Simple, efficient and convenient synthesis of aminomethylene bisphsophonic acid derivatives in one-pot reaction using aldehydes, hydroxylamine hydrochloride, phosphours trichloride and water as starting materials in t...Simple, efficient and convenient synthesis of aminomethylene bisphsophonic acid derivatives in one-pot reaction using aldehydes, hydroxylamine hydrochloride, phosphours trichloride and water as starting materials in the presence of pyridine was described.展开更多
BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Hepatic osteodystrophy(HO)is a common and frequently untreated complica-tion,manifested as osteoporosis or osteopenia,encountered in the evolution of chronic liver diseases(CLD).In addition to patients with chronic ch...Hepatic osteodystrophy(HO)is a common and frequently untreated complica-tion,manifested as osteoporosis or osteopenia,encountered in the evolution of chronic liver diseases(CLD).In addition to patients with chronic cholestasis and cirrhosis,patients with CLD from other etiologies may be affected.Several studies have reported an increased prevalence of osteoporosis/osteopenia in patients with CLD.The pathogenesis varies according to etiology and is multifactorial,involving genetic factors,vitamin deficiencies,proinflammatory cytokines,hypo-gonadism,hyperbilirubinemia,antiviral therapy,corticosteroids,and lifestyle fa-ctors.The approach to management should include individualized assessment for fracture risk factors and bone mineral density.Prevention of osteoporosis in CLD relies on the mitigation of risk factors,treatment of underlying hypogonadism,and encouraging a healthy diet and weight-bearing exercise.Treatment trials specific to HO are small,and the primary medical intervention for the treatment of osteoporosis in CLD remains bisphosphonates although the benefit in fracture reduction has not consistently been shown.Further research is necessary to better define the management and specific treatment of HO for the prevention of fragility fractures and to improve the quality of life.This article provides an updated review of HO covering all these aspects.展开更多
BACKGROUND Aneurysmal bone cysts(ABCs)are usually treated with curettage or various minimally invasive percutaneous procedures.Patient refractory to these treatments,as well as those with locally advanced or unresecta...BACKGROUND Aneurysmal bone cysts(ABCs)are usually treated with curettage or various minimally invasive percutaneous procedures.Patient refractory to these treatments,as well as those with locally advanced or unresectable tumors,present a challenge for orthopedic surgeons and require new treatment approaches.Antiresorptive drugs inhibit osteoclastic resorption and increase intralesional osteogenesis.Denosumab induces tumor ossification,but this effect may disappear after drug withdrawal due to limited impact on neoplastic cells.Bisphosphonates(BPs)may induce apoptosis of tumor cells and allow for long-term local control.We hypothesized that after denosumab treatment,BPs would better accumulate in the tumor and exert an irreversible antitumor effect.AIM To test the hypothesis that the sequential use of BPs after denosumab induction improves treatment outcomes in surgically unsalvageable ABCs.METHODS Using data from five electronic databases(Scopus,MEDLINE,EMBASE,PubMed,Web of Science),we aimed to identify all patients who received denosumab therapy(DT)for unresectable ABCs.Among published case reports and case series,we identified patients who discontinued denosumab for various reasons and divided them into two groups:Group 1 included 31 patients without further anti-resorptive therapy and Group 2 included 12 patients who received BPs in the context of rebound hypercalcemia.Local control rates in both groups were analyzed.RESULTS As of December 2024,43 patients have been reported in the literature who received DT for locally advanced/unresectable ABCs.There were 27 males and 16 females with a mean age of 15.8 years.At a median follow-up time of 15.5 months,there were 10 confirmed and two pathologically unconfirmed relapses after denosumab discontinuation.All 10 relapses occurred in patients in Group 1 at a median time of 13.5 months.Among patients in Group 2,with a median follow-up time of 12.5 months after completion of therapy,no local relapses were observed.The difference between local recurrence rates(32%vs 0%)is statistically significant(P value=0.02).Kaplan-Meier estimates show the same trend with marginal statistical significance(P value=0.085).Here we put forward a novel treatment algorithm.CONCLUSION BPs used in post-denosumab ossifying ABCs appear to improve treatment outcomes,presumably by targeting residual tumor cells.Prospective clinical studies are warranted to validate this promising two-stage conceptual strategy in difficult-to-treat ABC.展开更多
Background: Bisphosphonates are compounds similar to inorganic pyrophosphates, with anti-angiogenic, anti-inflammatory, anti-bone resorption, and antitumor effects. They are used to prevent bone metastases in cancer a...Background: Bisphosphonates are compounds similar to inorganic pyrophosphates, with anti-angiogenic, anti-inflammatory, anti-bone resorption, and antitumor effects. They are used to prevent bone metastases in cancer and treat osteoporosis. However, a major side effect is osteonecrosis of the jaw (ONJ), first reported in 2003, which is the exposure of necrotic bone in the mouth, often accompanied by infection. Prevention and treatment of ONJ remain challenging due to a lack of reliable epidemiological data on its incidence and risk factors. The aim of our work is to estimate the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to analyze its correlations with different risk factors reported in the literature. Methods: A retrospective observational study was conducted in the Oncology, Rheumatology and Maxillofacial Surgery Department of the Mohamed VI University Hospital;Marrakech, based on complete medical records during the period 2017 to 2022, as well as consultations of patients under bisphosphonates in these departments during July and August 2022. Statistical analysis was performed using IBM SPSS version 16.0. Results: Of the 107 patients included in this study, 60.7% were women, and 56.1% were between 40 and 65 years old. 100% of the patients suffered from a general pathology. Regarding treatment with BP, 103 patients were treated with Zoledronate, 4 with Risedronate, and 5 with Ibandronate. 103 patients received this treatment intravenously, while 4 patients received it orally. Regarding Oral health, only 12.1% of patients reported a poor oral health. 99.1% of patients were informed of the need for oral preparation prior to BP treatment, but only 71.02% received dental treatment, mainly tooth extraction. None of the patients were diagnosed with BRONJ. Conclusions: While the global incidence of ONJ ranges from 0.8% to 12%, our finding is zero. Most previous studies are retrospective with limited patient numbers like our study. To accurately assess the prevalence of ONJ, further prospective epidemiological studies with standardized protocols and thorough follow-up over several years are essential.展开更多
BACKGROUND Chronic recurrent multifocal osteomyelitis(CRMO)is a rare autoinflammatory bone disorder primarily affecting children and adolescents.Spinal involvement in CRMO is common and can lead to significant clinica...BACKGROUND Chronic recurrent multifocal osteomyelitis(CRMO)is a rare autoinflammatory bone disorder primarily affecting children and adolescents.Spinal involvement in CRMO is common and can lead to significant clinical features and complications,including severe chronic back pain and spinal deformities with possible spinal cord compression.AIM To summarize the information about vertebral involvement in CRMO patients,including the clinical features,diagnostic approaches,and treatment outcomes.METHODS Sixty-three manuscripts(2005-2025)were found in PubMed,including case reports,retrospective cohort studies,randomized controlled trials,and imaging studies.The focus was on spinal involvement features,diagnostic imaging,treatment strategies,and long-term outcomes in pediatric CRMO patients.RESULTS Spinal involvement in CRMO ranges from 28%to 81%among patients with CRMO.Patients typically present with localized back pain,back stiffness,and,in more severe cases,spinal deformities such as kyphosis or scoliosis.Multifocal lesions are frequently observed,with the thoracic spine being the most commonly affected area.Whole-body magnetic resonance imaging(WBMRI)has emerged as the gold standard for effectively revealing multifocal bone lesions and spinal involvement.However,a bone biopsy is often needed to rule out infection or malignancy.Bisphosphonate treatment showed a high response rate(90.9%),while tumor necrosis factor-alpha(TNF-α)inhibitors were less effective(66.7%).Long-term follow-up is crucial,as relapses and progression of spinal deformities can occur even with treatment.CONCLUSION Spinal involvement in CRMO often leads to chronic pain,vertebral deformities,and rare spinal deformities.Early diagnosis using WBMRI,combined with treatment with bisphosphonates and TNF-αinhibitors,could improve outcomes.展开更多
Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical feat...Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.展开更多
Primary biliary cholangitis(PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to signifi...Primary biliary cholangitis(PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from Pub Med, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies.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
Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cel...Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand(RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.展开更多
A number of effective therapies for the treatment of osteoporosis have become available in recent years. However, uncertainty exists regarding their long-term use and effectiveness. Bisphosphonate treatment, unlike ho...A number of effective therapies for the treatment of osteoporosis have become available in recent years. However, uncertainty exists regarding their long-term use and effectiveness. Bisphosphonate treatment, unlike hormone replacement, denosumab or teriparatide, is associated with benefits extended even after treatment discontinuation. The extended benefits are most apparent for alendronate （ALN） and zoledronate （ZOL）. A drug holiday might be considered in patients compliant with treatment, and who have had a response fractures the decision to consider a drug holiday should treatment. at low-moderate risk and who have been fully to treatment. In patients at low-moderate risk of be balanced also with the safety profile of each展开更多
To investigate the efficiency of clodronate modifying HA bioceramics,and to evaluate the effect of clodronate modifying HA bioceramics on the cells in vitro,clodronate modified the porous HA bioceramics for bone scaff...To investigate the efficiency of clodronate modifying HA bioceramics,and to evaluate the effect of clodronate modifying HA bioceramics on the cells in vitro,clodronate modified the porous HA bioceramics for bone scaffold by chelation .The outermost layer of the specimens was analyzd by XPS and FI-IR ,The depth profile was investigated by the argon-ion sputtering method.The cell culture test was conducted using MC3T3-E1 osteoblastic cells,The cells were inoculated and cultured on the scaffolds.Morphological observation of the cells,MTT test and ALP activity test evaluated the cell attachment ,proliferation and activity on the scaffolds.The cell culture test in cell quantity and morphology indicated active proliferation of the cells on the scaffolds.The ALP activity of the cells cultured for 3d and 7d on clodronate-HA bioceramics was slightly higher than that on HA bioceramics ,but the difference was not signifcant,This result indicated that clodronate-HA bioeramics had favorable cytocompatibility to be used as bone scaffold with potential ability to improve asteogensis.展开更多
BACKGROUND Simultaneous bilateral femoral neck fractures are relatively rare injuries.They are usually associated with underlying metabolic bone disorders or systemic diseases.Long-term use of narcotics and bisphospho...BACKGROUND Simultaneous bilateral femoral neck fractures are relatively rare injuries.They are usually associated with underlying metabolic bone disorders or systemic diseases.Long-term use of narcotics and bisphosphonates can also result in similar fracture patterns;however,association of this fracture type with longterm use of antiepileptic drugs is not very common.Only one such case has been reported in the literature.This article describes the second.CASE REPORT We report a case of simultaneous displaced bilateral femoral neck fractures in a 50-year-old epileptic patient,who had taken phenytoin for the past 3 years.The fractures were a result of low-velocity injury following a fall from the bed.The fractures were managed with a bilateral hemi-replacement arthroplasty.Oral bisphosphonates were given to improve the bone quality in the post-operative period.The patient had a good post-operative outcome,that was sustained throughout the entire follow-up period of 1 year.CONCLUSION Antiepileptic drugs should be supplemented with bisphosphonates and vitamin D to improve bone quality and prevent fractures in epileptic patients.展开更多
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
AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDL...AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDLINE,EMBASE,and the Cochrane Library to identify studies through January 2011.Search terms were "bisphosphonates" or trade names of the drugs,and "observational studies" or "cohort studies" or "case-control studies".Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed:(1) observational studies(casecontrol or cohort studies) on bisphosphonate use;(2) with at least 2 years of follow-up;and(3) reported data on the incidence of cancer diagnosis.The DerSimonian and Laird random effects model were used to calculate the pooled relative risk(RR) with 95% confidence interval(CI).Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis.Subgroup meta-analyses were conducted for the type of cancer(esophageal,gastric and colorectal cancers).Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up(mean 5 years;subgroup 3 years) were included.RESULTS:Of 740 screened articles,3 cohort studies and 3 case-control studies were included in the analyses.At first,4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer.More than 124 686 subjects participated in the 3 cohort studies.The mean follow-up time in all of the cohort studies combined was approximately 3.88 years.The 3 casecontrol studies reported 3070 esophageal cancer cases and 15 417 controls,2018 gastric cancer cases and 10 007 controls,and 11 574 colorectal cancer cases and 53 955 controls.The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls.The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer.Also no statistically significant association was found in a meta-analysis of long-term follow-up studies.There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis(RR 0.96,95% CI:0.65-1.42,I 2 = 52.8%,P = 0.076) and no statistically significant association with long-term follow-up(RR 1.74,95% CI:0.97-3.10,I 2 = 58.8%,P = 0.119).No negative association was found in the studies reporting the risk of gastric cancer(RR 0.89,95% CI:0.71-1.13,I 2 = 0.0%,P = 0.472).In case of colorectal cancer,there was no association between colorectal cancer and bisphosphonate use(RR 0.62,95% CI:0.30-1.29,I 2 = 88.0%,P = 0.004) and also in the analysis with long-term follow-up(RR 0.61,95% CI:0.28-1.35,I 2 = 84.6%,P = 0.011).CONCLUSION:Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk.However,this finding should be validated in randomized controlled trials with long-term follow-up.展开更多
Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb ...Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone.Whilst aiming to reduce the risk of fragility fractures,bisphosphonates have been associated with atypical insufficiency fractures,specifically in the femur.Atypical femoral fractures occur distal to the lesser trochanter,until the supracondylar flare.There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures,indicating that there is a distinct difference in the respective underlying pathophysiology.At the point of presentation of an atypical femoral fracture,bisphosphonate should be discontinued.This is due to the proposed inhibition of osteoclasts and apoptosis,resulting in impaired callus healing.Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity.Nutritional deficiencies should be investigated and appro-priately corrected,most notably dietary calcium and vitamin D.Currently there is no established treatment guidelines for either complete or incomplete fractures.There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes.Currently,the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation.Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex,with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share,and a reduced bending moment across the fracture site.The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates.However,it is important to appreciate that the anatomical location and patient factors may not always allow for this.Although causation between bisphosphonates and atypical fractures is yet to be demonstrated,there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates.As we encounter a growing comorbid elderly population,the prevalence of this fracture-type will likely increase.Therefore,it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.展开更多
Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival o...Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.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
Osteoporotic fracture with increase of aging population became an urgent orthopedic problem.Bisphosphonates were widely recommended as effective clinical treatment drugs.Combination of biodegradable Mg-based implants ...Osteoporotic fracture with increase of aging population became an urgent orthopedic problem.Bisphosphonates were widely recommended as effective clinical treatment drugs.Combination of biodegradable Mg-based implants and merits of bisphosphonates was suggested for osteoporotic fracture healing.Considering the mild and sustained drug release,a novel one-step electrodeposition synthesis of drug loaded coating was proposed in this study.In comparison to conventional soaking method,encapsulated zoledronate coating by one-step electrodeposition method could modulate drug release in first diffusion-controlled and later degradation-controlled manner.The in vitro cell response to zoledronate loaded coating showed enhanced proliferation and osteogenic differentiation of osteoblasts and no significant inhibition on osteoclasts,which could improve bone-forming and decrease bone resorption due to osteoporosis.展开更多
As a systemic metabolic disease caused by a variety of factors,osteoporosis is characterized by reduced bone mass,bone tissue microstructural degradation,and decreased bone mechanical properties,accompanied by bone fr...As a systemic metabolic disease caused by a variety of factors,osteoporosis is characterized by reduced bone mass,bone tissue microstructural degradation,and decreased bone mechanical properties,accompanied by bone fragility and fracture,which is a common risk of senile disease.In China,osteoporosis has become a common disease and has frequent morbidity,with the incidence trend on the rise.Bisphosphates have received much attention in this field as inhibitory bone resorption agents,and sodium olpadronate belongs to the third-generation bisphosphonates.This experiment investigated the synthetic process and pharmacological activity of sodium olpadronate.Using 3-(N,N-dimethylamino)-propionitrile as the starting material,the synthesis process was improved to reduce cost with a total yield of 49.7%,which was 24.0%higher than that reported in the literature.Pharmacodynamic experiments showed that sodium olpadronate could be used to treat osteoporosis.Moreover,toxicology experiments showed no obvious toxic side effects.Taken together,sodium olpadronate had very promising development prospects.展开更多
文摘Simple, efficient and convenient synthesis of aminomethylene bisphsophonic acid derivatives in one-pot reaction using aldehydes, hydroxylamine hydrochloride, phosphours trichloride and water as starting materials in the presence of pyridine was described.
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
文摘Hepatic osteodystrophy(HO)is a common and frequently untreated complica-tion,manifested as osteoporosis or osteopenia,encountered in the evolution of chronic liver diseases(CLD).In addition to patients with chronic cholestasis and cirrhosis,patients with CLD from other etiologies may be affected.Several studies have reported an increased prevalence of osteoporosis/osteopenia in patients with CLD.The pathogenesis varies according to etiology and is multifactorial,involving genetic factors,vitamin deficiencies,proinflammatory cytokines,hypo-gonadism,hyperbilirubinemia,antiviral therapy,corticosteroids,and lifestyle fa-ctors.The approach to management should include individualized assessment for fracture risk factors and bone mineral density.Prevention of osteoporosis in CLD relies on the mitigation of risk factors,treatment of underlying hypogonadism,and encouraging a healthy diet and weight-bearing exercise.Treatment trials specific to HO are small,and the primary medical intervention for the treatment of osteoporosis in CLD remains bisphosphonates although the benefit in fracture reduction has not consistently been shown.Further research is necessary to better define the management and specific treatment of HO for the prevention of fragility fractures and to improve the quality of life.This article provides an updated review of HO covering all these aspects.
文摘BACKGROUND Aneurysmal bone cysts(ABCs)are usually treated with curettage or various minimally invasive percutaneous procedures.Patient refractory to these treatments,as well as those with locally advanced or unresectable tumors,present a challenge for orthopedic surgeons and require new treatment approaches.Antiresorptive drugs inhibit osteoclastic resorption and increase intralesional osteogenesis.Denosumab induces tumor ossification,but this effect may disappear after drug withdrawal due to limited impact on neoplastic cells.Bisphosphonates(BPs)may induce apoptosis of tumor cells and allow for long-term local control.We hypothesized that after denosumab treatment,BPs would better accumulate in the tumor and exert an irreversible antitumor effect.AIM To test the hypothesis that the sequential use of BPs after denosumab induction improves treatment outcomes in surgically unsalvageable ABCs.METHODS Using data from five electronic databases(Scopus,MEDLINE,EMBASE,PubMed,Web of Science),we aimed to identify all patients who received denosumab therapy(DT)for unresectable ABCs.Among published case reports and case series,we identified patients who discontinued denosumab for various reasons and divided them into two groups:Group 1 included 31 patients without further anti-resorptive therapy and Group 2 included 12 patients who received BPs in the context of rebound hypercalcemia.Local control rates in both groups were analyzed.RESULTS As of December 2024,43 patients have been reported in the literature who received DT for locally advanced/unresectable ABCs.There were 27 males and 16 females with a mean age of 15.8 years.At a median follow-up time of 15.5 months,there were 10 confirmed and two pathologically unconfirmed relapses after denosumab discontinuation.All 10 relapses occurred in patients in Group 1 at a median time of 13.5 months.Among patients in Group 2,with a median follow-up time of 12.5 months after completion of therapy,no local relapses were observed.The difference between local recurrence rates(32%vs 0%)is statistically significant(P value=0.02).Kaplan-Meier estimates show the same trend with marginal statistical significance(P value=0.085).Here we put forward a novel treatment algorithm.CONCLUSION BPs used in post-denosumab ossifying ABCs appear to improve treatment outcomes,presumably by targeting residual tumor cells.Prospective clinical studies are warranted to validate this promising two-stage conceptual strategy in difficult-to-treat ABC.
文摘Background: Bisphosphonates are compounds similar to inorganic pyrophosphates, with anti-angiogenic, anti-inflammatory, anti-bone resorption, and antitumor effects. They are used to prevent bone metastases in cancer and treat osteoporosis. However, a major side effect is osteonecrosis of the jaw (ONJ), first reported in 2003, which is the exposure of necrotic bone in the mouth, often accompanied by infection. Prevention and treatment of ONJ remain challenging due to a lack of reliable epidemiological data on its incidence and risk factors. The aim of our work is to estimate the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to analyze its correlations with different risk factors reported in the literature. Methods: A retrospective observational study was conducted in the Oncology, Rheumatology and Maxillofacial Surgery Department of the Mohamed VI University Hospital;Marrakech, based on complete medical records during the period 2017 to 2022, as well as consultations of patients under bisphosphonates in these departments during July and August 2022. Statistical analysis was performed using IBM SPSS version 16.0. Results: Of the 107 patients included in this study, 60.7% were women, and 56.1% were between 40 and 65 years old. 100% of the patients suffered from a general pathology. Regarding treatment with BP, 103 patients were treated with Zoledronate, 4 with Risedronate, and 5 with Ibandronate. 103 patients received this treatment intravenously, while 4 patients received it orally. Regarding Oral health, only 12.1% of patients reported a poor oral health. 99.1% of patients were informed of the need for oral preparation prior to BP treatment, but only 71.02% received dental treatment, mainly tooth extraction. None of the patients were diagnosed with BRONJ. Conclusions: While the global incidence of ONJ ranges from 0.8% to 12%, our finding is zero. Most previous studies are retrospective with limited patient numbers like our study. To accurately assess the prevalence of ONJ, further prospective epidemiological studies with standardized protocols and thorough follow-up over several years are essential.
文摘BACKGROUND Chronic recurrent multifocal osteomyelitis(CRMO)is a rare autoinflammatory bone disorder primarily affecting children and adolescents.Spinal involvement in CRMO is common and can lead to significant clinical features and complications,including severe chronic back pain and spinal deformities with possible spinal cord compression.AIM To summarize the information about vertebral involvement in CRMO patients,including the clinical features,diagnostic approaches,and treatment outcomes.METHODS Sixty-three manuscripts(2005-2025)were found in PubMed,including case reports,retrospective cohort studies,randomized controlled trials,and imaging studies.The focus was on spinal involvement features,diagnostic imaging,treatment strategies,and long-term outcomes in pediatric CRMO patients.RESULTS Spinal involvement in CRMO ranges from 28%to 81%among patients with CRMO.Patients typically present with localized back pain,back stiffness,and,in more severe cases,spinal deformities such as kyphosis or scoliosis.Multifocal lesions are frequently observed,with the thoracic spine being the most commonly affected area.Whole-body magnetic resonance imaging(WBMRI)has emerged as the gold standard for effectively revealing multifocal bone lesions and spinal involvement.However,a bone biopsy is often needed to rule out infection or malignancy.Bisphosphonate treatment showed a high response rate(90.9%),while tumor necrosis factor-alpha(TNF-α)inhibitors were less effective(66.7%).Long-term follow-up is crucial,as relapses and progression of spinal deformities can occur even with treatment.CONCLUSION Spinal involvement in CRMO often leads to chronic pain,vertebral deformities,and rare spinal deformities.Early diagnosis using WBMRI,combined with treatment with bisphosphonates and TNF-αinhibitors,could improve outcomes.
文摘Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.
基金Supported by NIH T32 training grant,No.4T32GM103702-04 to Trivedi HD
文摘Primary biliary cholangitis(PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from Pub Med, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies.
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Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand(RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.
文摘A number of effective therapies for the treatment of osteoporosis have become available in recent years. However, uncertainty exists regarding their long-term use and effectiveness. Bisphosphonate treatment, unlike hormone replacement, denosumab or teriparatide, is associated with benefits extended even after treatment discontinuation. The extended benefits are most apparent for alendronate （ALN） and zoledronate （ZOL）. A drug holiday might be considered in patients compliant with treatment, and who have had a response fractures the decision to consider a drug holiday should treatment. at low-moderate risk and who have been fully to treatment. In patients at low-moderate risk of be balanced also with the safety profile of each
文摘To investigate the efficiency of clodronate modifying HA bioceramics,and to evaluate the effect of clodronate modifying HA bioceramics on the cells in vitro,clodronate modified the porous HA bioceramics for bone scaffold by chelation .The outermost layer of the specimens was analyzd by XPS and FI-IR ,The depth profile was investigated by the argon-ion sputtering method.The cell culture test was conducted using MC3T3-E1 osteoblastic cells,The cells were inoculated and cultured on the scaffolds.Morphological observation of the cells,MTT test and ALP activity test evaluated the cell attachment ,proliferation and activity on the scaffolds.The cell culture test in cell quantity and morphology indicated active proliferation of the cells on the scaffolds.The ALP activity of the cells cultured for 3d and 7d on clodronate-HA bioceramics was slightly higher than that on HA bioceramics ,but the difference was not signifcant,This result indicated that clodronate-HA bioeramics had favorable cytocompatibility to be used as bone scaffold with potential ability to improve asteogensis.
文摘BACKGROUND Simultaneous bilateral femoral neck fractures are relatively rare injuries.They are usually associated with underlying metabolic bone disorders or systemic diseases.Long-term use of narcotics and bisphosphonates can also result in similar fracture patterns;however,association of this fracture type with longterm use of antiepileptic drugs is not very common.Only one such case has been reported in the literature.This article describes the second.CASE REPORT We report a case of simultaneous displaced bilateral femoral neck fractures in a 50-year-old epileptic patient,who had taken phenytoin for the past 3 years.The fractures were a result of low-velocity injury following a fall from the bed.The fractures were managed with a bilateral hemi-replacement arthroplasty.Oral bisphosphonates were given to improve the bone quality in the post-operative period.The patient had a good post-operative outcome,that was sustained throughout the entire follow-up period of 1 year.CONCLUSION Antiepileptic drugs should be supplemented with bisphosphonates and vitamin D to improve bone quality and prevent fractures in epileptic patients.
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.
基金Supported by The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,Science and Technology,No.2012-0003761
文摘AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDLINE,EMBASE,and the Cochrane Library to identify studies through January 2011.Search terms were "bisphosphonates" or trade names of the drugs,and "observational studies" or "cohort studies" or "case-control studies".Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed:(1) observational studies(casecontrol or cohort studies) on bisphosphonate use;(2) with at least 2 years of follow-up;and(3) reported data on the incidence of cancer diagnosis.The DerSimonian and Laird random effects model were used to calculate the pooled relative risk(RR) with 95% confidence interval(CI).Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis.Subgroup meta-analyses were conducted for the type of cancer(esophageal,gastric and colorectal cancers).Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up(mean 5 years;subgroup 3 years) were included.RESULTS:Of 740 screened articles,3 cohort studies and 3 case-control studies were included in the analyses.At first,4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer.More than 124 686 subjects participated in the 3 cohort studies.The mean follow-up time in all of the cohort studies combined was approximately 3.88 years.The 3 casecontrol studies reported 3070 esophageal cancer cases and 15 417 controls,2018 gastric cancer cases and 10 007 controls,and 11 574 colorectal cancer cases and 53 955 controls.The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls.The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer.Also no statistically significant association was found in a meta-analysis of long-term follow-up studies.There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis(RR 0.96,95% CI:0.65-1.42,I 2 = 52.8%,P = 0.076) and no statistically significant association with long-term follow-up(RR 1.74,95% CI:0.97-3.10,I 2 = 58.8%,P = 0.119).No negative association was found in the studies reporting the risk of gastric cancer(RR 0.89,95% CI:0.71-1.13,I 2 = 0.0%,P = 0.472).In case of colorectal cancer,there was no association between colorectal cancer and bisphosphonate use(RR 0.62,95% CI:0.30-1.29,I 2 = 88.0%,P = 0.004) and also in the analysis with long-term follow-up(RR 0.61,95% CI:0.28-1.35,I 2 = 84.6%,P = 0.011).CONCLUSION:Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk.However,this finding should be validated in randomized controlled trials with long-term follow-up.
文摘Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone.Whilst aiming to reduce the risk of fragility fractures,bisphosphonates have been associated with atypical insufficiency fractures,specifically in the femur.Atypical femoral fractures occur distal to the lesser trochanter,until the supracondylar flare.There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures,indicating that there is a distinct difference in the respective underlying pathophysiology.At the point of presentation of an atypical femoral fracture,bisphosphonate should be discontinued.This is due to the proposed inhibition of osteoclasts and apoptosis,resulting in impaired callus healing.Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity.Nutritional deficiencies should be investigated and appro-priately corrected,most notably dietary calcium and vitamin D.Currently there is no established treatment guidelines for either complete or incomplete fractures.There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes.Currently,the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation.Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex,with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share,and a reduced bending moment across the fracture site.The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates.However,it is important to appreciate that the anatomical location and patient factors may not always allow for this.Although causation between bisphosphonates and atypical fractures is yet to be demonstrated,there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates.As we encounter a growing comorbid elderly population,the prevalence of this fracture-type will likely increase.Therefore,it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.
基金financially supported by the National Natural Science Foundation of China (Nos. 31600811, 81573154, 81773432)the Application Fundamental Research Foundation of Sichuan Province Science and Technology Department, China (Nos. 2016JY0157, 2017JY0123)Scientific Research Foundation of the Health and Family Planning Commission of Sichuan Province, China (Nos. 17PJ556, 17PJ563)
文摘Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.
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.
基金National Natural Science Foundation of China(No.31500777)Research start-up funds of DGUT(No.GC300501-082)Scientific Research Foundation for Young Team of DGUT(No.TDQN2019005)。
文摘Osteoporotic fracture with increase of aging population became an urgent orthopedic problem.Bisphosphonates were widely recommended as effective clinical treatment drugs.Combination of biodegradable Mg-based implants and merits of bisphosphonates was suggested for osteoporotic fracture healing.Considering the mild and sustained drug release,a novel one-step electrodeposition synthesis of drug loaded coating was proposed in this study.In comparison to conventional soaking method,encapsulated zoledronate coating by one-step electrodeposition method could modulate drug release in first diffusion-controlled and later degradation-controlled manner.The in vitro cell response to zoledronate loaded coating showed enhanced proliferation and osteogenic differentiation of osteoblasts and no significant inhibition on osteoclasts,which could improve bone-forming and decrease bone resorption due to osteoporosis.
文摘As a systemic metabolic disease caused by a variety of factors,osteoporosis is characterized by reduced bone mass,bone tissue microstructural degradation,and decreased bone mechanical properties,accompanied by bone fragility and fracture,which is a common risk of senile disease.In China,osteoporosis has become a common disease and has frequent morbidity,with the incidence trend on the rise.Bisphosphates have received much attention in this field as inhibitory bone resorption agents,and sodium olpadronate belongs to the third-generation bisphosphonates.This experiment investigated the synthetic process and pharmacological activity of sodium olpadronate.Using 3-(N,N-dimethylamino)-propionitrile as the starting material,the synthesis process was improved to reduce cost with a total yield of 49.7%,which was 24.0%higher than that reported in the literature.Pharmacodynamic experiments showed that sodium olpadronate could be used to treat osteoporosis.Moreover,toxicology experiments showed no obvious toxic side effects.Taken together,sodium olpadronate had very promising development prospects.
