Paricalcitol [19-nor-1,25-(OH)2D2] in the treatment of experimental renal bone disease.
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.


BACKGROUND
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.


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.
Jokihaara
Jarkko
J
Medical School and the Institute of Medical Technology, University of Tampere, Finland.
Pörsti
Ilkka
I
Pajamäki
Ilari
I
Vuohelainen
Tuomo
T
Jolma
Pasi
P
Kööbi
Peeter
P
Kalliovalkama
Jarkko
J
Niemelä
Onni
O
Kannus
Pekka
P
Sievänen
Harri
H
Järvinen
Teppo L N
TL
D000818:Animals; D001011:Aorta / Q000473:pathology; D001696:Biomechanical Phenomena; D015519:Bone Density; D001847:Bone Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002114:Calcinosis; D004872:Ergocalciferols / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D014057:Tomography, X-Ray Computed
D004872:Ergocalciferols; C084656:paricalcitol