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 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
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
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
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
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
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
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
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
Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bac...Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. Denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.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.
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
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
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
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
In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, oractinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as p...In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, oractinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as protecting group to avoid the breakage of amide by acid hydrolysis orimcomplete reaction in silylation-dealkylation using bromotrimethylsilane.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
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 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.
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.
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.
基金supported by NIH grants CA172894, CA180277, DE020891New York University Research Funds
文摘Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. Denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.
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.
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.
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In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, oractinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as protecting group to avoid the breakage of amide by acid hydrolysis orimcomplete reaction in silylation-dealkylation using bromotrimethylsilane.
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.
