Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease.
Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.
INSERM Unit 1088, UFR de Médecine et Pharmacie, Picardie University Jules Verne (UPJV), 1, Rue des Louvels, bat A, 3ème, 80037, Amiens Cedex, France.
Fellype C
FC
Barreto
Rodrigo B
RB
de Oliveira
Joyce
J
Benchitrit
Loïc
L
Louvet
Raja
R
Rezg
Sabrina
S
Poirot
Vanda
V
Jorgetti
Tilman B
TB
Drüeke
Bruce L
BL
Riser
Ziad A
ZA
Massy
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D015314:Dialysis Solutions / Q000494:pharmacology*; D011756:Diphosphates / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061205:Vascular Calcification / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D001057:Apolipoproteins E; D015314:Dialysis Solutions; D011756:Diphosphates; C107241:diphosphoric acid