[Denosumab - pharmacokinetic and clinical evidences]


APRIL 15, 2009

Ca&Bone - 2009;12(01)

[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.]


  1. Semmelweis Egyetem, Általános Orvostudományi Kar, I. Sz. Belgyógyászati Klinika



Further articles in this publication


[Antiresorption - same goal, different ways]


[Antiresorption - same goal, different ways]




[2009;12(01) Moot News]


[Dear Readers and Colleagues!]



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

TANKÓ László

[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.]


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


[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.]

All articles in the issue

Related contents


[Quality of life of patients with osteoporosis in Hungary]

VOKÓ Zoltán, INOTAI András, HORVÁTH CSABA, BORS Katalin, SPEER Gábor, KALÓ Zoltán

[AIM - The aim of our study was to estimate the loss of quality of life due to osteoporotic fractures. We performed a cross-sectional study including 840 patients in 21 centers that specialise in the care of patients with osteoporosis and in acute care of fractures. METHODS - Patients were selected randomly and stratified for the location of and time elapsed since the fracture. Quality of life (QoL) was assessed by the Qualeffo-41 and the EuroQol-5D questionnaires. RESULTS - Patients with morphometric fractures of more than one vertebra had the lowest median EQ-5D index value (0.59). Symptomatic vertebral, hip and arm fractures also considerably decreased QoL. Patients with morphometric fractures of more than one vertebra had the lowest total Qualeffo-41 score. When controlled for age and gender, patients with hip fracture or morphometric vertebral fracture had at least 0.2 less mean utility values than had osteoporotic patients without history of fracture. Patients with more than a oneyear history of hip fracture had QoL scores as low as had patients with an acute fracture. In case of wrist and arm fractures, the acute loss of QoL somewhat decreased with time. CONCLUSION - In conclusion, osteoporotic fractures, especially hip and vertebral fractures result in a significant loss of patients’ quality of life. Our results show that physicians need to pay a close attention to morphometric vertebral fractures, which contribute to a great loss of human capital.]

Clinical Neuroscience

[Management of bone metabolism in epilepsy ]

UÇAN TOKUÇ Ezgi Firdevs , FATMA Genç, ABIDIN Erdal, YASEMIN Biçer Gömceli

[Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice. ]


[Evaluation of quality of life following treatment with calcitonin nasal spray in patients with osteoporosis: preliminary results of the MERLIN study]


[INTRODUCTION - MERLIN (Management of Osteoporosis in Elderly with Calcitonin) is an open-label, multicenter, prospective, follow-up study conducted in Hungary, part of which is to assess the impact of treatment with Miacalcic, - an intranasal salmon calcitonin, on the quality of life (QoL) among patients with osteoporosis. In this paper we report the preliminary results of the MERLIN study. PATIENTS - The study initially involved 1949 senior patients (aged >65 years) to whom calcitonin was prescribed for osteoporosis according to the application instructions. Patients presented at outpatient clinics and consisted of two groups; they were either newly diagnosed or they had been receiving a therapy for osteoporosis other than calcitonin. METHODS - This latter group discontinued their previous treatment and all patients received 200 IU intranasal salmon calcitonin (SCT) once daily for three months. Patient and physician questionnaires were used to collect information on the patients' QoL (EQ-5D VAS) and their general well-being at baseline and at follow-up visits at week 4 and week 12. RESULTS - Calcitonin use was associated with improvements in all EQ-5D domains and component scores as well as in VAS. Patients with previously known osteoporosis who, switched to calcitonin therapy achieved better results (0,046 QALY), than the newly diagnosed patients (0,0405 QALY). CONCLUSIONS - We conclude that intranasal SCT 200 IU daily is safe and effective in improving QoL of both, male and female patients with low bone mineral density.The conclusions that can be drawn from this study are limited due to the lack of a control group and to the unblinded design. Further placebo-controlled studies are needed to confirm these results. Nevertheless, our study was the first in Hungary to evaluate the quality of life impact of an osteoporosis treatment, and hopefully it will be followed by more such studies directed to other osteoporosis treatments.]


[Bone metabolism and body mass index in postmenopausal women]

TÁRCZY Csaba, TOLDY Erzsébet, SZERB János, VARGA László

[INTRODUCTION - In addition to several other causes constitutional factors play an important role in the development of osteoporosis.Various aspects of bone metabolism were examined to explain the differences in bone density between women with low and high body mass index (BMI). PATIENTS AND METHOD - One hundred and ninetytwo postmenopausal women were included in the study. Bone density was measured by forearm densitometry.To assess bone formation, serum osteocalcin levels were measured, while the rate of bone absorption was estimated from C-terminal telopeptide levels of collagen type I measured in urine and blood. RESULTS - The prevalence of osteoporosis was higher in women with low BMI than in those with normal or higher BMI. Bone metabolism - both formation and absorption - was increased in both groups, however, in women with low BMI this increase was more pronounced and bone metabolism tended to be shifted to absorption compared to patients with normal or higher BMI. CONCLUSION - Postmenopausal lean women have accelerated bone metabolism compared to obese women. This fact and the shift to absorption may be the main reasons for the higher frequency of osteoporosis found by densitometry in women with low BMI than in those with higher BMI.]


[Bone mineral density and diabetes mellitus - First results]


[INTRODUCTION - Data on bone mineral density (BMD) in diabetes mellitus are contradictory in the literature. Early studies described a decreased bone mineral density in type 1 diabetes mellitus (T1DM), but recent studies report no osteopenia in T1DM.The BMD may depend on the quality of treatment for diabetes mellitus and on the presence of chronic complications. In type 2 diabetes mellitus (T2DM) the BMD is not decreased, occasionally it can even be increased. PATIENTS AND METHODS - Bone mineral density was measured in 122 regularly controlled diabetic patients (T1DM: n=73, mean age: 43.6±11.1 years,T2DM: n=49, mean age: 61.8±9.8 years) by dual energy X-ray absorptiometry at the lumbar spine and at the femur. Results were compared to those of 40 metabolically healthy control persons with a mean age of 47.5±11.9 years.The patients’ carbohydrate metabolism was assessed by the average HbA1c level of the last three years.These values were 7.9±1.4 % in T1DM, and 7.5±1.7 % in T2DM. BMDs were classified based on the T-score and Z-score using the WHO criteria. RESULTS - There was no significant difference in T1DM or in T2DM compared to the reference group in the prevalence of either osteoporosis or of osteoporosis and osteopenia combined. CONCLUSION - BMD was not found to be decreased in patients with well-controlled metabolism compared to healthy controls.]