Vitamin D3 analogs and salmon calcitonin partially reverse the development of renal osteodystrophy in rats

Jablonski, Greg Eigner; Mortensen, Berit; Klem, K H; Mosekilde, Leif; Danielsen, C. C.; Gordeladze, Jan O.

doi:10.1007/bf00302075

Cited by 15 publications

(7 citation statements)

References 37 publications

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“…Although the objective of this study was to examine the effectiveness of paricalcitol in the prevention/treatment of renal insufficiency-induced changes in bone structure, it would have been interesting to compare the effect of this (24) In addition, the lower calcemic and phosphatemic activities of paricalcitol, caused by the lower stimulation of intestinal calcium and phosphate absorption, (25) and lower stimulation of bone resorption, (22) (27) The whole picture is far from clear, because active 1,25 vitamin D levels have been reported to inversely correlate with the extent of calcification in human coronary arteries. (28) At present, hyperphosphatemia is known to be a highly significant risk factor for soft tissue calcification in chronic renal insufficiency.…”

Section: Discussionmentioning

confidence: 99%

“…However, the beneficial effect of 1,25(OH) 2 D 3 has already been shown in the treatment of bone disease in experimental renal insufficiency, in a corresponding secondary prevention setting like our study. (24) In addition, the lower calcemic and phosphatemic activities of paricalcitol, caused by the lower stimulation of intestinal calcium and phosphate absorption, (25) and lower stimulation of bone resorption, (22) make it difficult to adequately compare the effects of paricalcitol and 1,25(OH) 2 D 3 on bone. Multiple doses of each agent would be required, because the comparison should be performed at corresponding effects on PTH, at corresponding effects on phosphate and calcium, and at corresponding doses in absolute quantity to examine direct effects on bone.…”

Section: Discussionmentioning

confidence: 99%

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Paricalcitol [19-Nor-1,25-(OH)2D2] in the Treatment of Experimental Renal Bone Disease

Jokihaara

Pörsti

Pajamäki

et al. 2006

Journal of Bone and Mineral Research

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Paricalcitol is a less hypercalcemic vitamin D analog that has been shown to suppress secondary hyperparathyroidism and to prevent the associated histomorphometric changes in bone. In this study, we show that paricalcitol also ameliorates the renal insufficiency-induced loss of bone mineral and the mechanical competence of bone.Introduction: Renal bone disease is a common consequence of chronic renal insufficiency and the associated secondary hyperparathyroidism (SH). Paricalcitol [19-nor-1,25(OH) 2 D 2 ] has been shown to ameliorate SH and prevent renal failure-induced histomorphometric changes in bone with minimal calcemic and phosphatemic activity. However, information about its efficacy on restoration of bone structural strength is lacking. In this study, we explored the effects of paricalcitol treatment on bone structure and strength in a model of advanced renal disease. Materials and Methods: Forty-five 8-week-old rats were randomly assigned to either surgical 5/6 nephrectomy (NTX) or Sham-operation. After a 15-week postoperative disease progression period, the NTX rats were further allocated to uremic control (NTX) and treatment (NTX + paricalcitol) groups, the latter of which received paricalcitol for the subsequent 12 weeks. After 27 weeks, the animals were killed, plasma samples were collected, and both femora were excised for comprehensive analysis of the femoral neck and midshaft (pQCT and biomechanical testing). Results: High mortality that exceeded 30% was observed in both NTX groups. NTX induced over a 13-fold increase in plasma PTH, whereas this increase was only 5-fold after paricalcitol treatment. At the femoral neck, NTX was associated with an 8.1% decrease (p < 0.05) in vBMD and a 16% decrease in breaking load (p < 0.05) compared with the Sham group, whereas paricalcitol treatment completely prevented these changes. At the femoral midshaft, the NTX resulted in a 6.6% decrease in cortical BMD (p < 0.01 versus Sham), and this change was also prevented by paricalcitol. Conclusions: Paricalcitol administration prevented renal insufficiency-associated decreases in BMD in the femoral neck and the femoral midshaft and restored bone strength in the femoral neck. Therefore, paricalcitol can efficiently ameliorate renal insufficiency-induced loss of bone mineral and mechanical competence of bone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Paricalcitol [19-Nor-1,25-(OH)2D2] in the Treatment of Experimental Renal Bone Disease

Jokihaara

Pörsti

Pajamäki

et al. 2006

Journal of Bone and Mineral Research

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“…Calcitriol administration was associated with a significant suppression of bone resorption and a marked increase in all osteoid parameters in the CRF condition 43 , 44 . The common marmoset has extremely high circulating levels of 1,25-(OH) 2 D 3 without exhibiting hypercalcemia 45 , 46 and has an abnormal 1,25-(OH) 2 D 3 receptor system, suggesting that the marmoset monkey has end-organ resistance to 1,25(OH) 2 D 3 .…”

Section: Discussionmentioning

confidence: 89%

Five-sixth Nephrectomy in Female Common Marmosets (<i>Callithrix jacchus</i>) as a Chronic Renal Failure Model

et al. 2014

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To assess the relevance and availability of subtotal nephrectomized common marmoset monkeys as a chronic renal failure (CRF) model, we observed for 26 weeks the pathophysiological condition of female marmosets subjected to five-sixth surgical nephrectomy (5/6Nx) by a two-step surgical method. The 5/6Nx marmosets showed a significant increase in serum levels of urea nitrogen, creatinine and cystatin-C immediately after 5/6Nx surgery. These renal disorder parameters subsequently tended to decrease with the passage of time but remained higher than the control levels by the end of the study. Hyperplastic parathyroid glands, a high turnover state of osteodystrophy in the femoral bone with higher serum ALP activity and anemia with hypocellularity of bone marrow were evident. The 5/6Nx marmosets showed a stable CRF condition for a long time and some characteristic disorders similar to those observed in CRF patients. These diagnostic aspects might be a species-specific anatomical and physiological signature, reflecting the nutritional condition. The CRF model using 5/6Nx marmosets might become a useful method of evaluating the unique mechanism of CRF development.

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“…[6] This model has been extensively used to assess pathophysiological aspects of CRF, [7][8][9][10][11] but is also the most frequently used model for the examination of bone changes due to uremia. [12][13][14][15][16][17][18][19] Strikingly, literature data indicate that with this model, varying degrees of secondary hyperparathyroidism are achieved, making comparisons between various studies and extrapolation to the human situation often difficult. The main reasons for this are the absence of standardization in duration and degree of renal failure and dietary phosphorus content/bioavailability between different studies.…”

Section: Introductionmentioning

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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Vitamin D3 analogs and salmon calcitonin partially reverse the development of renal osteodystrophy in rats

Cited by 15 publications

References 37 publications

Paricalcitol [19-Nor-1,25-(OH)2D2] in the Treatment of Experimental Renal Bone Disease

Paricalcitol [19-Nor-1,25-(OH)2D2] in the Treatment of Experimental Renal Bone Disease

Five-sixth Nephrectomy in Female Common Marmosets (<i>Callithrix jacchus</i>) as a Chronic Renal Failure Model

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

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