-
1.
Analysis of the Mechanism and Safety of Bisphosphonates in Patients with Lung Cancer and Bone Metastases.
Zhang, G, Gong, H, Xu, H
Computational and mathematical methods in medicine. 2021;:5343104
Abstract
OBJECTIVE To explore the mechanism and safety of bisphosphonates in patients with lung cancer and bone metastases. METHOD A total of 104 patients with lung cancer and bone metastases in our hospital were selected and randomly divided into two groups: control group (n = 54) and research group (n = 50). Chemotherapy was given to the control group, and the research group was treated with bisphosphonate drugs. The quality of life, HAMA, HAMD score, VAS score, treatment effect, serum calcium and KPS score, inflammatory factor levels, and immune function were compared between the two groups. RESULT The quality of life in both groups was significantly increased (P < 0.05). The HAMA and HAMD scores of the research group decreased significantly than those of the control group after treatment (P < 0.05). The VAS scores of the two groups were significantly reduced (P < 0.05). The effective rates of treatment in the control group and the research group were 81.5% and 96.0%, respectively. Serum calcium was significantly decreased, and KPS score was significantly increased at weeks 1 and 6 after treatment, and the change was more obvious in the research group (P < 0.05). The levels of inflammatory factors in the two groups were significantly reduced, and the immune indicators were significantly increased. CONCLUSION Bisphosphonates have good effect on patients with lung cancer and bone metastases, which can improve anxiety and depression, reduce pain score, improve serum calcium level and immune function, and reduce inflammatory response. Therefore, bisphosphonate drug therapy is worth widely used.
-
2.
Bone-modifying Agents (BMAs) in Breast Cancer.
Shapiro, CL
Clinical breast cancer. 2021;(5):e618-e630
Abstract
Bone-modifying agents (BMAs) are mainstays in breast cancer and prevent and treat osteoporosis in early-stage disease and reduce skeletal metastases complications in advanced disease. There is some evidence to support that BMA also prevents skeletal metastases and improves overall survival. Bone loss occurs with chemotherapy-induced ovarian failure, gonadotrophin-releasing hormone (GnRH) agonists, and aromatase inhibitors. In some women, the bone loss will be of sufficient magnitude to increase the risks of osteoporosis or fractures. Recommended steps in osteoporosis prevention or treatment include risk factor assessment, taking adequate amounts of calcium and vitamin D3, and periodic evaluations with dual-energy x-ray absorptiometry scanning. If clinically indicated by the T-scores and fracture-risk prediction algorithms treat with oral, IV bisphosphonates or subcutaneous denosumab (DEN). Zoledronic acid (ZA) or DEN reduces skeletal metastases complications, including pathological fracture, spinal cord compression, or the necessity for radiation or surgery to bone. Also, both of these drugs have the side-effect of osteonecrosis at a similar incidence. Monthly administration of ZA or DEN is standard, but several recent randomized trials show noninferiority between ZA monthly and every 3-month ZA. Every 3-month ZA is a new standard of care. Similar trials of the schedule of DEN are ongoing. ZA anticancer effect is only in postmenopausal women or premenopausal women rendered postmenopausal by GnRH agonists or bilateral oopherectomy. High-risk women, either postmenopausal or premenopausal, receiving GnRH/oopherctomy should consider adjuvant ZA. There are insufficient data to support DEN in this setting. Herein, this narrative review covers the mechanism of action of BMA, randomized clinical trials, and adverse events, both common and rare.
-
3.
Role of Bisphosphonates in The Prevention of Postoperative Hungry Bone Syndrome in Primary Hyperparathyroidism: A Meta-Analysis and Need for Randomized Controlled Trials.
Pal, R, Gautam, A, Bhadada, SK
Drug research. 2021;(2):108-109
Abstract
Dear Editor,Hungry bone syndrome (HBS) is a clinico-biochemical entity characterized by the development of profound and prolonged hypocalcemia associated with hypophosphatemia, hypomagnesemia, and rising alkaline phosphatase which follows curative parathyroidectomy for severe primary and secondary hyperparathyroidism. The prevalence of HBS after parathyroidectomy in primary hyperparathyroidism (PHPT) is variable with several case series from Asia reporting remarkably higher prevalence rates of 24-87% 1.
-
4.
Bisphosphonate Therapy for Treating Osteonecrosis in Pediatric Leukemia Patients: A Systematic Review.
Daneshdoost, SM, El Abiad, JM, Ruble, KJ, Jones, LC, Crane, JL, Morris, CD, Levin, AS
Journal of pediatric hematology/oncology. 2021;(3):e365-e370
-
-
Free full text
-
Abstract
BACKGROUND Despite improved outcomes in children with leukemia, complications such as osteonecrosis are common. We conducted a systematic review to investigate the role of bisphosphonates in reducing pain, improving mobility, and stabilizing lesions in pediatric leukemia survivors. METHODS Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, Cochrane, Web of Science, Scopus, CINAHL, and ClinicalTrials.gov databases. Five of 221 articles retrieved met our inclusion criteria. RESULTS Bisphosphonates, especially when combined with dietary calcium and vitamin D supplements and physical therapy (supplements/PT) were associated with improved pain and mobility in 54% and 50% of patients, respectively. A significantly greater proportion of patients treated with bisphosphonates (83%) reported mild/moderate pain or no pain compared with those with supplements/PT alone (36%) (P<0.001). Sixty-six percent of patients treated with bisphosphonates achieved improved/full mobility compared with 27% of those treated with supplements/PT alone (P=0.02). However, 46% of patients showed progressive joint destruction despite bisphosphonate therapy. No adverse events were reported, except for acute phase reactions to intravenous therapies. CONCLUSIONS Bisphosphonates, when combined with supplements/PT, were associated with less pain and improved mobility, but not prevention of joint destruction in pediatric leukemia patients with osteonecrosis.
-
5.
Bisphosphonate use in children with cerebral palsy.
Hurley, T, Zareen, Z, Stewart, P, McDonnell, C, McDonald, D, Molloy, E
The Cochrane database of systematic reviews. 2021;(7):CD012756
-
-
Free full text
-
Abstract
BACKGROUND Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA All relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta-analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS We found two relevant RCTs (34 participants). Both studies included participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. PRIMARY OUTCOME Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post-intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post-intervention in lumbar spine z-score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). SECONDARY OUTCOMES Very low certainty evidence from one study found that bisphosphonate reduced serum N-telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone-specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight-bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.
-
6.
Bisphosphonate and denosumab initiation in older adults in Ontario, Canada: a population-based cohort study.
Clemens, KK, Jeyakumar, N, Ouédraogo, AM, Thain, J, Khan, T
Archives of osteoporosis. 2020;(1):133
Abstract
UNLABELLED We provide an update on how commonly prescribed osteoporosis therapies are being initiated in older adults in Ontario. Patients newly prescribed denosumab are older, more often female, and have more comorbidities than those prescribed bisphosphonates. Their characteristics, monitoring, and persistence with prescribed therapy differ from clinical trial participants. Real-world studies on oral bisphosphonates and denosumab might be valuable. PURPOSE To provide a contemporary view on oral bisphosphonate and denosumab prescribing to older adults in routine care. METHODS Using linked healthcare databases, we conducted a population-based cohort study of adults ≥ 66 years newly prescribed oral bisphosphonates or denosumab between February 2013 and March 2017 in Ontario, Canada. We captured their clinical characteristics, monitoring, and continuous use of prescribed therapies. We illustrate how "real-world" new users of bisphosphonates and denosumab differ from randomized controlled trial (RCT) participants. RESULTS There were 107,847 individuals newly prescribed oral bisphosphonates (n = 59,996) or denosumab (n = 47,851) over the study period. Compared with new users of oral bisphosphonates, denosumab users were older (mean age 79.1 vs. 75.7 years), more often female (97.2 vs. 71.8%), from non-rural areas (93.9 vs. 89.9%), and resided in long-term care (10.9 vs. 3.3%). They had more comorbidities including dementia, falls, and fractures. Following their new prescription, denosumab users had more frequent testing of serum calcium. Duration of continuous use of denosumab was longer than bisphosphonates, and more bisphosphonate users had evidence of treatment discontinuation (56.7 bisphosphonate vs. 33.8% denosumab users discontinued therapy at 365 days). Compared with RCT participants, a higher proportion of "real-world" bisphosphonate and denosumab users had comorbidities including advanced kidney disease. CONCLUSION The clinical characteristics and monitoring of new users of bisphosphonates and denosumab generally align with practice guidelines, product monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.
-
7.
Bone Health in Childhood Chronic Disease.
Weber, DR
Endocrinology and metabolism clinics of North America. 2020;(4):637-650
-
-
Free full text
-
Abstract
Many children with chronic disease are now surviving into adulthood. As a result, there is a growing interest in optimizing bone health early in the disease course with the dual goals of improving quality of life during childhood and reducing life-long fracture risk. Risk factors for impaired bone health in these children include immobility, nutritional deficiency, exposure to bone toxic therapies, hormonal deficiencies affecting growth and pubertal development, and chronic inflammation. This review focuses on the chronic diseases of childhood most commonly associated with impaired bone health. Recent research findings and clinical practice recommendations, when available, for specific disorders are summarized.
-
8.
Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children.
Galindo-Zavala, R, Bou-Torrent, R, Magallares-López, B, Mir-Perelló, C, Palmou-Fontana, N, Sevilla-Pérez, B, Medrano-San Ildefonso, M, González-Fernández, MI, Román-Pascual, A, Alcañiz-Rodríguez, P, et al
Pediatric rheumatology online journal. 2020;(1):20
Abstract
BACKGROUND Osteoporosis incidence in children is increasing due to the increased survival rate of patients suffering from chronic diseases and the increased use of drugs that can damage bones. Recent changes made to the definition of childhood osteoporosis, along with the lack of guidelines or national consensuses regarding its diagnosis and treatment, have resulted in a wide variability in the approaches used to treat this disease. For these reasons, the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology has sounded the need for developing guidelines to standardize clinical practice with regard to this pathology. METHODS An expert panel comprised of 6 pediatricians and 5 rheumatologists carried out a qualitative literature review and provided recommendations based on evidence, when that was available, or on their own experience. The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system. A Delphi survey was conducted for those recommendations with an evidence level of IV or V. This survey was sent to all members of the SERPE. All recommendations that had a level of agreement higher or equal to 70% were included. RESULTS Fifty-one recommendations, categorized into eight sections, were obtained. Twenty-four of them presented an evidence level 4 or 5, and therefore a Delphi survey was conducted. This was submitted electronically and received a response rate of 40%. All recommendations submitted to the Delphi round obtained a level of agreement of 70% or higher and were therefore accepted. CONCLUSION In summary, we present herein guidelines for the prevention, diagnosis and treatment of secondary childhood osteoporosis based on the available evidence and expert clinical experience. We believe it can serve as a useful tool that will contribute to the standardization of clinical practice for this pathology. Prophylactic measures, early diagnosis and a proper therapeutic approach are essential to improving bone health, not only in children and adolescents, but also in the adults they will become in the future.
-
9.
Association of Bisphosphonate Therapy With Incident of Lower Extremity Fractures in Persons With Spinal Cord Injuries or Disorders.
Carbone, LD, Gonzalez, B, Miskevics, S, Ray, C, Etingen, B, Guihan, M, Craven, BC, George, V, Weaver, FM
Archives of physical medicine and rehabilitation. 2020;(4):633-641
Abstract
OBJECTIVE To investigate the association between prescriptions for bisphosphonates; calcium and vitamin D supplements; and receipt of dual-energy x-ray absorptiometry (DXA) screening, and incident fracture risk in men and women with a spinal cord injury (SCI) or disorder (SCID). DESIGN Propensity-matched case-control analyses. SETTING United States Veterans Affairs (VA) facilities. PARTICIPANTS A total of 7989 men and 849 women with an SCID included in VA administrative databases between October 1, 2005 and October 1, 2015 were identified (N=8838). Cases included 267 men and 59 women with a bisphosphonate prescription propensity matched with up to 4 controls. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Incident lower extremity fractures. RESULTS There was no significant association between prescriptions for bisphosphonates and incident lower extremity fractures in men (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.62-1.77) or women (OR, 1.02; 95% CI, 0.28-3.75). In men, similar null associations were seen among those who were adherent to bisphosphonate therapy (OR, 1.25; 95% CI, 0.73-2.16), were concomitant users of vitamin D and calcium and a bisphosphonate (OR, 1.05; 95% CI, 0.57-1.96), had more than 1 fracture on different dates during the study period (OR, 0.13; 95% CI, 0.02-1.16) and in those who had undergone DXA testing prior to the date of the bisphosphonate prescription and incident fracture (OR, 1.26; 95% CI, 0.69-2.32). CONCLUSIONS In men with a traumatic SCI and women with a traumatic SCID, bisphosphonate therapies for osteoporosis do not appear to significantly affect fracture risk. Adequately powered randomized controlled trials are needed to definitively demonstrate efficacy of bisphosphonates for fracture prevention in this population. There is a compelling need to identify new medications to prevent fractures in this high-risk population.
-
10.
Minodronate in the treatment of osteoporosis: A systematic review and meta-analysis.
Liu, Q, Chen, D, Ye, Z, Jin, Z, Ma, T, Huang, X
Medicine. 2020;(40):e22542
-
-
Free full text
-
Abstract
BACKGROUND The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).