Ca&Bone

[RANKL-specific denosumab in the treatment of osteoporosis - Possible adverse effects of long-term use]

TANKÓ László

APRIL 15, 2009

Ca&Bone - 2009;12(01)

[According to the results of a recent clinical trial, the antiresorptive effect of a single 60-mg injection of denosumab, a monoclonal antibody specific to RANKL (receptor activator of NFκB ligand) substantially exceeds the effect of alendronate (70 mg weekly). Despite these differences, 1-year increases in bone density at the lumbar spine are virtually identical for both agents. The author summarizes experimental and clinical observations illustrating potential consequences of osteoclast deficiency and a constantly low rate of bone resorption for osteoblast function, bone mineralization, bone quality parameters, and mechanical properties, which all may have important implications for bone fragility. These observations also raise the question whether treatment efficiency is truly improved by aggressively pushing the limits of antiresorptive action.]

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[Denosumab - pharmacokinetic and clinical evidences]

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[Denosumab is a fully human monoclonal antibody to RANKL modifying bone resorption in a rapid, sustained and reversible way. In postmenopausal women with low bone mineral density, denosumab 60 mg every 6 months increased mineral density, and reduced bone turnover. In postmenopausal women, it reduced the risk of vertebral, hip, and non-vertebral fractures. Increase in body mass index and reduction in bone turnover was more pronounced with denosumab than with alendronate. In patients who were switched from alendronate to denosumab, positive effects on bone were more pronounced than in those continuing alendronate. Denosumab was safe and well tolerated, and it holds the promise of becoming an efficacious therapy for postmenopausal osteoporosis.]

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[Management of hip fractures: practice, results, and problems in the last decade]

KRICSFALUSY Mihály, FLÓRIS István, CSERHÁTI Péter

[Among fractures attributable to osteoporosis, hip fractures are associated with the most severe consequences and the greatest costs. Surgical therapy for this condition is continuing to improve. Increasingly recent implants and techniques are being developed and introduced to successfully control postoperative adverse events. The authors briefly outline actual practice in Hungary and present some results of the follow-up of their patients in the last decade. These show that, in order to improve outcomes of hip fracture patients, all domains of management need to be addressed.]

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[Rehabilitation of patients with osteoporotic bone fractures]

BORS Katalin

[Consequences of osteoporotic bone fractures are increased mortality, decreased quality of life, and increased direct and indirect costs. After the assessment of remaining function and the level of independence, the goal of rehabilitation is to reach the highest level of function and independence possible, thus decreasing morbidity and mortality, improving the overall quality of life, and decreasing costs.]

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[INTRODUCTION - Quantitative Ultrasound (QUS) examination of the bones provides information about not only bone mineral mass but also its quality. Adaptation of the method to the continuous growing of body size allowed its pediatric use. However, for introduction into routine use, a normal reference range in healthy children has to be established. The primary aim of this study was to establish the Hungarian reference range for QUS of the bone - in both genders and across a wide range of ages. As a secondary aim, QUS and the bone density were compared to internationally accepted data to comparatively determine correlations of specific QUS measurements to photon absorption based values. SUBJECTS AND METHODS - Measurement was performed on the calcaneus by Achilles Insight (Lunar, WI) device. Bone Mineral Density (BMD) of the lumbar spine was measured using the Double X-ray Absorptiometry (DXA) device DPX-L (Lunar, WI). Latter was also used to measure total body calcium content. Measurements were performed in 154 healthy boys and girls aged 5 to 18 years. We analyzed data as a function of age, and correlated results of he two types of measurement. RESULTS - Gender-specific reference ranges for normally developing children of the above ages were built up for Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS). BUA showed the best correlation to BMD. SOS and Stiffness Index (SI) derived from BUA and SOS, correlated weaker to BMD, consonantly with the fact that SOS reflects bone elasticity (quality) rather than bone mineral mass. CONCLUSION - These newly constructed normal ranges can provide a basis of performing pediatric bone examinations using QUS, which is less expensive and more mobile.]

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[INTRODUCTION - The bone remodelling process of 81 patients with metastatic prostate cancer was analyzed and correlated to PSA levels. PATIENTS AND METHODS - The patients were recruited from 9 collaborating urology departments. Levels of β-CrossLaps, BALP, urine calcium and urine phosphate were measured. All patients were treated identically (TUR plus an LH-RH analogue or MAB), according to GCP guidelines. After the appearance of metastasis, the patients also received a bisphosphonate compound (clodronate). RESULTS - Bone degradation and formation showed a correlation both in living and deceased patients, indicating that the two processes are not independent. A progressive decrease in the PSA level was associated with a decrease in the β-CrossLaps level. CONCLUSION - In addition to PSA, β-CrossLaps and BALP, two markers of bone metabolism, might prove good predictors of metastasis formation and of response to therapy. Evaluation of the markers relative to agedependent osteoporosis can further improve their predictive value.]

Clinical Neuroscience

[The connection between the socioeconomic status and stroke in Budapest]

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[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]