In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
Objective: To study the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to determine the risk factors associated with the occurrence of this pathology. Method: An observational retrospective ...Objective: To study the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to determine the risk factors associated with the occurrence of this pathology. Method: An observational retrospective study was conducted in the Department of Oncology, Rheumatology, and Maxillofacial Surgery of Ibn Rochd University Hospital, Casablanca. The study utilized complete medical records from 2014 to 2022 and included consultations of patients receiving bisphosphonates (BPs) in July and September 2022. Statistical analysis was performed using SPSS version 16.0. Results: Our study population comprised 104 patients, of whom 91% were women and 49% were over 65 years old. Seventy-two percent of patients had a general pathology. Among them, 64 patients were treated with zoledronate, 43 with alendronate, and the remainder with risedronate, ibandronate, and pamidronate. The most common indications for treatment were bone metastasis following breast cancer (29.8%) and osteoporotic fractures (19.2%). Sixty-seven patients received intravenous (IV) treatment;only 10.5% exhibited good oral health. Fifty percent of patients underwent dental treatment, primarily tooth extractions. Osteonecrosis of the jaw (ONJ) was diagnosed in 1.9% of patients, predominantly in stages 1 and 2. Conclusion: Second and third-generation bisphosphonates are more strongly associated with the development of ONJ. Risk factors include monthly IV administration, poor oral health, comorbidities such as diabetes, medications like corticosteroids, invasive dental procedures, and not only oncological conditions but also rare indications such as bone algodystrophy. Nevertheless, our observed prevalence of 1.9% aligns with international rates ranging from 0.8% to 12%. However, most of the studies that have been carried out have been retrospective studies with insufficient numbers of patients. Further prospective epidemiological studies based on standardized protocols with rigorous and appropriate follow-up over several years are essential to determine the exact prevalence of ONJ.展开更多
BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatment...BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.展开更多
Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot(CF) presents with a red and swollen foot in co-ntrast to the painless deformed one of chronic CF. En-hanced...Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot(CF) presents with a red and swollen foot in co-ntrast to the painless deformed one of chronic CF. En-hanced osteoclastogenesis plays a central role in the pathogenesis of acute CF. Many studies have shown elevated levels of bone turnover markers in patients with acute CF confirming it. These findings have led cl-inicians to use anti-resorptive agents [bisphosphonates(BP), calcitonin, and denosumab] along with immobi-lization and offloading in acute CF patients. The ma-ximum evidence among all anti-resorptive agents is available for BPs, although its quality is low. Pamidronate has been shown to reduce the markers of activity of CF like raised skin temperature, pain, edema, and bone turnover markers in the majority of studies. Intravenous BPs are known to cause acute phase reactions leading to flu-like illness following their first infusion, which can be ameliorated by oral acetaminophen. Alendronate is the only oral BP used in these patients. It needs to be taken on an empty stomach with a full glass of water to avoid esophagitis. The side-effects and contraindications to BPs should be kept in mind while treating acute CF patients with them.展开更多
Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antian...Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.展开更多
Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytolo...Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.展开更多
AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital i...AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital in Beirut city,and its affiliated primary health care center.Data were collected through a new self-administered questionnaire distributed via a delegated secretary to physicians expected to regularly prescribe BPs(n = 215).It assessed participants' knowledge,fear and experience regarding BPsreported complications.RESULTS One hundred and fifty-seven physicians fulfilled the questionnaire(response rate: 73.0%): 77.7% and 75.2% considered that gastrointestinal intolerance and osteonecrosis of the jaw are linked to BPs,respectively.Conversely,the least recognised complications are ocular inflammation(7.6%) and severe musculoskeletal pain(37.6%).The association of BPs with oesophageal cancer,atrial fibrillation and hepatotoxicity was reported by 11.5%,13.4% and 24.8% of respondents,respectively.The multivariate analysis showed a significant association between level of knowledge and physicians' department affiliation(P-value = 0.043),their gender(P-value = 0.044),whether or not they prescribe a BP(P-value = 0.012),and the number of BP prescriptions delivered monthly(P-value = 0.012).Physicians are mainly concerned about osteonecrosis of the jaw and nephrotoxicity when prescribing a BP.Yet,the complications commonly met in their practice are gastrointestinal intolerance(44.6%) and acute phase reactions(26.7%).CONCLUSION This study revealed the presence of a deficient knowledge regarding BPs-related adverse events among our physicians.Professional training proposals are needed to increase their knowledge and improve their practices.Pharmaceutical industries should reconsider the instructions they provide to physicians regarding the complications of medications they promote.Moreover,they must actively collaborate with education providers and institutions in educational interventions.展开更多
Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old...Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old Caucasian female G2P2, with history of transient osteoporosis of both ankles and C-Section during the last pregnancy in 2011, presented progressively severe bilateral hip pain with onset already in the 12th gestational week. Imaging of the pelvis and bilateral hips with MRI obtained 6 days after the C-Section demonstrated bilateral bone-marrow edema of the hips. The patient was treated with a monthly single dose of 150 mg ibandronate acid per os, for 3 months and physiotherapy. Repeated MRI performed 5 months postpartum revealed a complete remission of the disease. In contrast to the first onset of transient osteoporosis during the first pregnancy, which was only treated conservatively without bisphosphonates, the remission of the disease and patient’s recovery with oral ibandronate therapy showed to be 4 months shorter. This case is unique in literature for both describing the onset of this rare disease twice in the same patient as well as its oral therapeutic approach.展开更多
There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to sear...There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite(HA), this study used three forms of ceramic materials,two of which are bone-stimulating materials, to assess the suitability of new active substances with antiresorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA(a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction(MINE) device(a polymer inert skeleton), respectively, were used. The affinity of risedronate(a standard compound) and sixteen aminomethylenebisphosphonates(new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorptionedesorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.展开更多
A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the a...A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.展开更多
Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of ...Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of “drug holidays” for bisphosphonates need optimization in order to minimize long-term exposure. Drug holidays may prevent potential adverse events while still maintaining some degree of antifracture efficacy via residual antiresorptive activity by retained bisphosphonates. Patients receiving bisphosphonates, who are at low-moderate risk of fracture, are potential candidates for a drug holiday. However, for high-risk patients or patients with previous history of fragility fractures, the benefits of continuing bisphosphonate therapy considerably out-weigh their potential harm. Evidence-based guidelines regarding starting and stopping a drug holiday are not available;therefore, it is appropriate to monitor patients on a drug holiday to assess a declining antiresorptive effect. In case of a significant rise in bone turnover markers or significant decrease in bone mineral density, it may be time to restart therapy.展开更多
Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione ...Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione (TZD) therapy with rosiglitazone and pioglitazone is associated with an increased risk of fractures and decreased bone mineral density (BMD). To our knowledge, no data are available to evaluate bisphosphonate therapy in thiazolidinedione-treated patients. The aim of this study was to investigate the benefit of bisphosphonates to improve changes in BMD in subjects with DM associated with TZDs. Methods: In a cross-sectional observational study using a retrospective review of electronic medical records, the changes in BMD in subjects with type 2 DM. The study subjects were divided into four groups. First group with DM receiving both TZDs and BPs;second group neither;third group receiving only TZDs and the fourth only BPs. The comparison of annual percent changes in BMD between the groups were carried out. Results: Decreased BMD noted in subjects with DM on TZDs. Bisphosphonates improved BMD in subjects with DM on TZDs. BMD improved in subjects with DM in those not receiving TZDs also. Conclusion: We conclude that concomitant treatment with bisphosphonates improves BMD in subjects with diabetes and on TZDs.展开更多
目的系统评价使用双膦酸盐药物(bisphosphonates,BPs)患者种植体早期失败率及种植术后药物相关性颌骨坏死(medication-related osteonecrosis of the jaw,MRONJ)发生率,为临床评估相关风险提供依据。方法计算机检索Cochrane Library、Wi...目的系统评价使用双膦酸盐药物(bisphosphonates,BPs)患者种植体早期失败率及种植术后药物相关性颌骨坏死(medication-related osteonecrosis of the jaw,MRONJ)发生率,为临床评估相关风险提供依据。方法计算机检索Cochrane Library、Wiley Online Library、PubMed、中国知网、万方数据知识服务平台,收集纳入各数据库建库至2022年5月发表的关于使用BPs患者种植体早期失败或种植术后发生MRONJ的临床研究。采用Stata 15.0软件对种植体早期失败率进行单组率Meta分析。结果共纳入13篇文献,其中口服BPs患者植入1182颗种植体,静脉注射BPs患者植入79颗,共计1261颗种植体。口服BPs患者合并种植体早期失败率为1.7%(95%CI:0.3%~3.9%),MRONJ发生率为0。静脉注射BPs患者种植体早期失败率为0,MRONJ发生率为5.6%。结论口服BPs患者种植体早期失败率及术后MRONJ发生率低,与健康人群基本相当。静脉使用BPs患者种植术后发生MRONJ风险较高,临床适应证选择应慎重。展开更多
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
文摘Objective: To study the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to determine the risk factors associated with the occurrence of this pathology. Method: An observational retrospective study was conducted in the Department of Oncology, Rheumatology, and Maxillofacial Surgery of Ibn Rochd University Hospital, Casablanca. The study utilized complete medical records from 2014 to 2022 and included consultations of patients receiving bisphosphonates (BPs) in July and September 2022. Statistical analysis was performed using SPSS version 16.0. Results: Our study population comprised 104 patients, of whom 91% were women and 49% were over 65 years old. Seventy-two percent of patients had a general pathology. Among them, 64 patients were treated with zoledronate, 43 with alendronate, and the remainder with risedronate, ibandronate, and pamidronate. The most common indications for treatment were bone metastasis following breast cancer (29.8%) and osteoporotic fractures (19.2%). Sixty-seven patients received intravenous (IV) treatment;only 10.5% exhibited good oral health. Fifty percent of patients underwent dental treatment, primarily tooth extractions. Osteonecrosis of the jaw (ONJ) was diagnosed in 1.9% of patients, predominantly in stages 1 and 2. Conclusion: Second and third-generation bisphosphonates are more strongly associated with the development of ONJ. Risk factors include monthly IV administration, poor oral health, comorbidities such as diabetes, medications like corticosteroids, invasive dental procedures, and not only oncological conditions but also rare indications such as bone algodystrophy. Nevertheless, our observed prevalence of 1.9% aligns with international rates ranging from 0.8% to 12%. However, most of the studies that have been carried out have been retrospective studies with insufficient numbers of patients. Further prospective epidemiological studies based on standardized protocols with rigorous and appropriate follow-up over several years are essential to determine the exact prevalence of ONJ.
文摘BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.
文摘Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot(CF) presents with a red and swollen foot in co-ntrast to the painless deformed one of chronic CF. En-hanced osteoclastogenesis plays a central role in the pathogenesis of acute CF. Many studies have shown elevated levels of bone turnover markers in patients with acute CF confirming it. These findings have led cl-inicians to use anti-resorptive agents [bisphosphonates(BP), calcitonin, and denosumab] along with immobi-lization and offloading in acute CF patients. The ma-ximum evidence among all anti-resorptive agents is available for BPs, although its quality is low. Pamidronate has been shown to reduce the markers of activity of CF like raised skin temperature, pain, edema, and bone turnover markers in the majority of studies. Intravenous BPs are known to cause acute phase reactions leading to flu-like illness following their first infusion, which can be ameliorated by oral acetaminophen. Alendronate is the only oral BP used in these patients. It needs to be taken on an empty stomach with a full glass of water to avoid esophagitis. The side-effects and contraindications to BPs should be kept in mind while treating acute CF patients with them.
文摘Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.
文摘Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.
文摘AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital in Beirut city,and its affiliated primary health care center.Data were collected through a new self-administered questionnaire distributed via a delegated secretary to physicians expected to regularly prescribe BPs(n = 215).It assessed participants' knowledge,fear and experience regarding BPsreported complications.RESULTS One hundred and fifty-seven physicians fulfilled the questionnaire(response rate: 73.0%): 77.7% and 75.2% considered that gastrointestinal intolerance and osteonecrosis of the jaw are linked to BPs,respectively.Conversely,the least recognised complications are ocular inflammation(7.6%) and severe musculoskeletal pain(37.6%).The association of BPs with oesophageal cancer,atrial fibrillation and hepatotoxicity was reported by 11.5%,13.4% and 24.8% of respondents,respectively.The multivariate analysis showed a significant association between level of knowledge and physicians' department affiliation(P-value = 0.043),their gender(P-value = 0.044),whether or not they prescribe a BP(P-value = 0.012),and the number of BP prescriptions delivered monthly(P-value = 0.012).Physicians are mainly concerned about osteonecrosis of the jaw and nephrotoxicity when prescribing a BP.Yet,the complications commonly met in their practice are gastrointestinal intolerance(44.6%) and acute phase reactions(26.7%).CONCLUSION This study revealed the presence of a deficient knowledge regarding BPs-related adverse events among our physicians.Professional training proposals are needed to increase their knowledge and improve their practices.Pharmaceutical industries should reconsider the instructions they provide to physicians regarding the complications of medications they promote.Moreover,they must actively collaborate with education providers and institutions in educational interventions.
文摘Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
文摘Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old Caucasian female G2P2, with history of transient osteoporosis of both ankles and C-Section during the last pregnancy in 2011, presented progressively severe bilateral hip pain with onset already in the 12th gestational week. Imaging of the pelvis and bilateral hips with MRI obtained 6 days after the C-Section demonstrated bilateral bone-marrow edema of the hips. The patient was treated with a monthly single dose of 150 mg ibandronate acid per os, for 3 months and physiotherapy. Repeated MRI performed 5 months postpartum revealed a complete remission of the disease. In contrast to the first onset of transient osteoporosis during the first pregnancy, which was only treated conservatively without bisphosphonates, the remission of the disease and patient’s recovery with oral ibandronate therapy showed to be 4 months shorter. This case is unique in literature for both describing the onset of this rare disease twice in the same patient as well as its oral therapeutic approach.
基金supported by the Ministry of Science and Higher Education grants and subsidy of the Ministry of Science and Higher Education。
文摘There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite(HA), this study used three forms of ceramic materials,two of which are bone-stimulating materials, to assess the suitability of new active substances with antiresorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA(a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction(MINE) device(a polymer inert skeleton), respectively, were used. The affinity of risedronate(a standard compound) and sixteen aminomethylenebisphosphonates(new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorptionedesorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.
文摘A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.
文摘Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of “drug holidays” for bisphosphonates need optimization in order to minimize long-term exposure. Drug holidays may prevent potential adverse events while still maintaining some degree of antifracture efficacy via residual antiresorptive activity by retained bisphosphonates. Patients receiving bisphosphonates, who are at low-moderate risk of fracture, are potential candidates for a drug holiday. However, for high-risk patients or patients with previous history of fragility fractures, the benefits of continuing bisphosphonate therapy considerably out-weigh their potential harm. Evidence-based guidelines regarding starting and stopping a drug holiday are not available;therefore, it is appropriate to monitor patients on a drug holiday to assess a declining antiresorptive effect. In case of a significant rise in bone turnover markers or significant decrease in bone mineral density, it may be time to restart therapy.
文摘Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione (TZD) therapy with rosiglitazone and pioglitazone is associated with an increased risk of fractures and decreased bone mineral density (BMD). To our knowledge, no data are available to evaluate bisphosphonate therapy in thiazolidinedione-treated patients. The aim of this study was to investigate the benefit of bisphosphonates to improve changes in BMD in subjects with DM associated with TZDs. Methods: In a cross-sectional observational study using a retrospective review of electronic medical records, the changes in BMD in subjects with type 2 DM. The study subjects were divided into four groups. First group with DM receiving both TZDs and BPs;second group neither;third group receiving only TZDs and the fourth only BPs. The comparison of annual percent changes in BMD between the groups were carried out. Results: Decreased BMD noted in subjects with DM on TZDs. Bisphosphonates improved BMD in subjects with DM on TZDs. BMD improved in subjects with DM in those not receiving TZDs also. Conclusion: We conclude that concomitant treatment with bisphosphonates improves BMD in subjects with diabetes and on TZDs.
文摘目的系统评价使用双膦酸盐药物(bisphosphonates,BPs)患者种植体早期失败率及种植术后药物相关性颌骨坏死(medication-related osteonecrosis of the jaw,MRONJ)发生率,为临床评估相关风险提供依据。方法计算机检索Cochrane Library、Wiley Online Library、PubMed、中国知网、万方数据知识服务平台,收集纳入各数据库建库至2022年5月发表的关于使用BPs患者种植体早期失败或种植术后发生MRONJ的临床研究。采用Stata 15.0软件对种植体早期失败率进行单组率Meta分析。结果共纳入13篇文献,其中口服BPs患者植入1182颗种植体,静脉注射BPs患者植入79颗,共计1261颗种植体。口服BPs患者合并种植体早期失败率为1.7%(95%CI:0.3%~3.9%),MRONJ发生率为0。静脉注射BPs患者种植体早期失败率为0,MRONJ发生率为5.6%。结论口服BPs患者种植体早期失败率及术后MRONJ发生率低,与健康人群基本相当。静脉使用BPs患者种植术后发生MRONJ风险较高,临床适应证选择应慎重。
