Original InvestigationsIncreased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure*,**,*,**
Section snippets
Serum samples
For the pilot study, serum samples were obtained from chronic dialysis patients at facilities affiliated with Niigata University (Niigata, Japan) and Kobe University (Kobe, Japan; n = 162; 108 men, 54 women; age, 55.71 ± 28.45 years) and age- and sex-matched healthy volunteers (n = 212; 130 men, 82 women; age, 53.45 ± 26.87 years) with creatinine levels less than 1.0 mg/dL and no abnormal urinalysis findings.
For the main study, serum samples were obtained from 46 predialysis patients (26 men,
Results
In healthy controls, serum OCIF levels were similar (0.945 ± 0.263 ng/mL) to those reported previously16 and increased in an age-dependent manner (OCIF = 0.226 + 0.020 × age; r2 = 0.529; P < 0.0001). Age-dependent increases in serum OCIF levels also were observed in age- and sex-matched dialysis patients (OCIF = 0.121 + 0.051 × age; r2 = 0.126; P < 0.0001), as well as healthy controls. However, OCIF levels in dialysis patients were higher than those of healthy controls for all ages (Fig
Discussion
The calcemic action of PTH is blocked in uremic patients, referred to as increased skeletal resistance to PTH.1 Bone histomorphometric studies have shown that parameters associated with osteoclastic bone resorption generally were suppressed compared with values estimated from serum PTH levels in healthy controls.3, 17, 18, 19, 20, 21 Because increased skeletal resistance to PTH was first recognized in the early 1970s, it has been regarded as one of the major mechanisms of pathogenesis of
Acknowledgements
The authors thank Dr Takeshi Kurosawa, Sumiyoshi Clinic Hospital, Mito, Japan, for cooperation in serum sampling from chronic dialysis patients. We also thank members of the ROD-21 Clinical Research Group for thoughtful discussions.
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Cited by (156)
The role of osteoprotegerin (OPG) in fibrosis: its potential as a biomarker and/or biological target for the treatment of fibrotic diseases
2021, Pharmacology and TherapeuticsCitation Excerpt :These cytokines and growth factors activate (myo)fibroblasts and promote interstitial fibrosis (X.-M. Meng, Nikolic-Paterson, & Lan, 2014). High serum OPG levels were observed in patients with chronic kidney disease receiving haemodialysis (Kazama et al., 2002). Furthermore, elevated serum OPG was found to predict decline of kidney function in elderly women (Lewis et al., 2014).
Osteoprotegerin Assessment Improves Prediction of Mortality in Stroke Patients
2019, Journal of Stroke and Cerebrovascular DiseasesEffect of uremic toxin-indoxyl sulfate on the skeletal system
2018, Clinica Chimica ActaCitation Excerpt :Therefore, IS could increase the cellular oxidative stress that may be a common disorder in the causal pathway between CKD and PTH hyporesponsiveness [39]. Osteoprotegerin (OPG), a decoy receptor of the osteoclast differentiation factor, has been reported to be considerably elevated in advanced CKD than in subjects with a normal kidney function [33, 40, 41]. Accumulation of serum OPG might block the actions of PTH on the bone [4].
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For the ROD-21 Clinical Research Group, Japan.
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Supported in part by a program project grant from the Ministry of Health, Japan (M.F.) and a Special Grant for Medical Research from the Ministry of Post and Telecommunications, Japan (M.F.).
- *
Address reprint requests to Masafumi Fukagawa, MD, PhD, Associate Professor and Chief, Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: [email protected]
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