The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption

Hofbauer, Lorenz C.; Khosla, Sundeep; Dunstan, Colin R.; Lacey, David L.; Boyle, W J; Riggs, B. Lawrence

doi:10.1359/jbmr.2000.15.1.2

Cited by 1,058 publications

(754 citation statements)

References 97 publications

(289 reference statements)

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“…OPG is a soluble secreted decoy receptor of RANKL (20,21). OPG mRNA and protein are found on osteoblastogenic precursors (22). Thus, the effects of RANKL in promoting bone resorption are counterbalanced by the effects of OPG.…”

mentioning

confidence: 99%

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RANKL:Osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

Rouster‐Stevens¹,

Langman²,

Price³

et al. 2007

Arthritis & Rheumatism

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Objective. To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL: osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease.Methods. Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects.Results. At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL: OPG ratio compared with that in healthy children (mean ؎ SD 2.19 ؎ 3.03 and 0.13 ؎ 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of ؊1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than ؊1.5 (P ‫؍‬ 0.038). Lumbar spine BMD Z scores (mean ؎ SD ؊0.13 ؎ 1.19 [range ؊2.10 to 2.85]) were inversely associated with the duration of untreated disease (R ‫؍‬ ؊0.50, P ‫؍‬ 0.003).Conclusion. Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.Children with rheumatic disease have decreased bone mineral density (BMD). Studies of BMD have primarily evaluated patients with juvenile idiopathic arthritis (JIA), and an inverse correlation between higher disease activity and lower BMD has been demonstrated in children with arthritis (1-4). Not surprisingly, patients exposed to corticosteroids were observed to have lower bone density (3,4), although bone density also remained low in the absence of corticosteroid exposure (2,5). Recently, a prospective study evaluating children with JIA compared with healthy control subjects demonstrated that not only did children with JIA have decreased bone mineral content at baseline, but that over time the patients had a less-than-expected age-appropriate gain in bone mass (6).Limited data exist concerning bone metabolism in children with juvenile dermatomyositis (DM), which is the most common pediatric inflammatory myopathy, with an annual incidence in the US of 3.2 cases per 1 Dr.

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confidence: 99%

“…The RANKL:OPG ratio in serum, rather than the individual protein concentrations, has been suggested to be the critical factor in determining osteoclastic activation at the level of bone, with higher serum RANKL:OPG ratios being a marker for upregulation of osteoclastogenesis (22).…”

mentioning

confidence: 99%

RANKL:Osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

Rouster‐Stevens¹,

Langman²,

Price³

et al. 2007

Arthritis & Rheumatism

View full text Add to dashboard Cite

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“…Moreover, the presence of RANKL in organs such as lymph nodes, spleen, thymus, and intestinal lymphoid patches has been described (9,10,18). RANKL is increased upon exposure to factors that promote osteoclast development, such as vitamin D 3 and prostaglandin E 2 (PGE 2 ), which also diminish the expression of OPG by osteoblasts (19). RANKL also plays an important role in differentiation of osteoclasts from their precursor cells and promotes increased activity and survival of these cells by inducing antiapoptotic effects, leading to bone resorption (8,15).…”

mentioning

confidence: 99%

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Neumann

Müller‐Ladner

2005

Arthritis & Rheumatism

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“…Interaction between OPG-L and RANK initiates a signaling and gene expression cascade resulting in the promotion of osteoclast formation from the precursor pool. In this setting, OPG, which is secreted by osteoblasts, but also expressed in many other tissues, acts as a soluble competitive binding partner for RANK-L, which inhibits osteoclast formation and, consequentially, bone resorption [24] (Fig. 2).…”

Section: Osteocytesmentioning

confidence: 99%

“…Using the same effector mechanism, namely OPG/OPG-L interaction, many cytokines and calciotropic hormones therefore seem to exert what are sometimes dual effects on bone formation and/or resorption [24].…”

Section: Systemic Regulation Of Bone Remodelingmentioning

confidence: 99%

Biology of bone and how it orchestrates the form and function of the skeleton

Sommerfeldt

Rubin

2001

European Spine Journal

163

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IntroductionThe skeleton's principal role as a structure has predisposed bone to the unfortunate reputation of being an inert and static material. Given bone tissue's ability to adapt its mass and morphology to functional demands, its ability to repair itself without leaving a scar, and its capacity to rapidly mobilize mineral stores on metabolic demand, it is in fact the ultimate "smart" material [43] and a dynamic example of "form follows function" in biological systems [45]. Considering the ever-growing number of patients who suffer from devastating disorders of the skeleton and the ever-increasing opportunities inherent in the post-genomics era to treat diseases and injuries to bone [44], it is critical for both the physician and the scientist to more fully understand the biology of bone and how its ability to form and resorb tissue ultimately orchestrates the structural and metabolic successes of the skeleton. CellsThree distinctly different cell types can be found within bone: the matrix-producing osteoblast, the tissue-resorbing osteoclast, and the osteocyte, which accounts for 90% of all cells in the adult skeleton. Osteocytes can be viewed as highly specialized and fully differentiated osteoblasts; Abstract The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel -the local resorption and formation of bone -which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

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The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption

Abstract: ABSTRACT

Cited by 1,058 publications

References 97 publications

RANKL:Osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

RANKL:Osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Biology of bone and how it orchestrates the form and function of the skeleton

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