[The pathogenic and clinical significance of the RANK-RANKL-osteoprotegerin system in rheumatoid arthritis]


DECEMBER 23, 2011

LAM KID - 2011;1(03)

[Rheumatoid arthritis (RA) is characterised by increased local and generalised bone resorption, which manifests in the develoment of marginal erosions and generalised osteoporosis, respectively. An increasing number of data suggest that lymphocytes, proinflammatory cytokines and other mediators involved in inflammation contribute to arthritic bone resorption. Therefore, the term ‘osteoimmunology’ has also become widely used. In RA, Receptor Activator of Nuclear Factor kappa B (RANK) and its ligand (RANKL) play a crucial role in bone resorption. These proteins, which belong to the tumor necrosis factor a (TNF-a) receptor and TNF ligand superfamilies, respectively, activate osteoclasts while interacting with T cells, synovial fibroblasts and other cytokines (e.g. IL-1, IL-17), which results in bone resorption. Osteoprotegerin (OPG) is a decoy receptor that also belongs to the TNF receptor family and inhibits RANK-RANKL interactions. There is increased RANKL production and decreased OPG production in RA. The interaction of RANKL with IL-17 is particularly important. Regarding therapy, sulfasalazine, methotrexate and biological agents, especially TNF inhibitors suppress RANKL-mediated bone resorption and thus the development of joint erosions. RANKL-RANK interaction can be directly inhibited by recombinant OPG or anti-RANKL antibody (denosumab). Among these agents, denosumab gave promising results in experiments performed in animal models of arthritis. These were followed by a phase II human RA trial, which proved that denosumab decreased MRI erosion scores in RA.]



Further articles in this publication


[Osteonecrosis of the jaws: real and unreal scares]


[Osteonecrosis caused by bisphosphonates has been known for a long time, but it is still not widely known. Some people overestimate the danger caused by this disease, whereas others underrate it. In this paper, we summerise data from the international literature and our experiences concerning 93 patients treated at our clinic. We discuss the already known details of the pathomechanism of this disease, its risk factors, the diagnostic methods, the specific stages of the disease and the treatment approaches. Considering the difficulties of treatment, we can't emphasise enough the importance of prevention, since the development of this complication can be minimised even in patients at risk with dental sanation before the bisphosphonate therapy and/or with further intervention performed with antibiotic preventive therapy. We must also point out the importance of early diagnosis and of directing these patients to the appropriate specialist units.]


[Extraskeletal effects of parathyroid hormone]

KISS Zoltán, MUCSI István, TÚRI Sándor, SZABÓ András, KISS István, SZEBENI Andrea, KECSKEMÉTI Valéria, TÓTH Miklós, LAKATOS Péter

[The parathyroid gland and its product, parathyroid hormone (PTH) have been subjects of interests in biomedical research for 150 years. Early studies, understandably, concentrated on the primary function: the regulation of serum calcium level. In the past few decades, however, more and more data have shown that, in contrast with the classical view, PTH receptors are expressed not only on bone and kidney cells, but in almost all organs of the human body. Therefore, the effect of PTH obviously cannot be limited to the regulation of bone and mineral metabolism. Systemic symptoms of hyperparathyroidism also became more understandable and explicable by the results of studies on the extraskeletal effects of PTH. Despite the intensive research, the mechanisms of PTH-mediated effects are not well understood in a number of areas. Therefore, it is of great importance to perform further studies in this field, which will hopefully expand our knowledge soon. In our current work, we aim to summarise the nonclassical, extraskeletal effects of PTH (that is, those not related to the regulation of bone metabolism and kidney function) and the results of related studies.]


[The results of the study - Calcium supplementation as a part of basic therapy of osteoporosis is more than a routine step]

LAKATOS Péter, SPEER Gábor, DOMBAI Péter, ZAJZON Gergely

[Calcium intake is considered the base therapy of osteoporosis treatment. It is known that in case of inadequate calcium intake, specific anti-osteoporotic drugs are inefficient. In the present study, we aimed to investigate the alimentary and supplementary calcium intake among Hungarian osteoporotic patients, using a nationwide representative survey. Patients with osteoporosis were enrolled in the study. We determined the total alimentary calcium intake and the average supplementary dose. In some cases, total calcium intake was lower than recommended, in other cases it was significantly higher than that. In some cases, bone density showed a positive correlation with calcium intake. Vitamin D supplementation complied with current recommendations.]


[Personal genome - brave new world?]

ÁRVAI Kristóf, KÓSA János Pál


[Treatment of postmenopausal osteoporotic women with strontium ranelate: results at 10 years]


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BOÉR Katalin, NÉMETH Zsuzsanna

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Hungarian Radiology

[A paradox of articular protective phenomenon: more serious-damaged rudimentary hand in rheumatoid arthitis]

SZÁNTÓ Dezső, SZŰCS Gabriella, DITRÓI Edit

[INTRODUCTION - The joints have been secured from rheumatoid arthritis by diminution of biomechanical effeciency. This effect was analyzed and named articular protective phenomenon three decades ago. CASE REPORT - A case of bilateral rheumatoid arthritis associated with unilateral developmental abnormality hand and bronchial asthma in a 35 year old female patient is presented. Her left 2nd, 3rd, 4th and 5th metacarpal bones moreover her fingers had not evolved. The patient has been treated by antiasthmatic steroid drugs for five years. Rheumatoid disorders of the affected left hand were more severe, than the abnormality of the normal upper limb. Eight years later the most severe bony lesions (ankylosis and mutilation) appeared on this side, only. CONCLUSION - The patient's hand was not saved by inborn bone defect in rheumatoid arthritis. The absence of articular protective phenomenon can be explained by the undisturbed innervation of limb, the motility of hypotrophic carpus besides to steroid-induced suppression.]

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[Hip joint involvement in rheumatoid arthritis: pathological features and orthopaedic treatment]


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Lege Artis Medicinae

[Rituximab therapy in rheumatoid arthritis]

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[Rheumatoid arthritis is a chronic, lifelong disease that causes severe joint deformity, reduces quality of life, and, if not treated appopriately, leads to disability and substantial premature mortality. Its treatment is a multistep procedure, where different grades of treatment options follow each other. Besides traditional, diseasemodifying antirheumatic drugs (DMARDs) and biological therapies inhibiting TNF, a new therapautic option is the use of a chimeric antibody, rituximab, which inhibits B lymphocyte function. This drug is an effective and safe choice for those patients who have received various anti- TNF therapies or do not tolerate TNF inhibition.]


[Inhibition of receptor activator of nuclear kappa-B ligand: pathophysiology and preclinical data]


[Bone remodeling is a lifelong process, in which the balanced functions of osteoclasts and osteoblasts have a key role. In certain conditions, for example during the dramatical hormonal changes in the postmenopausal period, the upset of this balance leads to a pathologically increased bone loss. Such conditions lead to an increased bone loss, which results in an increased risk of fractures. Bone resorption is primarily regulated by a member of the tumor necrosis factor family, receptor activator of nuclear factor κB ligand, which plays a central role in the development, function and survival of osteoclasts. Catabolic effects of this ligand is inhibited by another member of the tumor necrosis factor family, osteoprotegerin, which binds to the ligand and prevents its interaction with its receptor, the receptor activator of nuclear factor κB. Osteoclast activity is at least partly dependent on the relative balance of the ligand and osteoprotegerin. It has been shown in a number of animal models that inhibition of the ligand markedly decreases bone resorption and increases cortical and cancellous bone volume, density and strength, without having any significant effect on other organs. On the basis of these findings, inhibition of receptor activator of nuclear κB ligand is a promising therapy of conditions characterised by increased bone loss. In phase 3 clinical trials, denosumab therapy significantly increased bone mineral density at various regions of the skeleton and significantly decreased the levels of bone turnover markers compared with placebo and alendronate therapy, and significantly decreased the incidence of new vertebral, total hip and nonvertebral fractures compared with placebo. On the basis of these findings, denosumab therapy offers a novel, revolutionary solution for the treatment of postmenopausal osteoporosis.]