Dynamics of skeletal resistance to parathyroid hormone in the rat: effect of renal failure and dietary phosphorus

Bover, Jordi; Jara, Aquiles; Trinidad, Pedro; Rodriguez, Mariano; Felsenfeld, Arnold J.

doi:10.1016/s8756-3282(99)00169-6

Cited by 45 publications

(28 citation statements)

References 27 publications

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“…Many previous studies have shown that phosphate loading or hyperphosphatemia induces skeletal resistance to parathyroid hormone (PTH) and, as a result, PTH secretion is stimulated [1, 2, 3, 4]. Recent in vitro and in vivo studies have shown that a high phosphate concentration directly stimulates PTH secretion and prevents appropriate PTH suppression in a high calcium concentration [5, 6, 7, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

“…Besides its hypercalcemic effect, calcitriol also decreases PTH mRNA transcription [11]. Failure to control hyperphosphatemia in dialysis patients is associated with a poor response to calcitriol treatment [12], but it is unclear whether the poor response results from a direct stimulatory effect of phosphate on PTH secretion [5, 6, 7, 8]or increased skeletal resistance to PTH [1, 2, 3, 4]. In the former, phosphate may act at a post-transcriptional site to increase the stability of the PTH mRNA transcript [13].…”

Section: Introductionmentioning

confidence: 99%

“…In the former, phosphate may act at a post-transcriptional site to increase the stability of the PTH mRNA transcript [13]. In the latter, a decreased calcemic response to PTH results in the need for more PTH to maintain the same serum calcium value [4], an effect which presumably would increase PTH mRNA transcription. Our goal was to determine whether hyperphosphatemia affected the capacity of calcitriol-induced hypercalcemia to suppress PTH secretion in sham-operated and 5/6 nephrectomized rats with hyperparathyroidism.…”

Section: Introductionmentioning

confidence: 99%

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Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats

Jara

Chacón

Felsenfeld

2002

Nephron

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Background/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. Methods: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1 – normal renal function (NRF) + 0.6% P + vehicle; group 2 – NRF + 0.6% P + CTR; group 3 – renal failure (RF) + 0.6% P + vehicle; group 4 – RF + 1.2% P + CTR; and group 5 – RF + 0.6% P + CTR. Results: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 ± 0.26 and 15.12 ± 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = –0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). Conclusions: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats

Jara

Chacón

Felsenfeld

2002

Nephron

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“…However, these findings suggest that such high levels may not be required in cases of mild renal insufficiency or normal renal allograft function such as those described here. Since it has been shown that elevated serum phosphorus levels may contribute to bone resistance to PTH, the post-transplant decrease in phosphorus could help normalize the bone response to this hormone (15).…”

Section: Discussionmentioning

confidence: 99%

Improvement of adynamic bone disease after renal transplantation

Abdallah

Jorgetti

Pereira

et al. 2006

Braz J Med Biol Res

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Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

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“…[31,[34][35][36] It has been shown that dietary P restriction totally prevents uremia-induced parathyroid cell growth and ameliorates secondary hyperparathyroidism in uremic dogs [37] and rats. [38] Feeding the HPD resulted in hyperphosphatemia and hypocalcemia 12 weeks post-surgery in CRF rats compared to sham-operated controls receiving the same diet.…”

Section: Tablementioning

confidence: 99%

Role of Dietary Phosphorus and Degree of Uremia in the Development of Renal Bone Disease in Rats

et al. 2007

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The remnant kidney rat model has been extensively used for the evaluation of bone changes due to uremia. The present study aimed to assess the effect of the dietary phosphorus availability and of the severity of renal failure on bone histomorphometric changes and various biochemical markers over time in this model. Chronic renal failure (CRF) was induced in male Wistar rats by 5/6 th nephrectomy. Half of the number of animals received a standard rat diet (STD) (0.67% P, containing low bioavailable phosphorus of plant origin); the other animals were fed a high phosphorus diet (HPD) (0.93% P, containing inorganic phosphorus with high bioavailability). Every two weeks, blood and urine samples were collected. At sacrifice after 6 or 12 weeks, bone samples were taken for the measurement of histological and histodynamic parameters. Serum creatinine measurements indicated the development of mild to moderate renal failure in both diet groups. Phosphaturia was unexpectedly low in all animals that received the STD, indicating relative phosphorus depletion despite the normal dietary phosphorus content. In the HPD CRF group, a decrease in calcemia and a rise in phosphatemia were seen after 12 weeks of CRF, which were more pronounced in animals with higher serum creatinine. Serum iPTH levels were distinctly increased in CRF rats fed a HPD, especially those with more pronounced renal failure. Serum osteocalcin and to a lesser extend tartrate-resistant acid phosphatase and urinary pyridinoline and deoxypyridinoline crosslinks were higher in the CRF animals compared to the shams, particularly in the animals of the HPD group with more pronounced CRF. In both diet groups, the CRF animals had significantly higher amounts of osteoid compared to shams. Only the animals that received a HPD developed distinct histological signs of secondary hyperparathyroidism (sHPTH), that is, an increased bone formation rate, mineral apposition rate, osteoblast perimeter, and eroded perimeter. Again, this effect was most prominent in rats with more severe CRF. In conclusion, data of the present study indicate that in experimental studies using the remnant kidney rat model, both the dietary phosphorus bioavailability and the degree of renal failure in the development of hyperparathyroidism should be considered.

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Dynamics of skeletal resistance to parathyroid hormone in the rat: effect of renal failure and dietary phosphorus

Cited by 45 publications

References 27 publications

Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats

Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats

Improvement of adynamic bone disease after renal transplantation

Role of Dietary Phosphorus and Degree of Uremia in the Development of Renal Bone Disease in Rats

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