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
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
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
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
Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antian...Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.展开更多
Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytolo...Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.展开更多
AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital i...AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital in Beirut city,and its affiliated primary health care center.Data were collected through a new self-administered questionnaire distributed via a delegated secretary to physicians expected to regularly prescribe BPs(n = 215).It assessed participants' knowledge,fear and experience regarding BPsreported complications.RESULTS One hundred and fifty-seven physicians fulfilled the questionnaire(response rate: 73.0%): 77.7% and 75.2% considered that gastrointestinal intolerance and osteonecrosis of the jaw are linked to BPs,respectively.Conversely,the least recognised complications are ocular inflammation(7.6%) and severe musculoskeletal pain(37.6%).The association of BPs with oesophageal cancer,atrial fibrillation and hepatotoxicity was reported by 11.5%,13.4% and 24.8% of respondents,respectively.The multivariate analysis showed a significant association between level of knowledge and physicians' department affiliation(P-value = 0.043),their gender(P-value = 0.044),whether or not they prescribe a BP(P-value = 0.012),and the number of BP prescriptions delivered monthly(P-value = 0.012).Physicians are mainly concerned about osteonecrosis of the jaw and nephrotoxicity when prescribing a BP.Yet,the complications commonly met in their practice are gastrointestinal intolerance(44.6%) and acute phase reactions(26.7%).CONCLUSION This study revealed the presence of a deficient knowledge regarding BPs-related adverse events among our physicians.Professional training proposals are needed to increase their knowledge and improve their practices.Pharmaceutical industries should reconsider the instructions they provide to physicians regarding the complications of medications they promote.Moreover,they must actively collaborate with education providers and institutions in educational interventions.展开更多
Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old...Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old Caucasian female G2P2, with history of transient osteoporosis of both ankles and C-Section during the last pregnancy in 2011, presented progressively severe bilateral hip pain with onset already in the 12th gestational week. Imaging of the pelvis and bilateral hips with MRI obtained 6 days after the C-Section demonstrated bilateral bone-marrow edema of the hips. The patient was treated with a monthly single dose of 150 mg ibandronate acid per os, for 3 months and physiotherapy. Repeated MRI performed 5 months postpartum revealed a complete remission of the disease. In contrast to the first onset of transient osteoporosis during the first pregnancy, which was only treated conservatively without bisphosphonates, the remission of the disease and patient’s recovery with oral ibandronate therapy showed to be 4 months shorter. This case is unique in literature for both describing the onset of this rare disease twice in the same patient as well as its oral therapeutic approach.展开更多
There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to sear...There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite(HA), this study used three forms of ceramic materials,two of which are bone-stimulating materials, to assess the suitability of new active substances with antiresorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA(a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction(MINE) device(a polymer inert skeleton), respectively, were used. The affinity of risedronate(a standard compound) and sixteen aminomethylenebisphosphonates(new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorptionedesorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.展开更多
Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione ...Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione (TZD) therapy with rosiglitazone and pioglitazone is associated with an increased risk of fractures and decreased bone mineral density (BMD). To our knowledge, no data are available to evaluate bisphosphonate therapy in thiazolidinedione-treated patients. The aim of this study was to investigate the benefit of bisphosphonates to improve changes in BMD in subjects with DM associated with TZDs. Methods: In a cross-sectional observational study using a retrospective review of electronic medical records, the changes in BMD in subjects with type 2 DM. The study subjects were divided into four groups. First group with DM receiving both TZDs and BPs;second group neither;third group receiving only TZDs and the fourth only BPs. The comparison of annual percent changes in BMD between the groups were carried out. Results: Decreased BMD noted in subjects with DM on TZDs. Bisphosphonates improved BMD in subjects with DM on TZDs. BMD improved in subjects with DM in those not receiving TZDs also. Conclusion: We conclude that concomitant treatment with bisphosphonates improves BMD in subjects with diabetes and on TZDs.展开更多
A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the a...A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.展开更多
Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of ...Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of “drug holidays” for bisphosphonates need optimization in order to minimize long-term exposure. Drug holidays may prevent potential adverse events while still maintaining some degree of antifracture efficacy via residual antiresorptive activity by retained bisphosphonates. Patients receiving bisphosphonates, who are at low-moderate risk of fracture, are potential candidates for a drug holiday. However, for high-risk patients or patients with previous history of fragility fractures, the benefits of continuing bisphosphonate therapy considerably out-weigh their potential harm. Evidence-based guidelines regarding starting and stopping a drug holiday are not available;therefore, it is appropriate to monitor patients on a drug holiday to assess a declining antiresorptive effect. In case of a significant rise in bone turnover markers or significant decrease in bone mineral density, it may be time to restart therapy.展开更多
Background Pharmacologic options for treatment of osteolytic diseases especially in children are limited.Although not licensed for use,denosumab,a fully humanized antibody to RANKL,is used in children with good effect...Background Pharmacologic options for treatment of osteolytic diseases especially in children are limited.Although not licensed for use,denosumab,a fully humanized antibody to RANKL,is used in children with good effects.Among others,one possible indication are giant cell tumors and aneurysmatic bone cysts.However,there are reports of severe hypercalcemia during weeks to months after termination of denosumab,that are rarely seen in adults.Methods We collected data of four patients,aged 6-17 years,who experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment.The detailed case information were described.Results One patient was treated with long-term,high-dose steroid therapy,leading to typical Cushing's syndrome.Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop.Finally,in two patients,hypercalcemia ceased definitely after treatment with bisphosphonates.However,several applications were necessary to stabilize calcium levels.Conclusions There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children.Therapeutic and,preferably,preventive strategies are needed.Bisphosphonates seem to be an option for both,but effective proceedings still remain to be established.展开更多
Background： Mineral and bone disorder is one of the severe complications in kidney transplant recipients （KTRs）. Previous studies showed that bisphosphonates had favorable effects on bone mineral density （BMD）. W...Background： Mineral and bone disorder is one of the severe complications in kidney transplant recipients （KTRs）. Previous studies showed that bisphosphonates had favorable effects on bone mineral density （BMD）. We sought to compare different bisphosphonate regimens and rank their strategies. Methods： We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials （CENTRAL） up to April 01, 2017,for randomized controlled trials （RCTs） comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis （NMA） using Bayesian models and assessed the quality of evidence. Results： A total of 21 RCTs （1332 participants） comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium （mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70）. The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate （MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively）. In temas of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium （MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively）. The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best. Conclusions： Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.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 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
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
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
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.
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Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.
文摘Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.
文摘AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital in Beirut city,and its affiliated primary health care center.Data were collected through a new self-administered questionnaire distributed via a delegated secretary to physicians expected to regularly prescribe BPs(n = 215).It assessed participants' knowledge,fear and experience regarding BPsreported complications.RESULTS One hundred and fifty-seven physicians fulfilled the questionnaire(response rate: 73.0%): 77.7% and 75.2% considered that gastrointestinal intolerance and osteonecrosis of the jaw are linked to BPs,respectively.Conversely,the least recognised complications are ocular inflammation(7.6%) and severe musculoskeletal pain(37.6%).The association of BPs with oesophageal cancer,atrial fibrillation and hepatotoxicity was reported by 11.5%,13.4% and 24.8% of respondents,respectively.The multivariate analysis showed a significant association between level of knowledge and physicians' department affiliation(P-value = 0.043),their gender(P-value = 0.044),whether or not they prescribe a BP(P-value = 0.012),and the number of BP prescriptions delivered monthly(P-value = 0.012).Physicians are mainly concerned about osteonecrosis of the jaw and nephrotoxicity when prescribing a BP.Yet,the complications commonly met in their practice are gastrointestinal intolerance(44.6%) and acute phase reactions(26.7%).CONCLUSION This study revealed the presence of a deficient knowledge regarding BPs-related adverse events among our physicians.Professional training proposals are needed to increase their knowledge and improve their practices.Pharmaceutical industries should reconsider the instructions they provide to physicians regarding the complications of medications they promote.Moreover,they must actively collaborate with education providers and institutions in educational interventions.
文摘Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
文摘Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old Caucasian female G2P2, with history of transient osteoporosis of both ankles and C-Section during the last pregnancy in 2011, presented progressively severe bilateral hip pain with onset already in the 12th gestational week. Imaging of the pelvis and bilateral hips with MRI obtained 6 days after the C-Section demonstrated bilateral bone-marrow edema of the hips. The patient was treated with a monthly single dose of 150 mg ibandronate acid per os, for 3 months and physiotherapy. Repeated MRI performed 5 months postpartum revealed a complete remission of the disease. In contrast to the first onset of transient osteoporosis during the first pregnancy, which was only treated conservatively without bisphosphonates, the remission of the disease and patient’s recovery with oral ibandronate therapy showed to be 4 months shorter. This case is unique in literature for both describing the onset of this rare disease twice in the same patient as well as its oral therapeutic approach.
基金supported by the Ministry of Science and Higher Education grants and subsidy of the Ministry of Science and Higher Education。
文摘There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite(HA), this study used three forms of ceramic materials,two of which are bone-stimulating materials, to assess the suitability of new active substances with antiresorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA(a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction(MINE) device(a polymer inert skeleton), respectively, were used. The affinity of risedronate(a standard compound) and sixteen aminomethylenebisphosphonates(new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorptionedesorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.
文摘Objective: Osteoporosis and type 2 diabetes mellitus (DM) two of the most common chronic conditions and represent major public health burdens. Epidemiological and observational studies indicate that thiazolidinedione (TZD) therapy with rosiglitazone and pioglitazone is associated with an increased risk of fractures and decreased bone mineral density (BMD). To our knowledge, no data are available to evaluate bisphosphonate therapy in thiazolidinedione-treated patients. The aim of this study was to investigate the benefit of bisphosphonates to improve changes in BMD in subjects with DM associated with TZDs. Methods: In a cross-sectional observational study using a retrospective review of electronic medical records, the changes in BMD in subjects with type 2 DM. The study subjects were divided into four groups. First group with DM receiving both TZDs and BPs;second group neither;third group receiving only TZDs and the fourth only BPs. The comparison of annual percent changes in BMD between the groups were carried out. Results: Decreased BMD noted in subjects with DM on TZDs. Bisphosphonates improved BMD in subjects with DM on TZDs. BMD improved in subjects with DM in those not receiving TZDs also. Conclusion: We conclude that concomitant treatment with bisphosphonates improves BMD in subjects with diabetes and on TZDs.
文摘A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.
文摘Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of “drug holidays” for bisphosphonates need optimization in order to minimize long-term exposure. Drug holidays may prevent potential adverse events while still maintaining some degree of antifracture efficacy via residual antiresorptive activity by retained bisphosphonates. Patients receiving bisphosphonates, who are at low-moderate risk of fracture, are potential candidates for a drug holiday. However, for high-risk patients or patients with previous history of fragility fractures, the benefits of continuing bisphosphonate therapy considerably out-weigh their potential harm. Evidence-based guidelines regarding starting and stopping a drug holiday are not available;therefore, it is appropriate to monitor patients on a drug holiday to assess a declining antiresorptive effect. In case of a significant rise in bone turnover markers or significant decrease in bone mineral density, it may be time to restart therapy.
文摘Background Pharmacologic options for treatment of osteolytic diseases especially in children are limited.Although not licensed for use,denosumab,a fully humanized antibody to RANKL,is used in children with good effects.Among others,one possible indication are giant cell tumors and aneurysmatic bone cysts.However,there are reports of severe hypercalcemia during weeks to months after termination of denosumab,that are rarely seen in adults.Methods We collected data of four patients,aged 6-17 years,who experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment.The detailed case information were described.Results One patient was treated with long-term,high-dose steroid therapy,leading to typical Cushing's syndrome.Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop.Finally,in two patients,hypercalcemia ceased definitely after treatment with bisphosphonates.However,several applications were necessary to stabilize calcium levels.Conclusions There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children.Therapeutic and,preferably,preventive strategies are needed.Bisphosphonates seem to be an option for both,but effective proceedings still remain to be established.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81570668）.
文摘Background： Mineral and bone disorder is one of the severe complications in kidney transplant recipients （KTRs）. Previous studies showed that bisphosphonates had favorable effects on bone mineral density （BMD）. We sought to compare different bisphosphonate regimens and rank their strategies. Methods： We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials （CENTRAL） up to April 01, 2017,for randomized controlled trials （RCTs） comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis （NMA） using Bayesian models and assessed the quality of evidence. Results： A total of 21 RCTs （1332 participants） comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium （mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70）. The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate （MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively）. In temas of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium （MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively）. The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best. Conclusions： Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.
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 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.
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.
