Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications for post-transplantation bone disease

Westenfeld, Ralf; Schlieper, Georg; Wöltje, Michael; Gawlik, Alexander; Brandenburg, Vincent; Rutkowski, Przemysław; Floege, Jürgen; Jahnen-Dechent, Willi; Ketteler, Markus

doi:10.1093/ndt/gfr214

Cited by 75 publications

(51 citation statements)

References 39 publications

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“…So we concluded that TAC could induce bone disorders in kidney transplant recipients and accelerate bone resorption. Our results were in agreement with a recent study from Westenfeld et al [21]. The possible mechanism of TAC on bone mainly due to the resorption exceeded formation involving the imbalance of RANK-RANKL-OPG system [9,21] or partly by inhibiting ERK 1/2 [8].…”

Section: Discussionsupporting

confidence: 94%

Impact of tacrolimus on bone metabolism after kidney transplantation

Luo

Shi

Bai

et al. 2012

International Immunopharmacology

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Section: Discussionsupporting

confidence: 94%

Impact of tacrolimus on bone metabolism after kidney transplantation

Luo

Shi

Bai

et al. 2012

International Immunopharmacology

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“…Steroids directly worsen bone formation by impaired genesis and increased apoptosis of osteoblasts and enhanced osteoclastogenesis through an increased RANKL/OPG ratio [30] . Both cyclosporin and tacrolimus similarly promote bone loss via direct osteoclast activation [58] , but sirolimus is administered as a bone-sparing immunosuppressive agent due to its capability to inhibit osteoclast generation [57,59] .…”

Section: Ptbd: Epidemiology and Mechanismsmentioning

confidence: 99%

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Cianciolo¹,

Galassi

Capelli³

et al. 2016

Am J Nephrol

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction. Fibroblast growth factor-23-parathyroid hormone (PTH)-vitamin D axis, immunosuppressive therapy and previous bone status have been associated with PTBD. Although several studies reported reduced PTH levels in KTRs receiving nutritional vitamin D, its effects on bone mineral density (BMD) remain controversial. Active vitamin D reduced PTH levels and increased BMD after transplantation, but paricalcitol treatment was not accompanied by benefits on osteopenia. Vitamin D is considered protective against CVD due to the widespread pleiotropic effects, but data among KTRs remain scanty. Although vitamin deficiency is associated with lower glomerular filtration rate (GFR) and faster estimated GFR decline and data on the anti-proteinuric effects of vitamin D receptor activation (VDRA) in KTRs sound encouraging, reports on related improvement on graft survival are still lacking. Clinical data support the efficacy of VDRA against HPTH and show promising evidence of VDRA's effect in counteracting post-transplant proteinuria. New insights are mandatory to establish if the improvement of surrogate outcomes will translate into better patient and graft outcome.

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“…Some studies suggest a relationship between VC and impaired bone metabolism as well as an involvement of immunosuppressive drugs on expression, regulation, and function of RANKL, RANK, and OPG system working in skeletal and vascular systems. In particular, sirolimus inhibits osteoclast formation, unlike steroids and cyclosporine [56]. …”

Section: Progression Risk Factorsmentioning

confidence: 99%

Importance of Vascular Calcification in Kidney Transplant Recipients

Cianciolo¹,

Capelli²,

Angelini³

et al. 2014

Am J Nephrol

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Background: Kidney transplantation is the treatment of choice for chronic kidney disease (CKD), but in kidney transplant recipients (KTRs) cardiovascular events are the first cause of death with a functioning graft, ranging from 36 to 55%. The impact of vascular calcification (VC) on morbidity and mortality of KTRs is not appreciated enough nowadays. Summary: This review summarizes 13 important studies on VC in KTRs, comparing the results with CKD and dialysis populations. We focused on VC evaluation and use of coronary artery calcification (CAC) and aorta calcification (AoC) scores. We also evaluated the influence of traditional and non-traditional progression risk factors. Key Messages: VC strongly predicts cardiovascular events and all-cause mortality in KTRs. VC assessment is important in KTRs and based essentially on multislice computed tomography or electron beam computed tomography recognition of lesions. Quantitative measurement of CAC and AoC scores is essential for a correct definition of the calcium burden before and after kidney transplant. Progression of CAC slows down but does not halt after kidney transplant. A variable association of both traditional and non-traditional risk factors is shown. There is a strong association between baseline CAC score and CAC progression. A significant improvement in secondary hyperparathyroidism after transplantation favorably affects the progression of CAC. Low 25(OH)D₃ levels are an independent determinant of CAC progression. Diabetes is a risk factor for the presence of CAC in KTRs, but has not been independently associated with CAC progression. The data published on the use of immunosuppressive drugs as progression factors are few and inconclusive.

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Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications for post-transplantation bone disease

Abstract: Taken together, SRL was shown to inhibit osteoclast formation in vivo and in vitro. SRL thus may have the potential to balance osteoclast promoting effects of glucocorticoids and CI, thereby counteracting the development of accelerated osteoporosis in renal transplant recipients.

Cited by 75 publications

References 39 publications

Impact of tacrolimus on bone metabolism after kidney transplantation

Impact of tacrolimus on bone metabolism after kidney transplantation

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Importance of Vascular Calcification in Kidney Transplant Recipients

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