Relationships between OPG, RANKL, bone metabolism, and bone mineral density in biliary atresia

Honsawek, Sittisak; Chaiwatanarat, Tawatchai; Vejchapipat, Paisarn; Chongsrisawat, Voranush; Thawornsuk, Nutchanart; Poovorawan, Yong

doi:10.1007/s00383-009-2325-y

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…After 6 months, estrogen levels were significantly decreased, BMD was significantly decreased, and OPG levels were significantly increased. Other studies have suggested a similar compensatory mechanism in celiac disease (Fiore et al, 2006), anorexia nervosa (Ohwada et al, 2007), biliary atresia (Honsawek et al, 2009), fragility fractures in elderly women with low vitamin D status (Sypniewska et al, 2010), a patient on hemodialysis (Crisafulli et al, 2005), growth hormone deficiency (Flint et al, 2009), juvenile idiopathic arthritis (Masi et al, 2004), and in postmenopausal women with osteoporosis (Yano et al, 1999). …”

Section: Discussionmentioning

confidence: 91%

“…This hypothesis is based on other disease investigations involving patients without CIOF associated with breast cancer (summarized in Table 1). They suggest that as a transient, compensatory mechanism to counteract bone turnover and bone loss, OPG levels may rise (Crisafulli et al, 2005; Fiore et al, 2006; Flint et al, 2009; Honsawek et al, 2009; Masi et al, 2004; Ohwada et al, 2007; Sypniewska et al, 2010; Uemura et al, 2003; Yano et al, 1999). These studies collectively posit that early in CIOF development, decreases in estradiol lead to osteoclastogenesis, which causes increased bone resorption.…”

Section: Introductionmentioning

confidence: 99%

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Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

Oostra

Lustberg

Reinbolt

et al. 2015

Molecular and Cellular Endocrinology

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Purpose Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. Results Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions In what was likely a compensatory response to rapid bone loss, CIOF patients’ OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

Oostra

Lustberg

Reinbolt

et al. 2015

Molecular and Cellular Endocrinology

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“…Additionally, circulating leptin and osteoprotegerin levels has been shown to be correlated with BMD and the presence of jaundice in BA, suggesting that leptin and osteoprotegerin could play a pontential role in maintaining bone mass of BA patients[12,13]. …”

Section: Discussionmentioning

confidence: 99%

Low bone mineral density and the severity of cholestasis in biliary atresia

Homchan

Chaiwatanarat

Udomsinprasert

et al. 2017

WJH

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AIMTo investigate the prevalence of osteopenia and osteoporosis in postoperative biliary atresia (BA) children and the association of bone mineral density (BMD) and biochemical parameters in postKasai BA subjects.METHODSA total of 70 patients with postKasai BA were enrolled in this prospective study. The patients were classified into two groups according to their jaundice status. BMD of the lumbar spine was analyzed using dual energy X-ray absorptiometry.RESULTSThe prevalence of low bone mass (osteopenia and osteoporosis) in BA patients were 51.4% (36 out of 70). Ten patients (35.7%) in the jaundice group and 8 patients (19.0%) in the non-jaundice group had osteopenia. Sixteen patients (57.1%) in the jaundice group and 2 patients (4.8%) in the no jaundice group had osteoporosis. In addition, lumbar spine BMD Z-score was substantially lower in the jaundice BA patients compared with non-jaundice patients. BA subjects with persistent jaundice had significantly lower serum 25-hydroxyvitamin D than those without jaundice. Further analysis revealed that lumbar spine BMD was correlated with age (r = 0.774, P < 0.001), serum albumin (r = 0.333, P = 0.005), total bilirubin (r = -0.476, P < 0.001), aspartate aminotransferase (r = -0.583, P < 0.001), alanine aminotransferase (r = -0.428, P < 0.001), and alkaline phosphatase(r = -0.456, P < 0.001).CONCLUSIONLow BMD was associated with biochemical parameters reflecting the severity of cholestasis in postKasai BA patients.

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“…OPG acts by neutralizing RANKL, an essential cytokine required for osteoclast formation and activation [1]. Prior studies have showed that OPG is not only an important regulatory factor of bone growth, bone modeling, and bone remodeling [2, 3], but also an intermediary factor of a wide variety of hormones, cytokine, and growth factors which are involved in regulating bone metabolism [4]. In vitro, osteoclast differentiation which is induced by 1,25-(OH) 2 D 3 , PTH, PGE 2 , and IL-4 is blocked by OPG in a dose-dependent manner [5, 6]; in vivo, recombinant OPG increases significantly bone mass and bone mineral density of lumbar spine and femoral of ovariectomized rat [7].…”

Section: Introductionmentioning

confidence: 99%

Establishment of OPG Transgenic Mice and the Effect of OPG on Bone Microarchitecture

Liu

Guo

et al. 2013

International Journal of Endocrinology

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Osteoprotegerin (OPG) plays a determinant role in regulating bone metabolism, but the effect of OPG on bone microarchitecture needs to be further elucidated. We attempted to construct pCI-hOPGp-mOPG vector containing human OPG promoter and FLAG tag and to microinject vector into fertilized zygotes from C57BL/6J × CBA mice to prepare transgenic mice. The OPG transgenic positive mice were identified by PCR and western blotting. Twelve-week-old OPG transgenic mice (OPG-Tg mice) and wild-type mice (WT mice) were utilized in the study of bone microarchitecture. Microcomputed tomography (micro-CT) data showed that compared with WT mice, the tibia of OPG-Tg mice showed an increased volumetric BMD (vBMD), tissue BMD (tBMD), trabecular thickness (Tb.Th), and trabecular number (Tb.N), and a decreased trabecular separation (Th.Sp) (P < 0.05) . The cortical bone microarchitecture parameters, such as cortical area (Ct.Ar), cortical thickness (Ct.Th), cortical BMD (Ct.BMD), cortical BMC (Ct.BMC), BMD, and BMC of femur, were increased, and the inner perimeter (In.Pm) was decreased, in OPG-Tg mice, compared to those in WT mice (P < 0.05). The established OPG transgenic mouse model could be valuable for further studying the biological significance and gene regulation of OPG in vivo.

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Relationships between OPG, RANKL, bone metabolism, and bone mineral density in biliary atresia

Abstract: Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss.

Cited by 5 publications

References 29 publications

Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

Low bone mineral density and the severity of cholestasis in biliary atresia

Establishment of OPG Transgenic Mice and the Effect of OPG on Bone Microarchitecture

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