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Sakuma H, Kanemaru H, Kurokawa A, Soga M, Yamashita M, Nozawa-Kobayashi M, Niimi K, Kobayashi T. Prevalence of MRONJ in patients treated with antiresorptive agents for glucocorticoid-induced osteoporosis. Oral Maxillofac Surg 2025; 29:84. [PMID: 40237920 DOI: 10.1007/s10006-025-01383-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 04/07/2025] [Indexed: 04/18/2025]
Abstract
PURPOSE In this study, we aimed to investigate the incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients with glucocorticoid-induced osteoporosis (GIOP) and to examine risk factors for MRONJ development, as well as the preventive effect of tooth extraction before antiresorptive agent (ARA) administration. METHODS This retrospective study included patients who received ARA to prevent fragility fractures due to GIOP. The cumulative incidence of MRONJ in patients with GIOP was calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to analyze risk factors for MRONJ occurrence. RESULTS The study included 327 individuals. Six patients developed MRONJ; the crude incidence of MRONJ was 1.8%, and the cumulative incidence at 1, 2, 3, 4, and 5 years was 0.32%, 0.97%, 1.35%, 1.85%, and 2.56%, respectively. In this study, 159 teeth were extracted during dental intervention before ARA administration in 58 patients; however, no MRONJ development was observed at the extraction site. Tooth extraction, diabetes mellitus, and duration of ARA administration were not identified as risk factors in this study. CONCLUSIONS The incidence of MRONJ in patients with GIOP was higher than the previously reported incidence in patients with age-related osteoporosis but lower than the incidence in patients using high-dose ARA. The results support the effectiveness of prophylactic procedures to remove the infected lesions as much as possible from the jawbone and periodontal tissue before ARA administration. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Hidenobu Sakuma
- Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274, Gakkocho, Niigata City, 951-8514, Japan.
| | - Hiroko Kanemaru
- Oral Management Clinic for Medical Cooperation, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Akira Kurokawa
- Oral Management Clinic for Medical Cooperation, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Marie Soga
- Oral Management Clinic for Medical Cooperation, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Moe Yamashita
- Oral Management Clinic for Medical Cooperation, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Mai Nozawa-Kobayashi
- Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274, Gakkocho, Niigata City, 951-8514, Japan
- Minamiuonuma City Yukiguni Yamato Hospital Dentistry/Pediatric Dentistry, Minamiuonuma, Japan
| | - Kanae Niimi
- Patient Support Center, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Tadaharu Kobayashi
- Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274, Gakkocho, Niigata City, 951-8514, Japan
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Diab DL, Watts NB. The use of denosumab in osteoporosis - an update on efficacy and drug safety. Expert Opin Drug Saf 2024; 23:1069-1077. [PMID: 39262109 DOI: 10.1080/14740338.2024.2386365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 07/03/2024] [Indexed: 09/13/2024]
Abstract
INTRODUCTION Denosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis. AREAS COVERED Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab. EXPERT OPINION Although bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.
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Affiliation(s)
- Dima L Diab
- College of Medicine, Cincinnati VA Medical Center, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, OH, USA
| | - Nelson B Watts
- Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA
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Jiang Y, Huo Y, Li Y, Kong X, Wang B, Liu F, Zheng X, Li Y, Yang Y, Xu Y, Xue Q, Hu Z, Xiao Y, Ma W, Guo Y, Yu W, Xia W. Randomized, double-blind, placebo-controlled, multicenter study to evaluate efficacy and safety of the denosumab biosimilar MW031 in Chinese postmenopausal women with osteoporosis. Expert Opin Biol Ther 2024; 24:665-672. [PMID: 38752402 DOI: 10.1080/14712598.2024.2352587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis. PATIENTS AND METHODS In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included. RESULTS Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups. CONCLUSION This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis. TRIAL REGISTRATION NCT05215977 (ClinicalTrials.gov.).
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Affiliation(s)
- Yan Jiang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Yanan Huo
- Department of Endocrinology, The Jiangxi Provincial People's Hospital, Nanchang, PR China
| | - Yufeng Li
- Department of Endocrinology, Beijing Pinggu Hospital, Beijing, PR China
| | - Xijian Kong
- Department of Osteoporosis, Henan Provincial Orthopedic Hospital, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Luoyang, PR China
| | - Bingwu Wang
- Department of Spine Surgery, Weifang People's Hospital, Weifang, PR China
| | - Feng Liu
- Department of Geriatrics, Guangzhou First People's Hospital, Guangzhou, PR China
| | - Xin Zheng
- Department of Endocrinology, China Rehabilitation Research Center, Beijing Boai Hospital, Beijing, PR China
| | - Yukun Li
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Yunfa Yang
- Department of Orthopedics, Guangzhou First People's Hospital, Guangzhou, PR China
| | - Yongsheng Xu
- Department of Bone and Joint, Inner Mongolia Autonomous Region People's Hospital, Hohhot, PR China
| | - Qingyun Xue
- Department of Orthopedics, Beijing Hospital, Beijing, PR China
| | - Zhitian Hu
- Department of Clinical Development, Mabwell (Shanghai) Bioscience Co. Ltd, Shanghai, PR China
| | - Yanfeng Xiao
- Department of Clinical Development, Mabwell (Shanghai) Bioscience Co. Ltd, Shanghai, PR China
| | - Wen Ma
- Department of Clinical Development, Mabwell (Shanghai) Bioscience Co. Ltd, Shanghai, PR China
| | - Yinhan Guo
- Department of Clinical Development, Mabwell (Shanghai) Bioscience Co. Ltd, Shanghai, PR China
| | - Wei Yu
- Department of radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Weibo Xia
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China
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Iijima Y, Yamada M, Amano M, Watanabe S, Fujimaru M, Uematsu A, Hino S, Sano M, Horie N, Sakagami H, Kaneko T. Dental Hygienists' Awareness of Medication-Related Osteonecrosis of the Jaw in Private Dental Clinics in Japan. Gerontol Geriatr Med 2024; 10:23337214241292794. [PMID: 39494315 PMCID: PMC11528679 DOI: 10.1177/23337214241292794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/05/2024] [Accepted: 10/03/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose: Medication-related osteonecrosis of the jaw (MRONJ) caused by bisphosphonates (BPs) and denosumab (Dmab) is still a major oral adverse event caused by cancer treatment and may be under-recognized by private dental services. With the aim of reducing the prevalence of MRONJ, this study, which is a pilot study for a planned future large-scale survey, compared knowledge about MRONJ between dental hygienists (DHs) in private dental clinics and those in cancer center hospitals. Methods: We conducted a questionnaire-based survey regarding MRONJ between 1 November 2023 and 31 January 2024 on DHs at a cancer base hospital and a private clinic in Saitama, Japan. We statistically analyzed the data collected using the χ2 test or Fisher's exact test with the level of significance set at 5%. Results: This study included 10 in-hospital and 53 private clinic DHs. The in-hospital DHs had appropriate knowledge of MRONJ. However, compared with the in-hospital DHs, although the private clinic DHs knew that BPs are used for osteoporosis, significantly fewer had knowledge of Dmab (p < .001) or knew that BPs and Dmab could also be used to treat cancer (both p < .001). In addition, few private clinic DHs were aware of MRONJ cases refractory to antibiotic treatment alone (p = .012). Conclusion: These findings suggest that private clinic DHs have less knowledge of MRONJ than those in cancer base hospitals.
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Affiliation(s)
- Yosuke Iijima
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Miki Yamada
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Mai Amano
- Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan
| | - Saya Watanabe
- Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan
| | - Miki Fujimaru
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Ayako Uematsu
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Shunsuke Hino
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Motohiko Sano
- Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan
| | - Norio Horie
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Hiroshi Sakagami
- Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan
| | - Takahiro Kaneko
- Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
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Bhardwaj A, Swe KMM, Sinha NK. Treatment for osteoporosis in people with beta-thalassaemia. Cochrane Database Syst Rev 2023; 5:CD010429. [PMID: 37159055 PMCID: PMC10167785 DOI: 10.1002/14651858.cd010429.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
BACKGROUND Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review. OBJECTIVES To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022. SELECTION CRITERIA Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years. DATA COLLECTION AND ANALYSIS Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life. AUTHORS' CONCLUSIONS Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
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Affiliation(s)
- Amit Bhardwaj
- Department of Orthopaedics, Sengkang General Hospital, Singapore, Singapore
| | - Kye Mon Min Swe
- Department of Population Medicine, University Tunku Abdul Raman, Kajang, Malaysia
| | - Nirmal K Sinha
- Department of Orthopaedics, Manipal University College Malaysia (MUCM), Melaka, Malaysia
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Mochizuki T, Yano K, Ikari K, Hiroshima R, Okazaki K. Comparison of Romosozumab Versus Denosumab Treatment on Bone Mineral Density After One Year in Rheumatoid Arthritis Patients with Severe Osteoporosis: A Randomized Clinical Pilot Study. Mod Rheumatol 2022; 33:490-495. [PMID: 35689558 DOI: 10.1093/mr/roac059] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 04/26/2022] [Accepted: 06/06/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To investigate the effect of romosozumab versus denosumab treatment on bone mineral density (BMD), disease activity, and joint damage in patients with rheumatoid arthritis (RA) and severe osteoporosis. METHODS Fifty-one postmenopausal women were enrolled and randomized equally into two groups to receive either romosozumab or the denosumab. Changes (Δ) in the BMD (at lumbar spine, total hip, and femoral neck), disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and van der Heijde-modified Total Sharp Score (TSS) from baseline to 12 months after treatment were evaluated. RESULTS The ΔBMD at 12 months in the romosozumab and denosumab groups were 10.2 ± 5.6% and 5.0 ± 3.1% (p = 0.002) for the lumbar spine, 3.7 ± 4.9% and 3.5 ± 3.0% (p = 0.902) for total hip, and 3.6 ± 4.7% and 3.2 ± 4.9% (p = 0.817) for femoral neck, respectively. The ΔDAS28-ESR at 12 months in the romosozumab and denosumab groups was 0.14 and 0.22 (p = 0.643), respectively, whereas, the ΔTSS at 12 months was 0.33 and 0.29 (p = 0.927), respectively. CONCLUSIONS Our results suggest that romosozumab treatment was more effective in increasing the BMD at the lumbar spine than denosumab, and may be selected for patients who require a significant increase in the lumbar spine BMD. Moreover, romosozumab may be not affect disease activity and joint damage in patients with RA.
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Affiliation(s)
- Takeshi Mochizuki
- Department of Orthopaedic Surgery, Kamagaya General Hospital, Chiba, Japan
| | - Koichiro Yano
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsunori Ikari
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan.,Division of Multidisciplinary Management of Rheumatic Diseases, Tokyo Women's Medical University, Tokyo, Japan
| | - Ryo Hiroshima
- Department of Orthopaedic Surgery, Kamagaya General Hospital, Chiba, Japan
| | - Ken Okazaki
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
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Kim JW, Kwak MK, Han JJ, Lee ST, Kim HY, Kim SH, Jung J, Lee JK, Lee YK, Kwon YD, Kim DY. Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons. J Bone Metab 2021; 28:279-296. [PMID: 34905675 PMCID: PMC8671025 DOI: 10.11005/jbm.2021.28.4.279] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/15/2021] [Indexed: 12/27/2022] Open
Abstract
Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.
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Affiliation(s)
- Jin-Woo Kim
- Department of Oral and Maxillofacial Surgery, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Mi Kyung Kwak
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Jeong Joon Han
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, Korea
| | - Sung-Tak Lee
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea
| | - Ha Young Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Se Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Junho Jung
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Jeong Keun Lee
- Department of Oral and Maxillofacial Surgery, Institute of Oral Health Science, Ajou University Dental Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Young-Kyun Lee
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yong-Dae Kwon
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Deog-Yoon Kim
- Department of Nuclear Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea
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Hirota M, Takahashi T, Saito Y, Kawabata R, Nakatsuka R, Imamura H, Motoori M, Makari Y, Takeno A, Kishi K, Adachi S, Miyagaki H, Kurokawa Y, Yamasaki M, Eguchi H, Doki Y. Utility of monthly minodronate for osteoporosis after gastrectomy: Prospective multicenter randomized controlled trials. Ann Gastroenterol Surg 2021; 5:754-766. [PMID: 34755007 PMCID: PMC8560613 DOI: 10.1002/ags3.12474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/04/2021] [Accepted: 05/10/2021] [Indexed: 01/22/2023] Open
Abstract
AIM Osteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy. METHODS Of the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L-BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates. RESULTS There was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L-BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (-25.6% vs -1.6%, P < .01) and serum bone-specific alkaline phosphatase (-34.3% vs -20.1%, P < .01). AEs were observed in 26.8% and 9.3% of the patients and treatment completion rates were 77.5% and 89.3% in the MIN and VD groups, respectively. Serious AEs were not observed in either group. CONCLUSION This study demonstrated the safety and efficacy of monthly minodronate, suggesting that this treatment may be useful for osteoporosis after gastrectomy (UMIN000015517).
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Affiliation(s)
- Masashi Hirota
- Department of SurgeryToyonaka municipal hospitalOsakaJapan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
| | - Yurina Saito
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
| | | | - Rie Nakatsuka
- Department of SurgeryOsaka General medical centerOsakaJapan
| | | | | | - Yoichi Makari
- Department of SurgerySakai city medical centerSakaiJapan
| | - Atsushi Takeno
- Department of SurgeryKansai Rosai HospitalAmagasakiJapan
| | - Kentaro Kishi
- Department of SurgeryOsaka police hospitalOsakaJapan
| | | | | | - Yukinori Kurokawa
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
| | - Makoto Yamasaki
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
| | - Hidetoshi Eguchi
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
| | - Yuichiro Doki
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
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Gouli S, Wang J, Patel A, Allerton J. Hypocalcemia in a Patient With Metastatic Prostate Cancer From Denosumab Treatment. Cureus 2021; 13:e17046. [PMID: 34522524 PMCID: PMC8427738 DOI: 10.7759/cureus.17046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2021] [Indexed: 12/24/2022] Open
Abstract
Denosumab is a humanized monoclonal antibody that binds RANKL to inhibit osteoclast activity. It is indicated for the prevention of skeletal-related events (SRE) in patients with solid tumors who have bone metastasis and in patients with multiple myeloma. Hypocalcemia is one of the known side effects of denosumab, which can be prevented with calcium supplementation. We present a case of a 72-year-old male with diagnosed metastatic prostate cancer who had received one dose of denosumab 10 days prior to presentation with fatigue, insomnia, and somnolence. His labs showed severe (Grade 4) hypocalcemia, which improved with intravenous calcium supplementation. This case highlights a known but life-threatening side effect of denosumab and the potential need for prolonged calcium monitoring in patients placed on the drug.
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Affiliation(s)
- Sugam Gouli
- Internal Medicine, Bassett Medical Center, Cooperstown, USA
| | - Jimmy Wang
- Internal Medicine, Bassett Medical Center, Cooperstown, USA
| | - Anush Patel
- Hematology / Oncology, Bassett Medical Center, Cooperstown, USA
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10
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Abstract
Osteoporosis is less common in men than women; however, the mortality rate associated with major fragility fractures is higher in men. The diagnosis of osteoporosis is established by measurement of bone mineral density or by the presence of a fragility fracture, especially spine or hip fracture. However, many men at high risk of fracture will not meet the T-score criteria for osteoporosis, so fracture risk calculation, with a tool such as FRAX, should be performed. Bone-active agents should be prescribed for men at high risk of fracture to decrease fracture risk, and therapy must be individualized.
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Affiliation(s)
- Dima L Diab
- Division of Endocrinology/Metabolism, Department of Internal Medicine, Cincinnati VA Medical Center, University of Cincinnati Bone Health and Osteoporosis, 231 Albert Sabin Way, MSB 7th Floor, Cincinnati, OH 45267, USA.
| | - Nelson B Watts
- Mercy Health Osteoporosis and Bone Health Services, 4760 E. Galbraith Road, Suite 212, Cincinnati, OH 45236, USA
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11
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Tanaka S, Mizutani H, Tsuruya E, Fukuda R, Kuge K, Okubo N. Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study. J Bone Miner Metab 2021; 39:463-473. [PMID: 33387064 DOI: 10.1007/s00774-020-01180-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 11/04/2020] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Denosumab is a humanized IgG2 monoclonal antibody that was approved for the treatment of osteoporosis in Japan in 2013. This study aimed to investigate the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. MATERIALS AND METHODS This 3-year, prospective, observational, post-marketing study included patients who initiated treatment with denosumab (60 mg/6 months) for osteoporosis. Data were assessed at baseline, 3, 6, 12, 24 and 36 months. Key endpoints were adverse events (AEs), adverse drug reactions (ADRs), occurrence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers. Multivariate analyses were conducted to identify predictors of hypocalcaemia and percent change in BMD. RESULTS Overall, 3534 patients were assessed (mean 75.7 years; 89.8% women). In total, 298 patients (8.4%) developed ADRs; the most common was hypocalcaemia (3.9%). Hypocalcaemia risk was significantly increased in patients with creatinine clearance < 30 mL/min, no prior use of bisphosphonates, prior use of calcium and vitamin D preparations, baseline serum calcium < 8.5 mg/dL, and no concomitant use of calcium or vitamin D preparations. Six patients had adjudicated osteonecrosis of the jaw. Lumbar spine BMD increased significantly from baseline (mean percent change: 11.4% at 36 months). All bone turnover markers decreased significantly from baseline. Over 3 years, 3.3% of patients developed a new osteoporotic fracture. CONCLUSIONS This study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. No new safety signals were identified.
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Affiliation(s)
- Sakae Tanaka
- Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hideki Mizutani
- Post Marketing Study Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan.
| | - Eri Tsuruya
- Post Marketing Study Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan
| | - Ryoko Fukuda
- Post Marketing Study Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan
| | - Kiyoka Kuge
- Post Marketing Study Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan
| | - Naoki Okubo
- Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan
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12
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Bouvard B, Briot K, Legrand E, Blain H, Breuil V, Chapurlat R, Duquenne M, Guggenbuhl P, Lespessailles E, Thomas T, Cortet B. Recommandations françaises de la prise en charge et du traitement de l’ostéoporose masculine. ACTA ACUST UNITED AC 2021. [DOI: 10.1016/j.rhum.2021.02.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Matsumoto T, Endo I. RANKL as a target for the treatment of osteoporosis. J Bone Miner Metab 2021; 39:91-105. [PMID: 33057808 DOI: 10.1007/s00774-020-01153-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 08/23/2020] [Indexed: 12/11/2022]
Abstract
Osteoporosis is characterized by compromised bone strength, predisposing to an increased risk of fracture. Because bone is constantly remodeled, and bone mass and structure are determined by the balance between bone resorption and bone formation, it is important to maintain normal bone turnover. Therefore, therapies that reduce bone resorption have been the mainstream of osteoporosis treatment. Receptor activator of nuclear factor-kappa B ligand (RANKL)-RANK signaling was found to play a pivotal role in the regulation of osteoclastic bone resorption, and inhibition of RANKL-RANK system has become an important therapeutic target for the treatment of osteoporosis. Denosumab, a fully human monoclonal anti-RANKL neutralizing antibody, is developed as a drug for the treatment of osteoporosis. This review summarized pharmacokinetic and pharmacodynamic properties of denosumab, clinical studies including phase 2 dose-ranging and its extension study, phase 3 fracture prevention study (FREEDOM) with extension up to 10 years, studies on male osteoporosis (ADAMO study), and on glucocorticoid-induced osteoporosis, along with relevant clinical studies in Japan. In addition, mechanism of denosumab action that can explain its long-term sustained effects, combination and sequential treatment as well as the problems in discontinuation of denosumab, and finally safety of denosumab therapy is discussed.
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Affiliation(s)
- Toshio Matsumoto
- Fujii Memorial Institute of Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima, 770-8503, Japan.
| | - Itsuro Endo
- Department of Bioregulatory Sciences, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan
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14
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Seeto AH, Abrahamsen B, Ebeling PR, Rodríguez AJ. Cardiovascular Safety of Denosumab Across Multiple Indications: A Systematic Review and Meta-Analysis of Randomized Trials. J Bone Miner Res 2021; 36:24-40. [PMID: 32780899 DOI: 10.1002/jbmr.4157] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/20/2020] [Accepted: 08/02/2020] [Indexed: 01/01/2023]
Abstract
The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta-analysis sought to quantify the number of randomized controlled trials (RCTs) of denosumab (against comparators) reporting cardiovascular adverse events (CAEs) and examine the balance of CAEs between treatment arms. MEDLINE, Embase, and clinicaltrials.gov were searched from inception to October 26, 2019, for RCTs of denosumab versus comparators for any indication. Included trials were randomized, enrolled ≥100 participants, and reported bone-related outcomes. Primary outcome for analysis was all CAEs, a composite endpoint representing summation of all CAEs as reported by included trials. Secondary outcomes included major adverse cardiovascular events (MACE). Data were pooled using a fixed effects model to determine relative risk (RR) and 95% confidence interval (95% CI). Risk of bias was assessed using the Cochrane risk-of-bias tool. Of 554 records screened, 49 were included, while 36 reported CAEs. Twenty-seven included trials (12 eligible for meta-analysis) were conducted in 13,202 postmenopausal women. Compared with bisphosphonates, there was a 46% (95% CI 1.05 to 2.02) increase in CAEs (85/2136 events in denosumab-treated versus 58/2131 events in bisphosphonate-treated; seven trials). There was a similar imbalance in a five-point (stroke, myocardial infarction, cardiovascular death, heart failure, atrial fibrillation) MACE endpoint (28/2053 versus 12/2050; RR = 2.33 [1.19 to 4.56]). Compared with placebo-treated women, there was no imbalance in total CAEs (439/4725 events in denosumab versus 399/4467 in placebo; RR = 0.79 [0.41 to 1.52]; seven trials). No imbalance in total AEs (versus bisphosphonates: 0.98 [0.92 to 1.04]; versus placebo: 0.99 [0.98 to 1.01]) occurred. Other indications showed no statistically significant results. The excess CAEs in postmenopausal women treated with denosumab compared with bisphosphonates, but not placebo, indirectly supports claims that bisphosphonates may suppress CAEs. Future trials should use standardized CAE reporting to better describe cardiovascular effects of bone active medications. (PROSPERO: CRD42019135414.) © 2020 American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
| | - Bo Abrahamsen
- OPEN-Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Musculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.,Department of Medicine, HolbaekHospital, Holbaek, Denmark
| | - Peter R Ebeling
- Bone and Muscle Health Research Group, Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, Australia.,Australian Institute for Musculoskeletal Science, St Albans, Australia
| | - Alexander J Rodríguez
- OPEN-Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Bone and Muscle Health Research Group, Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, Australia.,Disorders of Mineralisation Research Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
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15
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Okubo N, Matsui S, Matsumoto T, Sugimoto T, Hosoi T, Osakabe T, Watanabe K, Takami H, Shiraki M, Nakamura T. Relationship Between Bone Mineral Density and Risk of Vertebral Fractures with Denosumab Treatment in Japanese Postmenopausal Women and Men with Osteoporosis. Calcif Tissue Int 2020; 107:559-566. [PMID: 32839843 DOI: 10.1007/s00223-020-00750-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 08/11/2020] [Indexed: 01/22/2023]
Abstract
In this post hoc analysis of the Denosumab Fracture Intervention Randomized Placebo-Controlled Trial (DIRECT) in Japanese postmenopausal women and men with osteoporosis, we evaluated the relationship between vertebral fracture risk and both bone mineral density (BMD) T-score and percent change after 24 months of denosumab treatment at total hip, femoral neck, and lumbar spine. Logistic regression analysis was performed and the proportion of treatment effect explained by BMD in vertebral fracture risk was estimated. The results demonstrate that both total hip BMD T-score and change can be strong predictors of subsequent fracture risk, and that total hip BMD change explained 73%, while T-score explained 23%, of the treatment effect. In contrast, neither femoral neck BMD change nor T-score can predict the effect of denosumab on vertebral fracture risk. Furthermore, although lumbar spine BMD T-score was associated with vertebral fracture incidence, lumbar spine BMD change was inversely related to vertebral fracture risk. Because there was no relationship between lumbar spine BMD change and T-score at 24 months of denosumab treatment, and because there can be small undetectable vertebral deformities that may increase BMD values, these results suggest that lumbar spine BMD change is not a good surrogate for vertebral fracture risk assessment. It is suggested that both total hip BMD change and T-score can be good surrogates for predicting vertebral fracture risk in Japanese patients with osteoporosis under denosumab treatment.ClinicalTrials.gov identifier: NCT00680953.
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Affiliation(s)
| | | | - Toshio Matsumoto
- Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | | | | | | | | | | | - Masataka Shiraki
- Research Institute and Practice for Involutional Diseases, Nagano, Japan
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16
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Mochizuki T, Yano K, Ikari K, Hiroshima R, Nasu Y, Okazaki K. Three-year results of denosumab treatment for osteoporosis in women with rheumatoid arthritis and primary osteoporosis: A clinical observational study. Mod Rheumatol 2020; 31:600-606. [PMID: 32815449 DOI: 10.1080/14397595.2020.1812793] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This study investigated the results of 3 years of denosumab treatment for osteoporosis in women with rheumatoid arthritis (RA) and primary osteoporosis (PO). MATERIALS AND METHODS This study enrolled 112 women with RA (RA group) and 104 women with a PO group who received 60 mg denosumab for 3 years. Bone mineral densitiy (BMD) of the lumbar spine, total hip and femoral neck as well as levels of bone turnover markers [N-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase-5b (TRACP-5b)] were measured at years 1, 2, and 3. RESULTS The percent changes (Δ) in BMD values at years 1, 2, and 3 were as follows: RA group: 6.7 ± 6.2%, 8.9 ± 6.5%, and 9.8 ± 8.2% and PO group: 6.0 ± 4.8%, 8.9 ± 7.5%, and 12.6 ± 8.7% for the lumbar spine; RA group: 4.5 ± 4.6%, 5.2 ± 5.1%, and 6.8 ± 5.9% and PO group: 3.8 ± 4.5%, 4.6 ± 7.4%, and 6.8 ± 4.6% for the total hip; and RA group: 2.7 ± 5.1%, 4.1 ± 6.8%, and 4.3 ± 6.7% and PO group: 3.6 ± 8.0%, 4.5 ± 10.9%, and 5.7 ± 10.5% for the femoral neck, respectively. The ΔBMD for the lumbar spine, total hip, and femoral neck as well as ΔP1NP and ΔTRACP-5b did not differ significantly between the two groups at any time points. CONCLUSION Denosumab treatment for osteoporosis had a similar efficacy over 3 years among women with RA and PO. A better understanding of denosumab treatment for this patient population is important in clinical practice.
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Affiliation(s)
- Takeshi Mochizuki
- Department of Orthopaedic Surgery, Kamagaya General Hospital, Chiba, Japan
| | - Koichiro Yano
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsunori Ikari
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Ryo Hiroshima
- Department of Orthopaedic Surgery, Kamagaya General Hospital, Chiba, Japan
| | - Yuki Nasu
- Department of Orthopaedic Surgery, Kamagaya General Hospital, Chiba, Japan
| | - Ken Okazaki
- Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
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17
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Saeki C, Saito M, Oikawa T, Nakano M, Torisu Y, Saruta M, Tsubota A. Effects of denosumab treatment in chronic liver disease patients with osteoporosis. World J Gastroenterol 2020; 26:4960-4971. [PMID: 32952342 PMCID: PMC7476181 DOI: 10.3748/wjg.v26.i33.4960] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/03/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease (CLD) patients. Denosumab has been shown to increase bone mineral density (BMD) and decrease the risk of osteoporotic fracture in the general population. However, there are few reports evaluating the efficacy of denosumab in CLD patients.
AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.
METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo. The study period for evaluating efficacy and safety was 12 mo. Changes from baseline in BMD at the lumbar spine, femoral neck, and total hip were evaluated at 12 mo of denosumab treatment. Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b (bone resorption marker), serum total procollagen type I N-terminal propeptide (bone formation maker), and plasma pentosidine (bone quality marker).
RESULTS Among the 405 CLD patients, 138 (34.1%) patients were diagnosed with osteoporosis; among these, 78 patients met the exclusion criteria and thus 60 patients were finally included in the present study. The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine, femoral neck, and total hip were +4.44%, +3.71%, and +4.03%, respectively. Denosumab significantly improved BMD, regardless of sex, patient age, and presence of liver cirrhosis. Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment (P < 0.001). Plasma pentosidine levels were also significantly lower at 12 mo of treatment (P = 0.010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.
CONCLUSION Denosumab treatment was safe and increased BMD, suppressed bone turnover, and improved bone quality marker levels in CLD patients with osteoporosis, irrespective of differences in baseline characteristics.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Mitsuru Saito
- Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
| | - Akihito Tsubota
- Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 1058461, Japan
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18
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Davis S, Simpson E, Hamilton J, James MMS, Rawdin A, Wong R, Goka E, Gittoes N, Selby P. Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation. Health Technol Assess 2020; 24:1-314. [PMID: 32588816 PMCID: PMC7357239 DOI: 10.3310/hta24290] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. OBJECTIVES The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. DATA SOURCES For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. REVIEW METHODS A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. RESULTS Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. LIMITATIONS The incremental cost-effectiveness ratios are uncertain for very high-risk patients. CONCLUSIONS Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year. STUDY REGISTRATION This study is registered as PROSPERO CRD42018107651. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Sarah Davis
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Emma Simpson
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Jean Hamilton
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Marrissa Martyn-St James
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Andrew Rawdin
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Ruth Wong
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Edward Goka
- Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
| | - Neil Gittoes
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Peter Selby
- School of Medical Sciences, University of Manchester, Manchester, UK
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Botelho J, Machado V, Proença L, Delgado AS, Mendes JJ. Vitamin D Deficiency and Oral Health: A Comprehensive Review. Nutrients 2020; 12:E1471. [PMID: 32438644 PMCID: PMC7285165 DOI: 10.3390/nu12051471] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 12/15/2022] Open
Abstract
Vitamin D (VD) levels have been gaining growing attention in Oral Health. During growth and adulthood, VD deficiency (VDD) is associated with a wide variety of oral health disorders, and impaired VD synthesis may expedite some of these conditions. In children, severe VDD can induce defective tooth mineralization, resulting in dentin and enamel defects. As a consequence, these defects may increase the risk of the onset and progression of dental caries. Further, VDD has been associated with higher prevalence of periodontitis and gingival inflammation, and several recent preclinical and clinical studies have unveiled potential pathways through which Vitamin D may interact with the periodontium. VDD correction through supplementation may contribute to a successful treatment of periodontitis; however, alveolar bone regeneration procedures performed in baseline VDD patients seem more prone to failure. Vitamin D may also be linked with some oral pathology entities such as certain oral cancers and events of osteonecrosis of the jaw. This review aims to provide comprehensive evidence of how VD levels should be considered to promote good oral health, and to summarize how VDD may hamper oral development and its role in certain oral conditions.
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Affiliation(s)
- João Botelho
- Periodontology Department, Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal;
- CRU, CiiEM, Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal; (A.S.D.); (J.J.M.)
| | - Vanessa Machado
- Periodontology Department, Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal;
- CRU, CiiEM, Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal; (A.S.D.); (J.J.M.)
- Orthodontics Department, CRU, CiiEM, Egas Moniz–Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal
| | - Luís Proença
- Quantitative Methods for Health Research Unit (MQIS), CiiEM, Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal;
| | - Ana Sintra Delgado
- CRU, CiiEM, Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal; (A.S.D.); (J.J.M.)
- Orthodontics Department, CRU, CiiEM, Egas Moniz–Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal
| | - José João Mendes
- CRU, CiiEM, Egas Moniz—Cooperativa de Ensino Superior, 2829-511 Caparica, Almada, Portugal; (A.S.D.); (J.J.M.)
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Kunizawa K, Hiramatsu R, Hoshino J, Mizuno H, Ozawa Y, Sekine A, Kawada M, Sumida K, Hasegawa E, Yamanouchi M, Hayami N, Suwabe T, Sawa N, Ubara Y, Takaichi K. Denosumab for dialysis patients with osteoporosis: A cohort study. Sci Rep 2020; 10:2496. [PMID: 32051451 PMCID: PMC7016112 DOI: 10.1038/s41598-020-59143-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 01/24/2020] [Indexed: 11/22/2022] Open
Abstract
Evidence for the efficacy of denosumab in HD patients is limited. Accordingly, here we report a study on the safety and efficacy of denosumab in these patients. We prospectively followed 324 patients (121 HD and 203 non-HD patients) receiving denosumab between June 2013 and May 2018, assessing changes in bone mineral density (BMD) and bone metabolic markers, and noting side-effects. Annual changes in BMD at the lumbar spine in HD and non-HD patients from baseline were, respectively, 6.7 ± 11.1% and 7.5 ± 10.2% (p = 0.60), those at the femoral neck were 4.3 ± 7.9% and 3.1 ± 9.5% (p = 0.32), and those at the distal radius were −0.5 ± 6.4% and 0.2 ± 13.0% (p = 0.66). The prevalence of hypocalcemia (<8.5 mg/dL) was significantly higher in HD than in non-HD patients (35.6% vs 5.4%, p < 0.001). The median elapsed time between the first injection of denosumab and the occurrence of hypocalcemia was 7 days in HD patients. The decrease of serum calcium was greater in patients with higher TRACP5b, corticosteroid use, and those without CaCO3 supplementation. Our study suggests that denosumab was equally as effective in HD as non-HD patients. However, careful hypocalcemia monitoring, for at least 4 weeks, is recommended for HD patients.
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Affiliation(s)
- Kyohei Kunizawa
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.,Department of Nephrology, Kyorin University, Tokyo, Japan
| | | | - Junichi Hoshino
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan. .,Nephrology Center, Toranomon Hospital, Tokyo, Japan. .,The Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
| | | | - Yuko Ozawa
- Nephrology Center, Toranomon Hospital, Tokyo, Japan
| | | | | | - Keiichi Sumida
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | | | | | - Noriko Hayami
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | - Tatsuya Suwabe
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | - Naoki Sawa
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | - Yoshifumi Ubara
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.,The Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Kenmei Takaichi
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.,Nephrology Center, Toranomon Hospital, Tokyo, Japan.,The Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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21
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No impact of anti-Rank ligand and PTH analogs on cardiovascular risk in postmenopausal osteoporosis: a systematic literature review and meta-analysis. Arch Osteoporos 2020; 15:10. [PMID: 31897759 DOI: 10.1007/s11657-019-0672-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 11/14/2019] [Indexed: 02/03/2023]
Abstract
The mutual effects of drugs used in osteoporosis and cardiovascular diseases are a point of interest. A literature review and meta-analysis were conducted to address the impact of PTH analogs and anti-Rank ligand on cardiovascular events and overall mortality in individuals with idiopathic osteoporosis; these treatments do not appear to have any effect. INTRODUCTION Two meta-analyses have been conducted to explore the cardiovascular effects of bisphosphonates. There is no review for other osteoporosis treatments. A literature review and meta-analysis were conducted to address the impact of PTH analogs and anti-Rank ligand on cardiovascular events and overall mortality in individuals with idiopathic osteoporosis. METHODS A systematic review was conducted in December 2017 in the PubMed, Embase, and Cochrane databases and updated on PubMed in July 2019, selecting trials with a treatment and a control group. We also conducted a search for abstracts of the French Rheumatology Society, American College of Rheumatology, and European League Against Rheumatism's annual meetings over the past 4 years. The main endpoint was the occurrence of cardiovascular events; the secondary was mortality (all causes). RESULTS Of the 2782 reports initially found, 16 articles were used for the meta-analysis (6 for the anti-Rank ligand and 10 for the PTH analog group). After meta-analysis, there was no significant difference between the placebo group and the anti-Rank ligand group for overall mortality (p = 0.13), the combined endpoint (overall mortality, coronary artery disease, and stroke; p 0.77), and the individual risk of coronary artery disease (p 0.53), arrhythmia (p 0.95), and stroke (p 0.62). After meta-analysis, there was no significant difference between the placebo group and the PTH analogs group for overall mortality (p 0.77), the combined endpoint (p = 0.95), and the individual risk of coronary artery disease (p = 0.74), arrhythmia (p = 0.28), and stroke (p = 0.61). CONCLUSIONS The anti-Rank ligand and PTH analogs have no impact on cardiovascular risk and overall mortality in idiopathic osteoporosis. To better answer the question whether these treatments can reduce the long-term cardiovascular risk, further comparative studies with longer duration are required.
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22
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Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial. Blood Adv 2019; 2:2837-2847. [PMID: 30381400 DOI: 10.1182/bloodadvances.2018023085] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 08/16/2018] [Indexed: 12/20/2022] Open
Abstract
Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)-induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (-0.26% ± 5.31% vs -3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.
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23
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Naranjo Hernández A, Díaz del Campo Fontecha P, Aguado Acín MP, Arboleya Rodríguez L, Casado Burgos E, Castañeda S, Fiter Aresté J, Gifre L, Gómez Vaquero C, Candelas Rodríguez G, Francisco Hernández FM, Guañabens Gay N. Recomendaciones de la Sociedad Española de Reumatología sobre osteoporosis. ACTA ACUST UNITED AC 2019; 15:188-210. [DOI: 10.1016/j.reuma.2018.09.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 09/17/2018] [Accepted: 09/19/2018] [Indexed: 01/09/2023]
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Iwamoto N, Okamoto M, Tsuji S, Endo Y, Takatani A, Shimizu T, Umeda M, Fukui S, Sumiyoshi R, Igawa T, Koga T, Kawashiri SY, Aramaki T, Ichinose K, Tamai M, Nakamura H, Origuchi T, Eguchi K, Ueki Y, Kawakami A. Denosumab is effective toward glucocorticoid-induced osteoporosis patients complicated with rheumatic diseases regardless of prior anti-osteoporotic drugs. J Bone Miner Metab 2019; 37:554-562. [PMID: 30187273 DOI: 10.1007/s00774-018-0955-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 08/22/2018] [Indexed: 02/07/2023]
Abstract
We examined the efficacy and safety of denosumab as treatment for glucocorticoid-induced osteoporosis (GIOP) patients complicated with rheumatic diseases, by measuring patients' lumber bone mineral density (BMD) and bone turnover markers. A total of 66 consecutive patients for whom denosumab was initiated between July 2013 and August 2016 were enrolled and evaluated for 12 months. All of the patients were treated with glucocorticoids for underlying rheumatic diseases. The clinical assessment included measurements of the BMD of the lumbar spine (L2-L4) by a dual-energy X-ray absorptiometry technique and the bone turnover markers N-terminal telopeptide of type 1 collagen (NTX) in urine, serum intact procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) at baseline, 6 months and 12 months after the start of denosumab treatment. Adverse events (AEs) until 12 months were also analyzed. The mean percentage changes in BMD from baseline to 6 and 12 months were significant (2.85% increase, p < 0.0001 and 4.40% increase, p < 0.0001, respectively) regardless of the prior anti-osteoporotic drugs treatment (16 no transition from anti-osteoporotic drugs, 27 transition from bisphosphonate, 23 transition from teriparatide). The decreases in NTX, P1NP and BAP at 6 and 12 months were also significant. No serious AEs were noted. A multivariable logistic analysis showed that the prednisolone dose at baseline was associated with the clinical response to denosumab. In a real-world setting, denosumab was effective and safe for treating GIOP patients complicated with rheumatic diseases regardless of prior anti-osteoporotic drug treatment.
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Affiliation(s)
- Naoki Iwamoto
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Momoko Okamoto
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Sosuke Tsuji
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yushiro Endo
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ayuko Takatani
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Toshimasa Shimizu
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masataka Umeda
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Medical Education Development Center, Nagasaki University School Hospital, Nagasaki, Japan
| | - Shoichi Fukui
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Division of Advanced Preventive Medical Sciences, Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Remi Sumiyoshi
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takashi Igawa
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tomohiro Koga
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shin-Ya Kawashiri
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Division of Advanced Preventive Medical Sciences, Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | | | - Kunihiro Ichinose
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Mami Tamai
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Hideki Nakamura
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tomoki Origuchi
- Department of Physical Therapy, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Katsumi Eguchi
- Department of Rheumatology, Sasebo Chuo Hospital, Sasebo, Japan
| | - Yukitaka Ueki
- Department of Rheumatology, Sasebo Chuo Hospital, Sasebo, Japan
| | - Atsushi Kawakami
- Division of Advanced Preventive Medical Sciences, Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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25
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Zhang C, Zhang F, Liang G, Zeng X, Yu W, Jiang Z, Ma J, Zhao M, Xiong M, Gui K, Yuan F, Ji W. Denosumab versus zoledronic acid for preventing symptomatic skeletal events in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer: an outcome analyses with a mean follow-up of 3 years. BMC Musculoskelet Disord 2018; 19:424. [PMID: 30497434 PMCID: PMC6267057 DOI: 10.1186/s12891-018-2338-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 11/12/2018] [Indexed: 01/20/2023] Open
Abstract
Background The purpose of this study was to evaluate the efficacy of denosumab or zoledronic acid (ZA) using symptomatic skeletal events (SSEs) as the primary endpoint in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer. Methods Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer receiving subcutaneous denosumab 120 mg Q4W, or intravenous ZA 4 mg Q4W until the primary analysis cut-off date were retrospectively analysed in the Hong Kong Practice-Based Cancer Research Center(HKCRC) from March 2011 to March 2013. The time to first on-study SSE that was assessed either clinically or through routine radiographic scans was the primary endpoint. Results 242 patients received denosumab or ZA treatment (n = 120, mean age of 64.9 years (SD 3.01) and n = 122, 65.4 years (3.44), respectively). The median times to first on-study SSE were 14.7 months (12.9–45.6) and 11.7 months (9.9–45.6) for denosumab and ZA, respectively (hazard ratio, HR 0.44, 95% CI 0.71–2.95; p = 0·0002). Compared with the ZA group, denosumab-treated patients had a significantly delayed time to first SSE (HR 0.65 [95% CI 0.29–1.45], p < 0.0001). An increased incidence of SSE was found in the 16-month follow-up with rates of 2.1 and 10.7% for denosumab and ZA, respectively (P = 0.033). The difference persisted with time with rates of 8.3 and 17.2% at the final follow-up, respectively (P < 0.05). Conclusion In postmenopausal women aged ≥60 years with oestrogen-receptor-positive advanced breast cancer, denosumab significantly reduced the risk of developing SSEs compared with ZA. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.
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Affiliation(s)
- Chi Zhang
- Department of Joint surgery; Translational Research Centre of Regenerative Medicine and 3D Printing Technologies of Guangzhou Medical University, The Third Affiliated Hospital of Guangzhou Medical University, Duobao Road No.63, Liwan District, Guangzhou, 510150, Guangdong, China.
| | - Fan Zhang
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou, 510700, Guangdong, China.
| | - Guanzhao Liang
- Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No.183, Huangpu District, Guangzhou, 510700, Guangdong, China
| | - Xianshang Zeng
- Department of Orthopaedics, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou, 510700, Guangdong, China
| | - Weiguang Yu
- Department of Orthopaedics, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou, 510700, Guangdong, China
| | - Zhidao Jiang
- Department of breast surgery, Hongkong Elizabeth hospital, Gascoigne Road No.30, Kowloon, Hongkong, Kowloon, China
| | - Jie Ma
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Mingdong Zhao
- Department of Orthopaedics, Jinshan Hospital, Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai, 201508, China.
| | - Min Xiong
- Department of Orthopaedics, Jinshan Hospital, Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai, 201508, China
| | - Keke Gui
- Department of Orthopaedics, Jinshan Hospital, Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai, 201508, China
| | - Fenglai Yuan
- Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, 214041, Jiangsu, China.
| | - Weiping Ji
- Department of General Surgery, The second affiliated hospital and Yuying children's hospital of Wenzhou Medical University, Zhejiang, 325003, China
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Osteonecrosis of the jaw in patients treated with denosumab: A multicenter case series. J Craniomaxillofac Surg 2018; 46:1515-1525. [DOI: 10.1016/j.jcms.2018.05.046] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 05/11/2018] [Accepted: 05/24/2018] [Indexed: 01/22/2023] Open
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Abstract
Denosumab (Prolia®; Pralia®) is a human monoclonal antibody targeting the key bone resorption mediator RANKL. The drug is administered via subcutaneous injection once every 6 months and is approved for various indications, including the treatment of postmenopausal (PM) women with osteoporosis at increased/high risk of fracture or failure/intolerance of other osteoporosis therapies (indications featured in this review). Denosumab showed benefit in several phase 3 or 4 studies in PM women with osteoporosis or low bone mineral density (BMD), including the pivotal 3-year double-blind FREEDOM trial and its 7-year open-label extension. Denosumab reduced the risk of vertebral, nonvertebral and hip fractures and increased BMD across skeletal sites versus placebo in FREEDOM, with these benefits maintained over up to 10 years' therapy in the extension. The drug was also more effective in improving BMD than bisphosphonates, including in women switched from a bisphosphonate regimen, in 1-year trials; however, whether these differences translate into differences in anti-fracture efficacy is unclear. Denosumab was generally well tolerated over up to 10 years' treatment, although an increased risk of multiple vertebral fractures was observed after discontinuation of the drug. Thus, denosumab is a key treatment option for PM women with osteoporosis who have an increased/high risk of fracture or failure/intolerance of other osteoporosis therapies, although the potential for multiple vertebral fractures to occur after discontinuation of the drug requires consideration of subsequent management options.
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Affiliation(s)
- Emma D Deeks
- Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
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Suzuki T, Nakamura Y, Kato H. Vitamin D and Calcium Addition during Denosumab Therapy over a Period of Four Years Significantly Improves Lumbar Bone Mineral Density in Japanese Osteoporosis Patients. Nutrients 2018; 10:E272. [PMID: 29495518 PMCID: PMC5872690 DOI: 10.3390/nu10030272] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Revised: 02/13/2018] [Accepted: 02/23/2018] [Indexed: 01/22/2023] Open
Abstract
This study investigated whether or not vitamin D and calcium supplementation affected bone metabolism and bone mineral density (BMD) over a period of four years of denosumab therapy in patients with primary osteoporosis. Patients were divided into a denosumab monotherapy group (22 cases) or a denosumab plus vitamin D and calcium supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b, urinary N-terminal telopeptide of type-I collagen (NTX), and BMD of the lumbar 1-4 vertebrae (L-BMD) and bilateral hips (H-BMD) at baseline and at 12, 24, 36, and 48 months of treatment. There were no significant differences in patient background. Serum BAP, TRACP-5b, and urinary NTX were significantly and comparably inhibited in both groups from 12 to 48 months versus baseline values. L-BMD was significantly increased at every time point in both groups, while H-BMD was significantly increased at every time point in the combination group only. There were significant differences between the groups for L-BMD at 24, 36, and 48 months (P < 0.05) and for H-BMD at 12 months (P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab plus vitamin D and calcium significantly increased H-BMD at 12 months and L-BMD from 24 to 48 months. These findings indicate that continuous vitamin D and calcium supplementation is important, especially for 12 months to improve H-BMD and from 24 to 48 months to improve L-BMD.
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Affiliation(s)
- Takako Suzuki
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
| | - Yukio Nakamura
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
- Department of Orthopedic Surgery, Showa-Inan General Hospital, Akaho 3230, Komagane 399-4117, Japan.
| | - Hiroyuki Kato
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
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Sone T, Kon N, Gaither KW, Okubo N, Osakabe T, Nakayama Y, Fukunaga M, Ito M, Nakamura T. Effects of 3-year denosumab treatment on hip structure in Japanese postmenopausal women and men with osteoporosis. Bone Rep 2017; 7:164-171. [PMID: 29188222 PMCID: PMC5701790 DOI: 10.1016/j.bonr.2017.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 11/07/2017] [Accepted: 11/13/2017] [Indexed: 12/31/2022] Open
Abstract
Denosumab, a human monoclonal antibody against RANK ligand, is shown to have strong anti-fracture effects in Japanese osteoporosis patients. However, there have been no data showing actions on Japanese bone architecture. Here we show that denosumab continuously improves several geometrical parameters calculated by hip structural analysis for 3 years. Compared to placebo, denosumab significantly increased bone mineral density, cortical thickness and cross sectional area in all of the three analyzed areas: the narrow neck, intertrochanter and femoral shaft. The subsequent derived mechanical parameters, cross-sectional moment of inertia, section modulus and buckling ratio, were also improved by denosumab. In addition, the improvement of these parameters was also observed in the patients that had switched from placebo to denosumab treatment. The present study suggests the structural evidence explaining the strong anti-fracture efficacy of denosumab and its significant effects on cortical bone in Japanese.
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Key Words
- BMD, bone mineral density
- BR, buckling ratio
- Bone quality
- CSA, cross sectional area
- CSMI, cross sectional moment of inertia
- CoTh, cortical thickness
- DIRECT, Denosumab fracture Intervention Randomized placebo Controlled Trial
- DMAb/DMAb, denosumab/denosumab
- DXA, dual-energy X-ray absorptiometry
- Denosumab
- ED, endocortical diameter
- FREEDOM, Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months
- HSA, hip structural analysis
- Hip structural analysis
- Japanese
- OD, outer diameter
- Osteoporosis
- PBO/DMAb, placebo/denosumab
- RANK ligand
- RANK, receptor activator of nuclear factor kappa-B
- SM, section modulus
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Affiliation(s)
- Teruki Sone
- Department of Nuclear Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
| | - Naohiro Kon
- Medical Science Department, Daiichi Sankyo Co. Ltd., Tokyo, Japan
| | - Kenneth W. Gaither
- Bioclinica, Inc., 11731 Northeast Glenn Widing Drive Portland, Oregon 97220, United States
| | - Naoki Okubo
- Biostatistics and Data Management Department, Daiichi Sankyo Co. Ltd., Tokyo, Japan
| | - Taisuke Osakabe
- Clinical Development Department, Daiichi Sankyo Co. Ltd., Tokyo, Japan
| | - Yutaka Nakayama
- Post-Marketing Regulatory Affairs Department, Daiichi Sankyo Co. Ltd., Tokyo, Japan
| | - Masao Fukunaga
- Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
| | - Masako Ito
- Center for Diversity and Inclusion, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
| | - Toshitaka Nakamura
- Touto Sangenjaya Rehabilitation Hospital, 1-24-3 Sangenjaya, Setagaya-ku, Tokyo 154-0024, Japan
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Eudy-Byrne RJ, Gillespie W, Riggs MM, Gastonguay MR. A model of fracture risk used to examine the link between bone mineral density and the impact of different therapeutic mechanisms on fracture outcomes in patients with osteoporosis. J Pharmacokinet Pharmacodyn 2017; 44:599-609. [PMID: 29081020 DOI: 10.1007/s10928-017-9551-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 10/16/2017] [Indexed: 12/31/2022]
Abstract
A hazard model of fracture was developed using individual patient data (IPD) from the NHANES (2005-2008) database and summary-level data from an aggregate dataset (AD). The AD was built by performing a comprehensive and systematic literature search of clinical studies published from 1995 to 2015, recording fracture rate and bone mineral density (BMD) for both treatment and placebo arms. The search resulted in a metadata set comprised of 21 studies investigating the effects of various bisphosphonates, teriparatide, denosumab, and raloxifene in 65,254 patients over a cumulative 56.75 years of study. The IPD was used to augment an AD in a model-based meta-analysis (MBMA) hierarchical modeling approach. The resulting model predicts the probability of fracture events in patients with osteoporosis. The object of model building using this approach was to promote understanding of the impact of therapeutic drug effects on the probability of fracture together with, or independent of their effects on BMD. Candidate models were evaluated by deviance information criteria and posterior predictive check. The model with covariates for lumbar spine BMD with interaction with a drug effect on BMD, and patient body mass index, years post-menopause, fracture measure method (clinical or radiological) and an additional drug effect outperformed those models without interaction and without additional drug effects. The model quantitatively supports the widely held notion that changes in bone microarchitecture, which cannot be measured by areal BMD elicited by therapy contribute in a significant way to a reduction in fracture. Furthermore, this model can be used to simulate fracture risk in a clinical cohort similar to those contained in the MBMA.
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Affiliation(s)
- Rena J Eudy-Byrne
- Metrum Research Group, LLC, 2 Tunxis Road, Suite 112, Tariffville, CT, 06081, USA.
| | - William Gillespie
- Metrum Research Group, LLC, 2 Tunxis Road, Suite 112, Tariffville, CT, 06081, USA
| | - Matthew M Riggs
- Metrum Research Group, LLC, 2 Tunxis Road, Suite 112, Tariffville, CT, 06081, USA
| | - Marc R Gastonguay
- Metrum Research Group, LLC, 2 Tunxis Road, Suite 112, Tariffville, CT, 06081, USA
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Nakamura Y, Suzuki T, Kamimura M, Murakami K, Ikegami S, Uchiyama S, Kato H. Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment. Bone Res 2017; 5:17021. [PMID: 29021920 PMCID: PMC5634512 DOI: 10.1038/boneres.2017.21] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Revised: 01/15/2017] [Accepted: 02/15/2017] [Indexed: 01/15/2023] Open
Abstract
To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group (18 cases) or a denosumab plus vitamin D supplementation group (combination group; 23 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density (BMD) of L1–4 lumbar vertebrae (L)-BMD and bilateral hips (H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months (except at 12 months for NTX). In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months (P<0.05). BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and 12 months (8.9%) in the combination group and at 4, 8 and 12 months (6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group (3.6%) compared with the denosumab group (1.2%) at 12 months (P<0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD (especially at the hips).
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Affiliation(s)
- Yukio Nakamura
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.,Department of Orthopedic Surgery, Showa-Inan General Hospital, Komagane, Japan
| | - Takako Suzuki
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Mikio Kamimura
- Center of Osteoporosis and Spinal Disorders, Kamimura Orthopaedic Clinic, Matsumoto, Japan
| | - Kohei Murakami
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shota Ikegami
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shigeharu Uchiyama
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroyuki Kato
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
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What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A systematic review. J Craniomaxillofac Surg 2017; 45:1493-1502. [DOI: 10.1016/j.jcms.2017.05.028] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 05/03/2017] [Accepted: 05/29/2017] [Indexed: 01/12/2023] Open
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Ebina K, Kashii M, Hirao M, Hashimoto J, Noguchi T, Koizumi K, Kitaguchi K, Matsuoka H, Iwahashi T, Tsukamoto Y, Yoshikawa H. Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis. J Bone Miner Metab 2017; 35:571-580. [PMID: 27830384 DOI: 10.1007/s00774-016-0792-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 09/20/2016] [Indexed: 01/22/2023]
Abstract
The aim of this 12-month, retrospective study was to compare the effects of denosumab (DMAb; 60 mg subcutaneously every 6 months) plus native vitamin D (VD) (cholecalciferol) combination therapy with DMAb plus active VD analog (alfacalcidol) combination therapy in patients with postmenopausal osteoporosis. Patients [N = 127; mean age 75.6 years (range 58-93 years); 28 treatment-naïve patients, 59 patients treated with oral bisphosphonate therapy, 40 patients treated with teriparatide daily] were allocated to either (1) the DMAb plus native VD group (n = 60; cholecalciferol, 10 μg, plus calcium, 610 mg/day; 13 treatment-naïve patients, 28 patients treated with oral bisphosphonate therapy, and 19 patients treated with teriparatide daily) or (2) the DMAb plus active VD group [n = 67; alfacalcidol, 0.8 ± 0.0 μg, plus calcium, 99.2 ± 8.5 mg/day; 15 treatment-naïve patients, 31 patients treated with oral bisphosphonate therapy, and 21 patients treated with teriparatide daily) on the basis of each physician's decision. Changes in bone mineral density (BMD), serum bone turnover marker levels, and fracture incidence were monitored every 6 months. There were no significant differences in baseline age, BMD, bone turnover marker levels, and prior treatments between the two groups. After 12 months, compared with the DMAb plus native VD group, the DMAb plus active VD group showed similar increases in the BMD of the lumbar spine (6.4% vs 6.5%) and total hip (3.3% vs 3.4%), but significantly greater increases in the BMD of the femoral neck (1.0% vs 4.9%, P < 0.001) and the distal part of the forearm (third of radius) (-0.8% vs 3.9%, P < 0.01). These tendencies were similar regardless of the differences in the prior treatments. The rates of decrease of bone turnover marker levels were similar for tartrate-resistant acid phosphatase isoform 5b (-49.0% vs -49.0%), procollagen type I N-terminal propeptide (-45.9% vs -49.3%), and undercarboxylated osteocalcin (-56.0 vs -66.5%), whereas serum intact parathyroid hormone levels were significantly lower in the DMAb plus active VD group (47.6 pg/mL vs 30.4 pg/mL, P < 0.001). The rate of hypocalcemia was 1.7% in the DMAb plus native VD group and 1.5% in the DMAb plus active VD group, and the rate of clinical fracture incidence was 8.3% in the DMAb plus native VD group and 4.5% in the DMAb plus active VD group, with no significant difference between the groups. DMAb with active VD combination therapy may be a more effective treatment option than DMAb with native VD combination therapy in terms of increasing BMD of the femoral neck and distal part of the forearm and also maintaining serum intact parathyroid hormone at lower levels.
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Affiliation(s)
- Kosuke Ebina
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Masafumi Kashii
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Hirao
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Jun Hashimoto
- Department of Rheumatology, National Hospital Organization, Osaka Minami Medical Center, 2-1 Kidohigashi, Kawachinagano, Osaka, 586-8521, Japan
| | - Takaaki Noguchi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kota Koizumi
- Department of Orthopaedic Surgery, Japan Community Health Care Organization, Osaka Hospital, 4-2-78 Fukushima Ward, Osaka, 586-8521, Japan
| | - Kazuma Kitaguchi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hozo Matsuoka
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Toru Iwahashi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasunori Tsukamoto
- Department of Orthopaedic Surgery, North Osaka Police Hospital, 1-2-2 Muroyama, Ibaraki, Osaka, 567-0052, Japan
| | - Hideki Yoshikawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Suzuki T, Nakamura Y, Kato H. Changes of Bone-Related Minerals during Denosumab Administration in Post-Menopausal Osteoporotic Patients. Nutrients 2017; 9:nu9080871. [PMID: 28805705 PMCID: PMC5579664 DOI: 10.3390/nu9080871] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 07/19/2017] [Accepted: 08/08/2017] [Indexed: 12/28/2022] Open
Abstract
Objectives: This retrospective study included 21 patients with primary osteoporosis who were treated with the anti-resorption drug, denosumab. To date, there has been no detailed report on the changes of bone-related minerals after anti-resorption drug therapy. Methods: Twenty-one post-menopausal females were retrospectively enrolled. Serum zinc (Zn), magnesium (Mg), iron (Fe), copper (Cu), grip strength, and estimated glomerular filtration rate (eGFR) were examined at one week and 1, 2, 4, 6, 8, 10, and 12 months. Lumbar spine (L1-4) bone mineral density (L-BMD) and bilateral total hip BMD (H-BMD) were examined before and at 4, 8, and 12 months after treatment commencement. Results: Serum Zn tended to decrease at one week and one month, and tended to increase during 10 to 12 months. Serum Cu maintained during zero to eight months, then decreased at 10 and 12 months. Serum Fe gradually increased after four months. Serum Mg sharply increased at one week, then decreased further. Grip strength increased for two months, then slightly decreased and maintained 4 to 12 months. eGFR almost maintained for zero to eight months, then slightly decreased thereafter. L-BMD values significantly increased at eight (5.8%) (p < 0.01) and 12 months (9.8%) (p < 0.01). H-BMD increased during the period (at 12 months: 3.7%). Conclusions: These results suggest that at later phases of denosumab therapy, Zn and Fe tended to increase while Mg tended to decrease, all of which are important for bone metabolism. Thus, denosumab might improve Zn and Fe metabolism, and thereby likely increase BMD. Since denosumab may not improve Mg, it is better to obtain Mg supplementation during the therapy.
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Affiliation(s)
- Takako Suzuki
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
| | - Yukio Nakamura
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
- Department of Orthopedic Surgery, Showa-Inan General Hospital, Akaho 3230, Komagane 399-4117, Japan.
| | - Hiroyuki Kato
- Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
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Nakamura Y, Suzuki T, Yoshida T, Yamazaki H, Kato H. Vitamin D and Calcium Are Required during Denosumab Treatment in Osteoporosis with Rheumatoid Arthritis. Nutrients 2017; 9:nu9050428. [PMID: 28445420 PMCID: PMC5452158 DOI: 10.3390/nu9050428] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 04/16/2017] [Accepted: 04/21/2017] [Indexed: 12/16/2022] Open
Abstract
The aim of this 12-month retrospective study was to evaluate differences in the outcomes of denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients having osteoporosis (OP) with rheumatoid arthritis (RA). Patients were divided into the denosumab monotherapy group (denosumab group, 22 cases) or denosumab plus vitamin D supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), N-terminal propeptide of type 1 collagen (P1NP), tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, and 1, 2, 4, 6, 8, and 12 months. We also assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) at baseline and 4, 8, and 12 months. Matrix metalloprotanase-3 (MMP-3), Disease Activity Score-28 C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI), and Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed before treatment and at 12 months to evaluate RA conditions. The study results showed that BAP, TRACP-5b, and NTX were significantly decreased, but tended to return to pre-treatment levels around 6 and 12 months in both groups. While L-BMD and H-BMD substantially increased in both groups, H-BMD had become significantly higher in the combination group at 12 months (p < 0.01) as compared with the denosumab group. There were no significant differences between the groups regarding MMP-3, DAS28-CRP, SDAI, or HAQ-DI. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium significantly increased H-BMD in patients having OP with RA.
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Affiliation(s)
- Yukio Nakamura
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
| | - Takako Suzuki
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
| | - Tomohiko Yoshida
- Department of Rheumatology, Toshin Yoshida Internal Medicine, Gomyo 643-2, Sakaki-Machi 389-0606, Japan.
| | - Hideshi Yamazaki
- Department of Rheumatology, Marunouchi Hospital, Nagisa 1-7-45, Matsumoto 390-8601, Japan.
| | - Hiroyuki Kato
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
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Taguchi A, Shiraki M, Morrison A, Khan AA. Antiresorptive agent-related osteonecrosis of the jaw in osteoporosis patients from Asian countries. Osteoporos Sarcopenia 2017; 3:64-74. [PMID: 30775507 PMCID: PMC6372774 DOI: 10.1016/j.afos.2017.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 02/27/2017] [Accepted: 03/04/2017] [Indexed: 11/05/2022] Open
Abstract
Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) was first reported in oncology patients in 2003 and subsequently in osteoporosis patients in 2004. Since oral surgical procedures, such as tooth extraction, are also considered one of the major risk factors for ONJ, there is confusion among physicians, dentists, and patients—particularly osteoporosis patients currently taking BPs—regarding the safety of remaining on therapy surrounding these procedures. Many papers about BP-related ONJ (BRONJ) have been published to date. In addition to BRONJ, recent studies have reported an association between ONJ and the antiresorptive therapy denosumab (Dmab; a RANKL-inhibitor). BRONJ and Dmab-related ONJ are together referred to as antiresorptive agent-related ONJ (ARONJ). The pathogenesis of ARONJ still remains unknown. It is forecasted that there will be an increased incidence of patients with osteoporotic fractures and an increased number of prescriptions for antiresorptive agents in Asia in the future. However, prescriptions for antiresorptives for osteoporosis may be restricted in the Asian population as the occurrence of ARONJ may be higher as compared with those in other countries. In this review, we focused on the following topics as it pertains to the Asian osteoporotic population: the oral condition specific for osteoporosis patients; definition, staging, prevalence and incidence of ARONJ; imaging modalities for ARONJ; specific risk factors for ARONJ; prevention strategies for ARONJ, and; cooperation between physicians and dentists in the prevention of ARONJ. Ideally, the Asian Federation of Osteoporosis Societies would cooperate with one another and find more population-specific evidence for the prevention of ARONJ.
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Affiliation(s)
- Akira Taguchi
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Matsumoto Dental University, Shiojiri, Japan
| | - Masataka Shiraki
- Research Institute and Practice for Involutional Diseases, Nagano, Japan
| | | | - Aliya A Khan
- Divisions of Endocrinology and Metabolism and Geriatrics, Department of Medicine, McMaster University, Hamilton, ON, Canada
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Nakatoh S. Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change. Osteoporos Sarcopenia 2017; 3:45-52. [PMID: 30775502 PMCID: PMC6372821 DOI: 10.1016/j.afos.2016.12.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 12/09/2016] [Accepted: 12/13/2016] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES This study aimed to investigate the correlation between bone mineral density (BMD) and the turnover rate [√(MoMf2 + MoMr2), multiple of median formation (MoMf) was calculated as bone-specific alkaline phosphatase (BAP) value/18.6 and multiple of median resorption (MoMr) as tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463] and the balance (MoMf/MoMr) and to compare differences in therapeutic effects evoked by differences in previous treatments. METHODS In 51 osteoporotic women treated with bisphosphonates (BPs) or selective estrogen receptor modulators (SERMs), BMD was measured at 0, 24, and 48 weeks after denosumab administration. The values of BAP and TRACP-5b were measured at 0, 4, 12, 24, 36, and 48 weeks. RESULTS The turnover rate decreased at week 4 and decreased further at week 12. The balance indicated a relative predominantly formative state at week 4. This balance became higher in the SERM group than in the BP group at week 4. A correlation was observed between the rate of BMD change and turnover rate at weeks 0 and 4. CONCLUSIONS It is necessary to evaluate the turnover rate and balance to determine the therapeutic effect of denosumab, which induces dissociation between the trends in the bone turnover markers. Turnover rate and balance during the early stages of denosumab treatment may be predictive factors of BMD. When switching from bone resorption inhibitors to denosumab, it was necessary to consider the beginning values that were affected by the previous treatment. The state of relative anabolism is greater at 4 weeks when the previous treatment involved SERMs rather than BPs.
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Affiliation(s)
- Shinichi Nakatoh
- Department of Orthopedic Surgery, Asahi General Hospital, 477 Tomari, Asahimachi, Toyama 939-0741, Japan
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Baum R, Gravallese EM. Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts. Clin Rev Allergy Immunol 2017; 51:1-15. [PMID: 26411424 DOI: 10.1007/s12016-015-8515-6] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Dysregulated bone remodeling occurs when there is an imbalance between bone resorption and bone formation. In rheumatic diseases, including rheumatoid arthritis (RA) and seronegative spondyloarthritis, systemic and local factors disrupt the process of physiologic bone remodeling. Depending upon the local microenvironment, cell types, and local mechanical forces, inflammation results in very different effects on bone, promoting bone loss in the joints and in periarticular and systemic bone in RA and driving bone formation at enthesial and periosteal sites in diseases such as ankylosing spondylitis (AS), included within the classification of axial spondyloarthritis. There has been a great deal of interest in the role of osteoclasts in these processes and much has been learned over the past decade about osteoclast differentiation and function. It is now appreciated that osteoblast-mediated bone formation is also inhibited in the RA joint, limiting the repair of erosions. In contrast, osteoblasts function to produce new bone in AS. The Wnt and BMP signaling pathways have emerged as critical in the regulation of osteoblast function and the outcome for bone in rheumatic diseases, and these pathways have been implicated in both bone loss in RA and bone formation in AS. These pathways provide potential novel approaches for therapeutic intervention in diseases in which inflammation impacts bone.
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Affiliation(s)
- Rebecca Baum
- Department of Medicine and Division of Rheumatology, University of Massachusetts Medical School, Lazare Research Building Suite 223, 364 Plantation Street, Worcester, MA, 01605, USA
| | - Ellen M Gravallese
- Department of Medicine and Division of Rheumatology, University of Massachusetts Medical School, Lazare Research Building Suite 223, 364 Plantation Street, Worcester, MA, 01605, USA.
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Yoneda T, Hagino H, Sugimoto T, Ohta H, Takahashi S, Soen S, Taguchi A, Nagata T, Urade M, Shibahara T, Toyosawa S. Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw. J Bone Miner Metab 2017; 35:6-19. [PMID: 28035494 DOI: 10.1007/s00774-016-0810-7] [Citation(s) in RCA: 177] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Accepted: 12/04/2016] [Indexed: 01/12/2023]
Abstract
Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.
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Affiliation(s)
- Toshiyuki Yoneda
- Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, USA.
- The Japanese Society for Bone and Mineral Research, Kyoto, Japan.
| | - Hiroshi Hagino
- School of Health Science, Faculty of Medicine, Tottori University, Tottori, Japan
- The Japanese Society for Bone and Mineral Research, Kyoto, Japan
| | - Toshitsugu Sugimoto
- Internal Medicine 1, Shimane University Faculty of Medicine, Matsue, Japan
- The Japanese Society for Bone and Mineral Research, Kyoto, Japan
| | - Hiroaki Ohta
- Clinical Research Centers for Medicine, International University of Health and Welfare, Ohtawara, Japan
- The Japan Osteoporosis Society, Tokyo, Japan
| | - Shunji Takahashi
- Department of Medical Oncology, The Cancer Institute Hospital Of Japanese Foundation of Cancer Research, Tokyo, Japan
- The Japanese Society for Bone and Mineral Research, Kyoto, Japan
| | - Satoshi Soen
- Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan
- The Japan Osteoporosis Society, Tokyo, Japan
| | - Akira Taguchi
- Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan
- The Japanese Society of Oral and Maxillofacial Radiology, Tokyo, Japan
| | - Toshihiko Nagata
- Department of Periodontology and Endodontology, School of Dentistry, Tokushima University, Tokushima, Japan
- The Japanese Society of Periodontology, Tokyo, Japan
| | - Masahiro Urade
- Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Japan
- The Japanese Society of Oral and Maxillofacial Surgeons, Tokyo, Japan
| | - Takahiko Shibahara
- Department of Oral and Maxillo-Facial Surgery, Tokyo Dental College, Tokyo, Japan
- The Japanese Society of Oral and Maxillofacial Surgeons, Tokyo, Japan
| | - Satoru Toyosawa
- Department of Oral Pathology, Osaka University Graduate School of Dentistry, Suita, Japan
- The Japanese Society of Oral Pathology, Tokyo, Japan
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Ebina K, Hashimoto J, Kashii M, Hirao M, Kaneshiro S, Noguchi T, Tsukamoto Y, Yoshikawa H. The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis. J Bone Miner Metab 2017; 35:91-98. [PMID: 26762133 DOI: 10.1007/s00774-015-0731-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 12/03/2015] [Indexed: 01/21/2023]
Abstract
The aim of this 12-month, observational study was to compare the effects of switching daily teriparatide (TPTD) to oral bisphosphonates (BP) therapy or denosumab (DMAb) therapy in patients with primary osteoporosis. Patients [n = 78; 71 postmenopausal women and seven men; mean age 76.3 (64-94) years; mean duration of prior daily TPTD therapy 20.1 (6-24) months] were allocated to either the (1) "switch-to-BP" group [n = 36; weekly alendronate 35 mg (n = 19), weekly risedronate 17.5 mg (n = 12), monthly minodronate 50 mg (n = 5)]; or (2) "switch-to-DMAb" group (n = 42; 60 mg sc every 6 months) based on each physicians' decision. Changes in bone mineral density (BMD) and serum bone turnover markers were monitored every 6 months. No significant difference was observed in baseline clinical characteristics between the groups. After 12 months, the increase in BMD was significantly greater in the switch-to-DMAb group compared to the switch-to-BP group: lumbar spine (6.2 vs. 2.6 %; P < 0.01), total hip (4.2 vs. 1.1 %; P < 0.05), and femoral neck (3.5 vs. 1.4 %; P < 0.05). In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (-55.8 vs. -32.8 %; P < 0.01) and ucOC (-85.5 vs. -65.0 %; P < 0.001), while no significant difference was observed in PINP (-67.5 vs. -62.1 %). Switching daily TPTD to DMAb significantly increased BMD and decreased bone resorption marker compared to switching to oral BP at 12 months, and thus may provide an effective sequential treatment option after daily TPTD treatment.
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Affiliation(s)
- Kosuke Ebina
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Jun Hashimoto
- Department of Rheumatology, National Hospital Organization, Osaka Minami Medical Center, 2-1 Kidohigashi, Kawachinagano, Osaka, 586-8521, Japan
| | - Masafumi Kashii
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Hirao
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shoichi Kaneshiro
- Department of Orthopaedic Surgery, Japan Community Health Care Organization, Osaka Hospital, 4-2-78 Fukushima Ward, Osaka, 586-8521, Japan
| | - Takaaki Noguchi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasunori Tsukamoto
- Department of Orthopaedic Surgery, North Osaka Police Hospital, 1-2-2 Muroyama, Ibaraki, Osaka, 567-0052, Japan
| | - Hideki Yoshikawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, Janos B, Ruff VA. Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study. J Clin Endocrinol Metab 2016; 101:1353-63. [PMID: 26859106 PMCID: PMC4880160 DOI: 10.1210/jc.2015-4181] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab.
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Affiliation(s)
- David W Dempster
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Hua Zhou
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Robert R Recker
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Jacques P Brown
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Christopher P Recknor
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - E Michael Lewiecki
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Paul D Miller
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Sudhaker D Rao
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - David L Kendler
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Robert Lindsay
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - John H Krege
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Jahangir Alam
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Kathleen A Taylor
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Boris Janos
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
| | - Valerie A Ruff
- Regional Bone Center (D.W.D., H.Z., R.L.), Helen Hayes Hospital, West Haverstraw, New York; Department of Pathology and Cell Biology (D.W.D.), College of Physicians and Surgeons of Columbia University, New York; Department of Medicine (R.R.R.), Division of Endocrinology, School of Medicine, Creighton University, Omaha, Nebraska; Rheumatology and Bone Diseases Research Group (J.P.B.), CHU de Quebec (CHUL) Research Centre and Department of Medicine, Laval University, Quebec City, Quebec, Canada; United Osteoporosis Centers (C.P.R.), Gainesville, Georgia; New Mexico Clinical Research & Osteoporosis Center (E.M.L.), Albuquerque, New Mexico; Department of Medicine (P.D.M.), Colorado Center for Bone Research, Lakewood, Colorado; Bone & Mineral Research Laboratory (S.D.R.), Henry Ford Hospital, Detroit, Michigan; Department of Medicine (Endocrinology) (D.L.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine (R.L.), College of Physicians and Surgeons of Columbia University, New York; Lilly Research Laboratories (J.H.K., J.A.), Eli Lilly and Company, Indianapolis, Indiana; Musculoskeletal and Men's Health (K.A.T., V.A.R.), Lilly USA, LLC, Indianapolis, Indiana; Research and Development - Bio-Medicines (B.J.), Eli Lilly Canada Inc., Toronto, Ontario, Canada
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42
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Bagan J, Peydró A, Calvo J, Leopoldo M, Jiménez Y, Bagan L. Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis. Oral Dis 2016; 22:324-9. [PMID: 26818808 DOI: 10.1111/odi.12447] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 01/05/2016] [Accepted: 01/16/2016] [Indexed: 01/22/2023]
Abstract
OBJECTIVE To describe the clinical characteristics and evolution of our series of medication-related osteonecrosis of the jaws (MRONJ) associated with denosumab in osteoporotic patients. MATERIAL AND METHODS We present 10 new cases of MRONJ in patients receiving denosumab for osteoporosis. We describe the mean doses of denosumab, previous bisphosphonate intake, and the clinical characteristics associated with the osteonecrosis, such as local contributing factors, symptoms, and evolution after treatment. RESULTS The mean number of denosumab doses was 3.4 ± 2.2. In 90% of patients, there was a prior history of oral bisphosphonate intake, with a mean duration of 46.78 ± 25.11 months. The most common local factor was dental extraction (6 cases; 60%), and most cases had necrotic bone exposure (9/10, 90%). Sclerosis of the bone was the most common radiographic finding. Stage 1 was the most common ONM stage, found in 80%. 'Cure' after conservative treatments was obtained in 71.4%. CONCLUSIONS Most of our cases were in the early stages of MRONJ, and the success rate after conservative treatment was high.
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Affiliation(s)
- J Bagan
- Oral Medicine, University of Valencia, Valencia, Spain.,Service of Stomatology and Maxillofacial Surgery, University General Hospital, Valencia, Spain
| | - A Peydró
- Oral Medicine, Valencia University, Valencia, Spain
| | - J Calvo
- Rheumatology, University General Hospital, Valencia, Spain
| | - M Leopoldo
- Service of Stomatology and Maxillofacial Surgery, University General Hospital, Valencia, Spain
| | - Y Jiménez
- Oral Medicine, Valencia University, Valencia, Spain
| | - L Bagan
- Oral Medicine, Universidad Europea Valencia, Valencia, Spain
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43
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Dodson TB. The Frequency of Medication-related Osteonecrosis of the Jaw and its Associated Risk Factors. Oral Maxillofac Surg Clin North Am 2015; 27:509-16. [PMID: 26362367 DOI: 10.1016/j.coms.2015.06.003] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
This article provides the best current frequency estimate of medication-related osteonecrosis of the jaws (MRONJ), and identifies factors associated with the risk of developing osteonecrosis of the jaw (ONJ) among patients exposed to relevant medications (ie, antiresorptive or antiangiogenic agents). MRONJ is a rare but serious complication of cancer treatment or osteoporosis management. This review confirms that antiresorptive medications such as oral or intravenous bisphosphonates and denosumab are the most common risk factors for developing ONJ. The risk of MRONJ is greater in patients with cancer than in those receiving antiresorptive treatments for osteoporosis by a factor of 10.
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Affiliation(s)
- Thomas B Dodson
- Department of Oral and Maxillofacial Surgery, University of Washington School of Dentistry, 1959 Northeast Pacific Street, Health Sciences Building B-241, Box 357134, Seattle, WA 98195-7134, USA.
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