to examine the influence of aging and life-prolonging food restriction on bone and circulating parathyroid hormone levels. In ad libitum fed animals, the weight, density and calcium content of the femur increased with age and achieved their peak levels by 12 months of age. These levels remained stable until about 24 months and by 27 months of age the ad libitum fed animals had lost appreciable amounts of bone. The maturation of the femurs of the animals maintained on 60% of the ad libitum food intake was delayed and their bones were lighter, less dense and contained less calcium than bones from ad libitum fed rats of corresponding ages. But at 6, 12 and 24 months of age, the femur strength to body weight ratios were very highly significantly greater (P < 0.0001) for the restricted animals compared to the ad libitum fed controls. Circulating immunoreactive parathyroid hormone increased progressively with aging in the animals fed ad libitum and the animals that experienced bone loss at advanced age also had the highest level of the hormone. In contrast, in the food restricted animals aging was not associated with a marked increase in serum parathyroid hormone or with senile bone loss. The data are discussed in relation to the mechanism of the observed changes.     

The effects of high dose of parathyroid hormone on fetal osteoclasts and their precursors in vivo: An ultrastructural-cytochemical study

Background: It is not well known how the immediate precursors of osteoclast develop into osteoclasts in the fetus. This ultrastructural-cytochemical study was designed to clarify the formation process of the osteoclasts and their increased activities in the fetal mouse limb buds after administration of high dose parathyroid hormone (PTH). Methods: Twenty-four or forty-eight hours after the high doses of PTH were injected into amniotic fluid of the pregnant C₃H mice, the femoral limb buds of embryos were dissected out. Tartrate-resistant acid phosphatase (TRAP) reactions were performed while preparing specimens for electron microscopy. Results: Both control and PTH-given preosteoclasts and osteoclasts exhibited TRAP-positivities in dense bodies and vesicles. As effects of PTH, a binucleated preosteoclast of tandem fashion was observed. More osteoclastic hyperactivities were observed in the diaphyseal bone marrow. An osteoclast with a large cytoplasm exhibited two sets of clear zones and ruffled borders. Some osteoclasts demonstrated prominent amoeboid figures, while other osteoclasts developed large cytoplasmic vacuoles, which contained pieces of calcified chondroid bars. Conclusions: Our results revealed the progression of maturation from young preosteoclasts to osteoclasts. An existence of a peculiar binucleated preosteoclasts suggested one of the processes for multinucleation of the osteoclast. Quite remarkable osteoclastic hyperactivities were obviously the effects of high dose PTH. Our results also indicated the endophagocytic ability of the osteoclast. How PTH affected the osteoclasts and their precursors in the diaphyseal bone marrow can be speculated. © 1995 Wiley-Liss, Inc.     

Fetal development in experimental uremia

Summary Uremic women on hemodialysis with metabolic bone disease (hyperparathyroidism, osteomalacia resulting from defective vitamin D metabolism) and anemia (erythropoietin deficiency) are known to give birth to infants without bone disease or anemia. Therefore, skeletal development (enchondral and desmal bone formation) and hepatic erythropoiesis were evaluated in fetuses of uremic rats. These fetuses failed to show defective mineralisation or evidence of bone disease. Bolus injection of high doses of exogenous PTH into the maternal or fetal organism did not affect fetal bone histology. In addition, no apparent defect of bone mineralisation or bone formation was found in fetuses of ricketic rats. Normal mineralisation in the offspring of uremic rats may be explained by fetal hyperphosphatemia and/or insensitivity of fetal (woven) bone mineralisation to vitamin D.Absence of fetal anemia (normal hematocrits, normal density of hematopoietic cells in the liver) in the presence of maternal anemia is presumably due to the insensitivity of fetal erythropoiesis to erythropoietin.With the support of Deutsche Forschungsgemeinschaft     

Evidence for interference of vitamin D with PTH/PTHrP receptor expression in opossum kidney cells

 Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats in vivo. The present study was undertaken to examine this interaction using monolayers of Opossum kidney (OK) cells. ³²P uptake, cAMP generation, PTH/PTHrP receptor mRNA expression and intracellular Ca²⁺ [Ca²⁺]_i were measured in (1) control cells, (2) cells exposed to PTH, (3) cells pretreated with 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and (4) 1,25(OH)₂D₃-pretreated cells exposed to PTH. ³²P uptakes were in (1) 5.00±0.20 (mean ±SE), in (2) 2.30±0.14 (P<0.001 versus group 1), in (3) 4.80±0.24 (P NS versus group 1) and in (4) 3.70±0.20 (P<0.001 versus group 2) nmol P_i/(mg·prot 10 mm). cAMP levels were in (1) 10±3, in (2) 210±8, in (3) 12±4, and in (4) 122±12 pmol cAMP/mg protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in relative units: (1) 100±0, (2) 99.5±6.2, (3) 68.7±2.6 (P<0.001 versus group 1), and (4) 34.8±3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced equal transient increments in [Ca²⁺]_i. These experiments demonstrate that the effect of vitamin D on phosphate transport is associated with a commensurate diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation but not with Ca²⁺ transients. Vitamin D per se does not affect ³²P uptake or cAMP generation while it slightly decreased PTH/PTHrP receptor gene expression. These observations demonstrate that: (1) 1.25(OH)₂D₃ directly antagonizes the effects of PTH on ³²P uptake in OK cells, (2) this effect is mediated via inhibition of PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP formation may stem at least in part from a decrease in the expression of PTH/PTHrP receptor mRNA. Received: 2 December 1997 / Received after revision: 19 January 1998 / Accepted: 28 January 1998     

Effects of saline loading on jejunal absorption of calcium,sodium, and water,and on parathyroid hormone secretion in the rat

Summary To investigate whether intestinal calcium absorption parallels that of sodium following extracellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium. sodium and water were studied in rats by perfusing jejunal loops in situ.After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using⁴⁵Ca, increased significantly (P<0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again, the b-l calcium flux increased but to a significantly lesser extent (P<0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P<0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone was unchanged after expansion with the calcium containing solution but increased following calcium-free infusion.It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree by calcium-free Ringer infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.     

慢性肾功能衰竭患者血清C—PTH变化与并发症的关系探讨

探讨慢性肾功能衰竭(CRF)患者血清羧基端甲状旁腺素(C-PTH)的变化及与钙磷代谢、高血压和贫血的关系。方法44例CRF患者用放免法测定血清C-PTH,血清尿素氮(BUN)、血清肌酐(Scr)、血清钙(Ca     

甲状旁腺肿瘤10例临床分析

目的 探讨甲状旁腺肿瘤的误诊原因,找出减少误诊的方法。方法 对1984－1998年我院收治的10例甲状旁腺肿瘤患者进行回顾性分析。结果 10例中8例患者临床表现为骨关节疾病和泌尿系结石,误诊率为80％。结论 临床医师应提高对该疾病的认识,对一些顽固的泌尿系结石和反复多次骨折的患者不仅要重视局部并发症的诊治,而且在考虑到诊断甲状旁腺肿瘤的可能性,并进行必要的血钙、血磷检测。     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.     

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004–2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21–73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8–3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.     

Acute biochemical variations induced by four different calcium salts in healthy male volunteers

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D₃ supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%;p<0.01) increases in Ca and significant suppression of PTH (–37.4% to –57.4%;p<0.01). Comparison of response curves revealed significantly (p<0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG and CC. No significant variation of iCT was recorded during the test. We conclude that all four Ca supplements seem to be absorbed to some extent since they induce significant biochemical variations that may lead to a reduction in bone turnover and that CC induces a significantly larger increase in serum Ca and a significantly greater suppression of serum PTH.