Increased Levels of Osteoprotegerin in Hemodialysis Patients

Avberšek-Lužnik, Ivica; Malešič, Ivan; Rus, Igor; Marc, Janja

doi:10.1515/cclm.2002.177

Cited by 41 publications

(26 citation statements)

References 16 publications

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“…According to our own and other's results, HD patients have higher OPG levels than their healthy controls. Also, the positive relationship between OPG and age found in normal individuals is maintained in end-stage renal disease [12]. At present, the mechanisms that regulate OPG secretion are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, they show that HD patients have higher OPG levels than healthy individuals; furthermore, OPG is not removed by HD and its levels are age-related, as in the normal population [11,12]. However, in individuals with chronic renal failure, no consistent correlations between OPG levels and PTH, Ca or phosphate have been found [13,14,15].…”

Section: Introductionmentioning

confidence: 94%

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Association between phosphate removal and markers of bone turnover in haemodialysis patients

Albalate¹,

Piedra²,

Fernández³

et al. 2006

Nephrology Dialysis Transplantation

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Background. As the main mineral reservoir, bone acts as a calcium (Ca) and phosphate buffering system. Accordingly, phosphate removal by haemodialysis (HD) might be theoretically influenced by bone turnover, as well as by the interaction of regulatory molecules, such as PTH and osteoprotegerin (OPG). The present study investigated the relationship between these variables and phosphate removal by HD. Methods. Blood samples for serum Ca, phosphate, bicarbonate, intact PTH, PTH (1-84), bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, OPG and receptor activator of nuclear factor-kB ligand (RANKL) were obtained in 28 HD patients. Phosphate removal was measured by a continuous collection of the dialysate. Results. Pre-dialysis serum phosphate concentration is the critical factor in determining dialytic phosphate removal. However, multiple regression analysis reveals that phosphate removal is better explained by a combination of factors than by phosphate concentration alone. In this model, the PTH/OPG ratio is an additional positive factor, whereas age and vitamin D treatment are negative factors. Patients with pre-HD bicarbonate higher than 20 mEq/l had higher serum phosphate and, accordingly, higher phosphate removal; of interest, these individuals also have significant differences in RANKL/OPG. Mean (SD) OPG levels were significantly higher than that in the healthy population (16.2 (12.5) pmol/l; these values correlated with age (r ¼ 0.4, P<0.04). Mean serum RANKL (1.03 (1.02) pmol/l) was within the range of normal individuals.Conclusions. Dialytic phosphate removal has a crucial, direct relationship with pre-HD plasma phosphate levels. However, the phenomenon of phosphate removal is more precisely explained using a more complex relationship, defined by the interaction between serum phosphate, PTH/OPG, age and vitamin D administration. Serum RANKL levels are first reported in HD patients, and are not different from the normal population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Association between phosphate removal and markers of bone turnover in haemodialysis patients

Albalate¹,

Piedra²,

Fernández³

et al. 2006

Nephrology Dialysis Transplantation

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“…Recent reports suggest that increased circulating OPG levels often occur in vascular calcification or cardiovascular disease. 11,13,53,54 Thus, circulating OPG levels were greater in postmenopausal women with a high rate of bone turnover (especially those with severe osteoporosis). 11,13,53 Serum OPG levels have correlated with bone resorption markers, serum calcium and PTH levels, and decreased bone mineral density, whereas they were inversely related to serum osteocalcin levels (a marker of bone formation) and unrelated to VD 3 levels.…”

Section: Relationships Between Serum Opg and Rankl Levels And Vasculamentioning

confidence: 99%

“…11 Elevated serum OPG levels have correlated with increasing age, diabetes, hypertension, increased cardiovascular mortality, the presence and severity of coronary artery disease, and chronic renal failure. 11,13,[53][54][55][56] Conversely, serum OPG levels declined in patients receiving glucocorticoid or immunosuppressive therapies. [57][58][59] Serum OPG levels may also be related to sex hormone levels because they were higher in women than men, diminished in postmenopausal women, increased by estrogen replacement therapy or oral contraceptives, and positively associated with bioavailable testosterone levels or, in some cases, estrogen levels.…”

Section: Relationships Between Serum Opg and Rankl Levels And Vasculamentioning

confidence: 99%

“…10 -13,62 However, serum OPG levels have also been positively associated or unrelated to PTH levels. 11,13,54,57,59 Generally, serum RANKL levels appear unaltered and unrelated to serum OPG levels, although they have sometimes declined as serum OPG levels increased. 11,13,29 Overall, these studies strongly indicate that serum OPG levels frequently rise in clinical conditions that favor atherosclerosis, vessel calcification, or vascular dysfunction, and they suggest OPG may have an important role in the cause or progression of vascular calcification.…”

Section: Relationships Between Serum Opg and Rankl Levels And Vasculamentioning

confidence: 99%

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Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin

Collin‐Osdoby

2004

Circulation Research

409

207

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Abstract-Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor B ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.

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Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis

Gonnelli

Montagnani

Caffarelli

et al. 2005

J Endocrinol Invest

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The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.

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Increased Levels of Osteoprotegerin in Hemodialysis Patients

Cited by 41 publications

References 16 publications

Association between phosphate removal and markers of bone turnover in haemodialysis patients

Association between phosphate removal and markers of bone turnover in haemodialysis patients

Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin

Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis

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