• Korean Journal of Clinical Pharmacy
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• v.30 no.3
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• pp.196-205
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• 2020

Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1^st, 2017 to January 31^st, 2020. Risk factors were identified using quantitative N-gram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (T-score), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion: Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis. Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.131-137
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• 2018

Background: In South Korea, 22.3% of women ${\geq}50years$ of age and 37% of women ${\geq}70years$ of age visit the doctor to obtain treatment for osteoporosis. According to the analysis of the National Health Insurance Services claim data between 2008 and 2012, the number and incidence of hip and vertebral fractures increased during the same period. Denosumab, a newly marketed medicine in Korea, is the first RANK inhibitor. Methods: A cost-utility analysis was conducted from a societal perspective to prove the superiority of denosumab to alendronate. A Markov cohort model was used to investigate the cost-effectiveness of denosumab. A 6-month cycle length was used in the model, and all patients were individually followed up through the model, from their age at treatment initiation to their time of death or until 100 years of age. The model consisted of eight health states: well; hip fracture; vertebral fracture; wrist fracture; other osteoporotic fracture; post-hip fracture; post-vertebral fracture; and dead. All patients began in the well-health state. In this model, 5% discounted rate, two-year maximum offset time, and persistence were adopted. Results: The total lifetime costs for alendronate and denosumab were USD 5,587 and USD 6,534, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus alendronate was USD 20,600/QALY. Given the ICER threshold in Korea, the results indicated that denosumab was remarkably superior to alendronate. Conclusion: Denosumab is a cost-effective alternative to the oral anti-osteoporotic treatment, alendronate, in South Korea.

• The Korean journal of internal medicine
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• v.39 no.1
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• pp.148-159
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• 2024

Background/Aims: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. Methods: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. Results: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. Conclusions: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

• The Korean Journal of Pain
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• v.30 no.2
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• pp.86-92
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• 2017

Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption. Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of resorption performed by activated osteoclasts, are still the drugs of choice to prevent and treat osteoporosis. The merits of denosumab are reversibility targeting the RANKL, lack of adverse gastrointestinal events, improved adherence due to convenient biannual subcutaneous administration, and potential use with impaired renal function. The known adverse reactions are musculoskeletal pain, increased infections with adverse dermatologic reactions, osteonecrosis of the jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3 days, with maximum reduction occurring by 1 month. The mean time to maximum denosumab concentration is 10 days with a mean half-life of 25.4 days. In conclusion, the convenient biannual subcutaneous administration of 60 mg of denosumab can be considered as a first-line treatment for osteoporosis in cases of low compliance with BPs due to gastrointestinal trouble and impaired renal function.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.185-190
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• 2022

Background: Denosumab (Prolia®) is administered every 6 months for osteoporosis treatment. Co-administration of calcium and vitamin D is required to minimize hypocalcemia risk. We evaluated clinical outcomes based on the administration interval of denosumab and co-prescription with calcium-vitamin D combination products. Methods: A retrospective study was conducted using electronic medical records from 668 patients who started denosumab therapy between January 1 and December 31, 2018, at Seoul National University Bundang Hospital. Clinical outcomes, as measured by changes in T-score, were evaluated by the intervals and concurrent prescriptions with calcium-vitamin D combination products. Results: Of the 668 patients, 333 patients met the eligibility criteria. These patients were divided into two groups based on appropriateness of the administration interval: "Appropriate" (304 patients, 91.3%) and "Inappropriate" (29 patients, 8.3%). T-score changes were significantly higher in the "Appropriate" than in the "Inappropriate" group (0.30±0.44 vs. 0.13±0.37, p=0.048). At the beginning of the treatment, 221 patients (66.4%) were prescribed calcium-vitamin D combination products, but the changes in T-scores were not significantly different by the prescription status of the product (0.29±0.46 vs. 0.28±0.38, p=0.919). Conclusion: T-scores were significantly improved in patients with appropriate administration intervals. No significant changes in T-scores were observed by the prescription status with calcium-vitamin D combination products. For optimal treatment outcomes, prescribers should encourage adherence to the approved prescription information on dosage and administration, and pharmacists should provide medication counseling for patients.

• Restorative Dentistry and Endodontics
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• v.44 no.4
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• pp.42.1-42.16
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• 2019

Antiresorptive drugs (ARDs), such as bisphosphonates or denosumab, that prevent bone resorption are widely used in patients with osteoporosis or with cancer that has metastasized to the bones. Although osteonecrosis of the jaw (ONJ) is a well-documented complication of ARD use, the benefits ARDs outweigh the complication. Thus, research has focused on finding ways to prevent or reduce the risk of developing ONJ. Dentists, as part of a multi-professional team, have a critical role in preventing ONJ. However, many dentists tend to hesitate to provide dental care to patients with ONJ, or tend to think that it is a problem to be dealt with by oral surgeons. This review gives an overview of ARD-related ONJ and provides the guidelines for dental care in patients taking ARDs to lower the risk of developing ONJ.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1503-1510
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• 2014

Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor ${\kappa}B$ ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.1
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• pp.3-8
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• 2019

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2103-2103
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• 2015

• Journal of Oral Medicine and Pain
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• v.47 no.1
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• pp.1-9
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• 2022

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents and bone-modifying agents. It is of the utmost importance to know the management of the MRONJ to improve the patient's quality of life. This study comprehensively reviews the current definitions of MRONJs, and antiresorptive medications, clinical manifestation and staging, risk factors, treatment strategies, and prevention methods of MRONJ. The disease is defined as an exposure of bone and osteonecrosis of the jaw in the oral cavity for at least 8 weeks in patients taking antiresorptive drugs or antiangiogenic agents and with no history of radiotherapy treatment of the jaws. Many articles have reported risk factors associated with MRONJ such as systemic diseases, antiresorptive medication, oral infection, and poor oral hygiene. Osteonecrosis and antiresorptive medications including bisphosphonate and denosumab have been strongly associated, but the pathology of MRONJ is only limited. Hence, an effective and appropriate management and treatment for MRONJ is still to be defined. The objectives of MRONJ treatment are to minimize osteonecrosis and relieve symptoms, and many treatments are suggested from conservative treatment to marginal resection, but this remains controversial. Appropriate treatment of MRONJ remained difficult, although many studies are being covered.