[Extraskeletal effects of parathyroid hormone]

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

DECEMBER 23, 2011

LAM KID - 2011;1(03)

[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.]



Further articles in this publication


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


[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.]


[Personal genome - brave new world?]

ÁRVAI Kristóf, KÓSA János Pál


[The relationship of coronary heart disease and bone from a different point of view: is lumbar vertebral density a positive predictor of coronary heart disease in women?]


[BACKGROUND - A number of international data demonstrate the relationship between cardiovascular disease and bone density, osteoporosis and osteopenia. It is possible that bone formation/remodeling and vascular calcification are influenced by common pathogenetic factors (adipocytokines, inflammatory processes). Our aim was to assess this relationship among Hungarian patients. PATIENTS AND METHODS - We examined 82 patients (49 men and 33 women). The patients underwent a DEXA measurement and fasting blood sampling with full metabolic profiling within one month following an elective coronarography. Coronary state was characterised by the Gensini-score. RESULTS - Femur neck T-score values showed significant decreases in the CHD+ group (patients having at least one significant coronary stenosis), compared with the CHD- group (patients with no history of significant coronary stenosis) (-0.22 vs. -0.85, p<0.05) when the two genders were examined together. In women, lumbar BMD showed a significant positive correlation (r=+0.37, p=0.03), and the levels of adiponectin and HDL-cholesterol showed significant negative correlations (r=-0.311, p=0.04, és r=-0.38, p=0.03) with the Gensini-score. Neither the HOMA-index that characterises insulin resistance, nor the majority of conventional lipid and lipoprotein risk factors showed any association with the severity of coronary heart disease. CONCLUSION - On the basis of our results, the relationships between femur and lumbar regions and coronary heart disease are opposite in nature, which is probably explained by the different regulatory mechanisms in these two regions. Adiponectin may have an important role in the regulation of this relationship, which is independent of insulin resistance.]


[The story of DEXA machines]



[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.]

All articles in the issue

Related contents


[Evaluation of bone mineralization in cow’s milk sensitive children]

HIDVÉGI Edit és munkatársai

[BACKGROUND - Patients with cow's milk allergy (CMA) form a potential risk group for osteopenia, because their milk-free diet usually has a low calcium content.The study analyses various parameters of bone mineralization in CMA children. PATIENTS AND METHODS - Twenty-seven CMA patients (mean age: 4.3 years, range: 3-8 years) were enrolled in the study.Transient sensitivity to cow's milk was observed in 20 of 27 patients. During the milk-free diet period (mean duration 11.8 months) children were fed by extensively hydrolysed or soy-based formulas. Seven patients still required a cow's milk free diet at the time of the study. Serum levels of Na, K, Cl, Ca, P and Mg ions, as well as of alkaline phosphatase (AP), parathyroid hormone (PTH), osteocalcin and beta-crosslaps were determined for all 27 patients.The values were compared to those of 20 healthy age-matched controls. Bone mineral densities (BMDs) of CMA patients were also measured. RESULTS - The AP and PTH levels were higher in CMA patients than in the control group (AP: 610.2 U/l vs 499.7 U/l, p<0.01; PTH: 1.56 pmol/l vs 0.83 pmol/l, p<0.03), but all values fell in the normal range.The osteocalcin level was similar in the two groups, and the beta-crosslaps was lower in CMA patients than in the controls (0.92 vs 1.47 ng/ml, p<0.001).There was a positive correlation between both AP and osteocalcin and AP and beta-crosslaps levels.The mean Z score of bone mineral density in patients with CMA was -0.6. In 10 cases the Z score was below -1, which was associated with a significantly elevated PTH level compared to the group of patients with a Z score above - 1 (2.24 pmol/l vs 1.16 pmol/l, p<0.03). CONCLUSION - In children with CMA on a cow's milk free diet, slight disturbances of bone mineralization were observed, therefore, osteodensitometric check-up of these children is recommended.]


[The role of alfacalcidol in the prevention of osteopenia following renal transplantation]


[AIM - The aim of this prospective study was the long-term evaluation of the effect of calcium and alfacalcidol treatment on calcium metabolism in patients with renal transplantation. METHODS - Patients were divided in two groups. Patients in Group 1 (n=159) received calcium substitution, while patients in Group 2 (n=81) were treated with alfacalcidol. Serum Ca, P, Mg, alkaline phosphatase (AP) and PTH levels were determined before and after transplantation regularly for three years. Femur neck and lumbar vertebral bone mineral densities (BMD) were measured at the same time after transplantation. RESULTS - After transplantation the mean serum calcium level significantly increased, while the mean serum phosphate level significantly decreased in both groups. After the operation the PTH levels decreased in both groups and it was found to be more pronounced in the alfacalcidol group.The majority of patients had osteopenia in the follow-up period. Between the third month and the third year after transplantation, BMD increased by 9.4% in Group1, and decreased by 4% in Group 2 at the lumbar spine. At 3 years the mean BMD value at the femoral neck was increased by 6.5% in Group 1, and by 6.7% in Group 2, compared to the 3-month values.The change in BMD was only significant at the lumbar spine, in Group 1 (p=0.019). During the follow-up period osteonecrosis was diagnosed in 6 patients in Group 1 and in 9 cases in Group 2. CONCLUSION - Alfacalcidol treatment decreased secondary hyperparathyroidism more rapidly and effectively, which was also indicated by the more pronounced decrease of serum PTH levels. During the 3 years follow-up period, BMD increased in both groups except for the lumbar spine in Group 2, however, the majority of the patients still had osteopenia.The study could not demonstrate a superiority of alfacalcidol over calcium supplementation in the prevention of posttransplantational osteopenia.]

Clinical Neuroscience

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report


Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.