Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

Figures & data

Figure 1 Bone turnover through the OPG/RANK/RANKL pathway. The osteoclast precursor matures into a multinucleated cell under the influence of numerous factors such as cytokines, hormones, and growth factors. The multinucleated cell differentiates into an activated osteoclast in the presence of MCSF and RANKL. Once activated, the osteoclast starts degrading the bone surface, forming a lacuna. OPG, the decoy receptor of RANKL, inhibits the continuous binding of RANKL on RANK, therefore leading the osteoclast to its apoptosis. Thereafter, bone formation starts with preosteoblasts that have matured into osteoblasts in order to constitute new bone.

Table 1 Correlation between osteoprotegerin and different markers in women

	Women
	Correlation
	Positive	Absence	Negative
Aging	Kudlacek et al,^Citation21 Mazziotti et al,^Citation30 Pulsatelli et al,^Citation31 Nabipour et al,^Citation32 Oh et al,^Citation35 Mezquita-Raya et al,^Citation36 Khosla et al,^Citation40 Fahrleitner-Pammer et al,^Citation41 Indridason et al,^Citation42 Liu et al,^Citation43 Uemura et al^Citation50
Estradiol	Rogers et al^Citation39	Khosla et al^Citation40	Kudlacek et al^Citation21
Testosterone		Khosla et al^Citation40
PTH			Kudlacek et al^Citation21
BTMs	Mezquita-Raya et al^Citation36 (tALP, TRAP), Fahrleitner-Pammer et al,^Citation41 Indridason et al^Citation42 (OC), Liu et al^Citation43 (urinary NTx)	Nabipour et al,^Citation32 Han et al,^Citation37 Khosla et al^Citation40	Rogers et al,^Citation39 Indridason et al^Citation42 (TRAP)
BMD	Nabipour et al,^Citation32 Mezquita-Raya et al,^Citation36 Chiba et al,^Citation46 Stern et al^Citation47 (women with HRT)	Han et al,^Citation37 Rogers et al,^Citation39 Khosla et al,^Citation40 Indridason et al,^Citation42 Liu et al,^Citation43 Uemura et al^Citation50	Jorgensen et al^Citation45

Abbreviations: PTH, parathyroid hormone; BTM, bone turnover markers; tALP, total alkaline phosphatase; TRAP, tartrate-resistant acid phosphatase; OC, osteocalcin; NTx, cross-linked N-teleopeptide of type 1 collagen; BMD, bone mass density; HRT, hormone replacement therapy.

Table 2 Correlation between osteoprotegerin and different markers in men

	Men
	Correlation
	Positive	Negative
Aging	Kudlacek et al,^Citation21 Mazziotti et al,^Citation30 Pulsatelli et al,^Citation31 Khosla et al,^Citation40 Indridason et al,^Citation42 Szulc et al,^Citation52 Gannage-Yared et al^Citation53
Estradiol	Kudlacek et al,^Citation21 Szulc et al^Citation52	Khosla et al,^Citation40 Oh et al^Citation44
Testosterone	Oh et al,^Citation44 Szulc et al^Citation52	Khosla et al^Citation40
PTH		Kudlacek et al,^Citation21 Szulc et al^Citation52
BTM	Khosla et al,^Citation40 Indridason et al^Citation42(OC)	Oh et al,^Citation44 (OC) Szulc et al^Citation52
BMD	Indridason et al,^Citation42 Stern et al,^Citation47 Szulc et al^Citation52	Khosla et al,^Citation40 Oh et al,^Citation44 Jorgensen et al^Citation45

Abbreviations: PTH, parathyroid hormone; OC, osteocalcin; BMD, bone mass density.

KudlacekSSchneiderBWoloszczukWPietschmannPWillvonsederRAustrian Study Group on Normative Values of Bone MetabolismSerum levels of osteoprotegerin increase with age in a healthy adult populationBone200332668168612810175

 PubMed Web of Science ®Google Scholar

MazziottiGAmatoGSorvilloFIncreased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolismEur J Endocrinol2006154337337716498049

 PubMed Web of Science ®Google Scholar

PulsatelliLDolzaniPSilvestriTSoluble receptor activator of nuclear factor-kappaB ligand (sRANKL)/osteoprotegerin balance in ageing and age-associated diseasesBiogerontology20045211912715105586

 PubMed Web of Science ®Google Scholar

NabipourILarijaniBVahdatKRelationships among serum receptor of nuclear factor-kappaB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineral density in postmenopausal women: osteoimmunity versus osteoinflammatoryMenopause200916595095519387415

 PubMed Web of Science ®Google Scholar

OhESRheeEJOhKWCirculating osteoprotegerin levels are associated with age, waist-to-hip ratio, serum total cholesterol, and low-density lipoprotein cholesterol levels in healthy Korean womenMetabolism2005541495415562379

 PubMed Web of Science ®Google Scholar

Mezquita-RayaPde la HigueraMGarciaDFThe contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal womenOsteoporos Int200516111368137415711777

 PubMed Web of Science ®Google Scholar

KhoslaSArrighiHMMeltonLJ3rdCorrelates of osteoprotegerin levels in women and menOsteoporos Int200213539439912086350

 PubMed Web of Science ®Google Scholar

Fahrleitner-PammerADobnigHPiswanger-SoelknerCOsteoprotegerin serum levels in women: correlation with age, bone mass, bone turnover and fracture statusWien Klin Wochenschr2003115929129712793029

 PubMed Web of Science ®Google Scholar

IndridasonOSFranzsonLSigurdssonGSerum osteoprotegerin and its relationship with bone mineral density and markers of bone turnoverOsteoporos Int200516441742315776220

 PubMed Web of Science ®Google Scholar

LiuJMZhaoHYNingGRelationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20–75Calcif Tissue Int20057611615455183

 PubMed Web of Science ®Google Scholar

UemuraHYasuiTMiyataniYCirculating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal womenJ Endocrinol Invest200831216316818362509

 PubMed Web of Science ®Google Scholar

RogersASalehGHannonRAGreenfieldDEastellRCirculating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal womenJ Clin Endocrinol Metab200287104470447512364420

 PubMed Web of Science ®Google Scholar

HanKOChoiJTChoiHAThe changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on boneClin Endocrinol (Oxf)200562334935315730418

 PubMed Web of Science ®Google Scholar

ChibaYOnouchiTIkedaTAdachiJTamuraYHoriuchiTImplications of measuring soluble receptor activators of nuclear factor-kappaB ligand and osteoprotegerin in bone metabolism of elderly womenGerontology200955327528019158438

 PubMed Web of Science ®Google Scholar

SternALaughlinGABergstromJBarrett-ConnorEThe sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo studyEur J Endocrinol2007156555556217468191

 PubMed Web of Science ®Google Scholar

JorgensenLVikAEmausNBone loss in relation to serum levels of osteoprotegerin and nuclear factor-kappaB ligand: the Tromso studyOsteoporos Int201021693193819701599

 PubMed Web of Science ®Google Scholar

SzulcPHofbauerLCHeufelderAERothSDelmasPDOsteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone statusJ Clin Endocrinol Metab20018673162316511443182

 PubMed Web of Science ®Google Scholar

Gannage-YaredMHFaresFSemaanMKhalifeSJambartSCirculating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male populationClin Endocrinol (Oxf)200664665265816712667

 PubMed Web of Science ®Google Scholar

OhKWRheeEJLeeWYCirculating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged malesClin Endocrinol (Oxf)2005621929815638876

 PubMed Web of Science ®Google Scholar