Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

Bilateral atypical femur fracture in a patient with breast cancer taking zoledronic acid and denosumab: a case report.

A 54-year-old woman developed stage IV breast cancer 8 years prior. Chemotherapy was administered, and she was started on zoledronic acid treatment for her bone metastases. Her chemotherapy regimen was then switched, owing to disease progression. Fifty-seven months after starting treatment with zoledronic acid, the patient suffered an atypical femoral fracture of her right femur, for which she underwent surgery. Twenty months later, she developed another atypical femoral fracture in her left femur and underwent intramedullary nail fixation. Zoledronic acid and denosumab use in patients with metastatic bone tumors caused by breast cancer should be done cautiously, considering atypical femoral fracture risk.

Functional Outcomes of Limb Salvage Surgery in Patients with Giant Cell Tumor of Bone of the Lower Extremities: A Cross-sectional Comparative Study.

Background and Objectives: Giant cell tumor of bone (GCTB) is a benign aggressive tumor primarily treated with surgery. Neoadjuvant treatment with denosumab or zoledronic acid is a common adjunct given to down-stage tumors and facilitate limb sparing surgery. This study sought to determine the characteristics, outcomes, and occurrence of complications following resection (RS) or extended curettage (EC) for GCTB of the lower extremities. Correlation of neoadjuvant therapy with the occurrence of complications was also investigated. Methods: This is an analytical cross-sectional study of 30 patients diagnosed with GCTB of the lower extremity treated between 2015 to 2022 in a single tertiary hospital. Functional outcomes were determined using the 1993 version of the Musculoskeletal Tumor Society (MSTS) score. Mean follow-up for all patients was 2.6 years (SD 1.8). Twenty-two patients (73%) underwent resection, while eight (27%) patients underwent extended curettage. Of the 30 patients, 26 (87%) patients received neoadjuvant therapy, with 21 (81%) given denosumab and five (19%) given zoledronic acid. Results: Functional outcomes were excellent for 23 patients (77%), with no significant difference between RS and EC groups. Nine complications occurred in the RS group, including dehiscence (n=3), superficial infection (n=2), implant failure (n=1), nonunion (n=1), palsy (n=1), and implant irritation (n=1). Five complications occurred in the EC group, four of which were noted to be recurrences, with one case of deep infection. Recurrence was noted to be significantly higher (p=0.0004) in the EC group. Separate correlation analysis showed no significant difference in incidence of complications but found that duration of surgery was significantly longer (p=0.0001), and intraoperative blood loss was significantly higher (p=0.0072) in the RS group. No significant difference (p=0.78) was noted in complication rate between patients given denosumab versus zoledronic acid. Conclusions: Functional outcomes of EC and RS appear to be comparable, including the incidence of complications. However, recurrence was noted to be significantly higher in EC. There appears to be no clear advantage between denosumab or zoledronic acid for GCTB. As a neoadjuvant medication and/or to control tumor progression, zoledronic acid may be the more economic option especially for patients in developing countries.

The effectiveness of intravenous zoledronic acid in elderly patients with osteoporosis after rotator cuff repair: a retrospective study.

The aim of this study was to investigate the effect of zoledronic acid (ZA) on postoperative healing and functional rehabilitation in osteoporotic patients with rotator cuff (RC) injury. 96 Patients were divided into three groups according to bone mineral density and ZA use (Group A: normal BMD; Group B: osteoporosis and intravenous ZA use; Group C: osteoporosis, without ZA use). Radiologic, functional and Serological outcomes were evaluated 6 months after surgery. The functional scores in all groups exhibited significant improvement 6 months after surgery. Inter-group comparison showed that Constant Shoulder joint function Score (CSS) of group A not significantly differing from that of group B, the other indicators were significantly better than those of group B and C. There were no significant differences in shoulder forward flexion, abductive Range of Motion between group B and C. Other indicators of group B were significantly improved compared to group C. The retear rate in group C (30.3%, 10/33) was higher than group A (6.1%, 2/33) and group B (13.3%, 4/30). In conclusion, the application of ZA can significantly reduce the rate of RC retear in elderly patients with osteoporosis after surgery, which is significant for postoperative shoulder joint functional rehabilitation.

Change in body temperature, not acute-phase reaction, predict anti-Osteoporosis efficacy after the first administration of Zoledronic acid: a prospective observational cohort study.

BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.

Hyaluronic acid-covered ferric ion-rich nanobullets with high zoledronic acid payload for breast tumor-targeted chemo/chemodynamic therapy.

Due to the heterogeneity of the tumor microenvironment, the clinical efficacy of tumor treatment is not satisfied, highlighting the necessity for new strategies to tackle this issue. To effectively treat breast tumors by tumor-targeted chemo/chemodynamic therapy, herein, the Fe3+-rich MIL-88B nanobullets (MNs) covered with hyaluronic acid (HA) were fabricated as vehicles of zoledronic acid (ZA). The attained ZA@HMNs showed a high ZA payload (ca 29.6 %), outstanding colloidal stability in the serum-containing milieu, and accelerated ZA as well as Fe3+ release under weakly acidic and glutathione (GSH)-rich conditions. Also, the ZA@HMNs consumed GSH by GSH-mediated Fe3+ reduction and converted H2O2 into OH via Fenton or Fenton-like reaction with pH reduction. After being internalized by 4T1 cells upon CD44-mediated endocytosis, the ZA@HMNs depleted intracellular GSH and degraded H2O2 into OH, thus eliciting lipid peroxidation and mitochondria damage to suppress cell proliferation. Also, the ZA@HMNs remarkably killed macrophage-like RAW 264.7 cells. Importantly, the in vivo studies and ki67 and GPX4 staining of tumor sections demonstrated that the ZA@HMNs efficiently accumulated in 4T1 tumors to hinder tumor growth via ZA chemotherapy combined with OH-mediated ferroptosis. This work presents a practicable strategy to fabricate ZA@HMNs for breast tumor-targeted chemo/chemodynamic therapy with potential clinical translation.

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study-Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury.

Accelerated sub-lesional bone loss is common in the first 2-3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An 'acute interventional cohort' (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A 'chronic non-interventional cohort' (n = 9) with TSCI (duration 1-5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the 'acute' cohort had higher serum CTx, P1NP and sclerostin concentrations, while the 'chronic' cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6-13% at 12 months and ~ 20-23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Clinical Efficacy of Zoledronic Acid on Fracture Reduction in Youth with Primary and Secondary Skeletal Fragility.

CONTEXT: Prior studies have demonstrated the safety and efficacy of zoledronic acid (ZA) to increase bone mineral density (BMD) in children. By contrast, the efficacy of ZA on fractures in the pediatric population remains uncertain. OBJECTIVE: To investigate the effect of ZA on fracture rate in a clinical cohort of children and young adults with skeletal fragility. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: 102 individuals (65 males; 39 with primary and 63 with secondary skeletal fragility) ages 0-21 years old treated with ZA for skeletal fragility between 2010 and 2017. INTERVENTION: ZA was prescribed at discretion of the treating clinician using a standardized protocol. MAIN OUTCOME MEASURES: The primary outcome was change in annualized fracture rate. Secondary outcomes included long bone and spine fracture rates. Areal BMD was analyzed in a subset of individuals with dual energy X-ray absorptiometry (DXA) scans. RESULTS: The overall median fracture rate decreased from 0.6 (IQR: 0.3-1.1) to 0 (IQR: 0-0.4) fractures per year, p<0.001, over a median treatment duration of 1.8 (IQR:0.6-3.0) years. Significant reductions in fracture rate were observed in both primary [1.0 (IQR: 0.6-1.5) to 0.3 (IQR: 0-0.6)] and secondary [0.5 (IQR: 0.1-0.8) to 0 (IQR: 0-0.3)] forms of skeletal fragility, p<0.001 for both. Significant reductions in fracture rate persisted when limited to long bone or long bone plus spine fractures. CONCLUSION: ZA treatment as a component of clinical care was associated with significant declines in fracture rate in this cohort of children and young adults with skeletal fragility.

Efficacy of a single 5 mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.

INTRODUCTION: Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5 mg annual dose for osteoporosis in breast cancer patients, is limited. MATERIALS AND METHODS: In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5 mg dose of zoledronic acid and monitored over 12 months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. RESULTS: Initially, the AI group was the oldest, averaging 59.1 ± 8.7 years. At baseline, no significant differences in variables, except age, were observed. After 12 months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12 months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. CONCLUSION: A single infusion of 5 mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.

The role of protein prenylation inhibition through targeting FPPS by zoledronic acid in the prevention of renal fibrosis in rats.

Renal fibrosis (RF) represents the most widespread pathological condition in chronic kidney disease (CKD). Recently, protein prenylation has been implicated in the fibrosis's progression. The research examined the renoprotective effect of zoledronic acid (ZA) (50 µg/kg/week) in a rat model of carbon tetrachloride (CCl4)-induced RF through targeting protein prenylation. Forty Wistar male rats were split up into the control group, vehicle-treated group, model-RF group, and RF-ZA group. Mean arterial blood pressure (MBP), BUN, serum creatinine, and urine albumin-creatinine ratio (uACR), protein levels of farnesyl pyrophosphate (FPP), tumour necrosis factor-alpha (TNF-α), transforming growth factor-ß (TGF-ß), and malondialdehyde (MDA), and catalase and gene expression of farnesyl pyrophosphate synthase (FPPS) and nuclear factor-kB (NF-κB) were measured. Immunohistochemical staining for renal interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and caspase-3, as well as histopathological alterations, were assessed. ZA considerably ceased the reduction in MBP, markedly reduced uACR, serum creatinine, BUN, and expression of FPPS, FPP, NF-κB, TGF-ß, TNF-α, and MDA, and significantly increased catalase levels compared to the model-RF rats. ZA ameliorated the CCl4-induced histopathological alterations and suppressed the expression of caspase-3, α-SMA, and IL-6. In conclusion, ZA preserved renal function and prevented renal fibrosis in a rat model. These were achieved through targeting protein prenylation mainly by inhibiting FPPS.

Effects of tibolone combined with zoledronic acid on bone density, bone metabolism, and pain in postmenopausal patients with osteoporosis.

OBJECTIVE: To explore the efficacy and safety of tibolone combined with zoledronic acid in the treatment of postmenopausal osteoporosis (PMO). METHODS: We conducted a retrospective analysis of 121 PMO patients from March 2019 to July 2021. Patients were divided into two groups based on treatment regimen: an observation group (n=62) receiving zoledronic acid combined with tibolone and a control group (n=59) receiving tibolone monotherapy. We evaluated and compared therapeutic efficacy, bone mineral density, bone metabolism markers (osteocalcin, serum C-terminal telopeptide of type I collagen, and bone alkaline phosphatase), pain, knee joint function, incidence of fragility fractures, and adverse reactions. Logistic regression analysis was used to evaluate risk factors affecting treatment efficacy. RESULTS: The observation group showed a significantly higher therapeutic effect (96.77%) compared to the control group (83.05%), and a lower incidence of fragility fractures (P=0.012). Before treatment, there were no significant differences in bone mineral density, bone metabolism markers, pain status, or knee function between the two groups (all P>0.05). However, after treatment, evaluations showed marked improvements in these parameters in both groups, with more significant enhancements observed in the observation group (all P<0.001). The incidence of adverse reactions did not significantly differ between the groups (20.97% vs 13.56%, P=0.282). Logistic regression analysis identified the use of tibolone combined with zoledronic acid as a protective factor for effective treatment. CONCLUSIONS: Tibolone combined with zoledronic acid significantly increases bone mineral density, improves bone metabolism, and reduces pain in PMO patients, with a safety profile comparable to that of monotherapy. This regimen should be considered for clinical use in treating PMO.

Zoledronic Acid and Enriched Autologous Bone Marrow Stem Cell Implantation for Femoral Head Osteonecrosis.

Purpose: This study evaluated the clinical results of zoledronic acid in the treatment of early osteonecrosis of the femoral head (ONFH). Materials and Methods: Study retrospectively analyzed 60 patients with zoledronic acid with bone marrow stem cell (BMSC) implantation (The study group) and 64 patients with BMSC implantation (The control group). The primary evaluation index included VAS, HHS, collapsed rate, and total hip replacement arthroplasty (THA) conversion rate. Results: The study group had a lower VAS (1.12 ± 0.22 vs 1.44 ± 0.32) and higher HHS (75.07 ± 3.66 vs 68.78 ± 2.24) compared to the control group in 6 months after surgery (P < 0.05). In the study group, 12 hips (20%) collapsed, and 7 of 60 hips (11.67%) required THA surgery at the last follow-up. However, 25 hips (38.8%) collapsed in the control group, and 19 hips (29.69%) required THA surgery. The study group had a lower collapsed rate (P = 0.029) and THA conversion rate (P = 0.016) in survival analysis. Conclusion: Zoledronic acid and BMSC implantation in the treatment of early ONFH is safe and effective, reduces pain shortens recovery time, and reduces collapsed rate and THA conversion rate in ONFH patients.

First-Line Combination with Proteasome Inhibitor-Based Treatment and Zoledronic Acid Is Effective in Reducing Later Fractures in Multiple Myeloma Irrespective of Multiple Myeloma Bone Disease at Diagnosis.

The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively 345 MM patients treated with autologous stem cell transplantation in Finland during 1996-2020. The median age of the patients was 60 years with a median follow-up time of 50 months (1-339). At diagnosis, 72.1% of the patients had myeloma-associated bone disease and 45.8% had fractures. Most patients (58.8%) received proteasome inhibitor (PI)-containing treatment at first line. MM bone disease was treated in 91.6% of the patients; 49.9% received zoledronic acid (ZA) and 29.9% pamidronate. Inferior overall survival was associated with MM bone disease at diagnosis (p = 0.005) or a fracture at diagnosis (p = 0.003). A later fracture was identified in 29% of the patients, and in those patients without MM bone disease at diagnosis later fractures were less common after ZA treatment (p = 0.049). PI-based treatment plus ZA (p = 0.019) seemed to be the best combination to prevent later fractures, even though the same patient subgroup was more likely to experience relapse (p = 0.018), and also when excluding patients with previous induction therapy without novel agents (p = 0.008). To conclude, this study suggests that the best therapy to prevent later fractures in MM might be PI-based treatment combined with ZA.

Smart Delivery of Biomolecules Interfering with Peri-Implant Repair in Osteoporotic Rats.

Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.

Zoledronic acid relieves steroid-induced avascular necrosis of femoral head via inhibiting FOXD3 mediated ANXA2 transcriptional activation.

BACKGROUND: Zoledronic acid (ZOL) is a type of bisphosphonate with good therapeutic effects on orthopaedic diseases. However, the pharmacological functions of ZOL on steroid-induced avascular necrosis of femoral head (SANFH) and the underlying mechanism remain unclear, which deserve further research. METHODS: SANFH models both in vivo and in vitro were established by dexamethasone (Dex) stimulation. Osteoclastogenesis was examined by TRAP staining. Immunofluorescence was employed to examine autophagy marker (LC3) level. Cell apoptosis was analyzed by TUNEL staining. The interaction between Foxhead box D3 protein (FOXD3) and Annexin A2 (ANXA2) promoter was analyzed using ChIP and dual luciferase reporter gene assays. RESULTS: Dex aggravated osteoclastogenesis and induced osteoclast differentiation and autophagy in vitro, which was abrogated by ZOL treatment. PI3K inhibitor LY294002 abolished the inhibitory effect of ZOL on Dex-induced osteoclast differentiation and autophagy. FOXD3 overexpression neutralized the downregulation effects of ZOL on Dex-induced osteoclasts by transcriptionally activating ANXA2. ANXA2 knockdown reversed the effect of FOXD3 overexpression on ZOL-mediated biological effects in Dex-treated osteoclasts. In addition, ZOL improved SANFH symptoms in rats. CONCLUSION: ZOL alleviated SANFH through regulating FOXD3 mediated ANXA2 transcriptional activity and then promoting PI3K/AKT/mTOR pathway, revealing that FOXD3 might be a target for ZOL in SANFH treatment.

Zoledronic acid for hip fracture during initial hospitalization.

Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remain uncertain. Here we report a cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of all-cause-mortality and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls. A total of 654 patients who had received IP-ZA and 6877 controls (for whom anti-osteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (untreated group), with 71.7% female 92.1% White participants, with a mean age of 80.9 years. Cumulative all-cause mortality over the 24-month follow-up for the IP-ZA group was 12.3% and 20.7% for the untreated group (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78, p < .001). A total of 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = .003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in the IP-ZA group and 5.4% in the untreated group (HR, 0.40; 95% CI, 0.22-0.71, p = .001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs 5.4%; HR, 0.44; 95% 0.24-0.82, p = .008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture.

Hip fracture is a serious complication of osteoporosis affecting approximately 300 000 Americans per year and is associated with a 20%-30% 1-year mortality rate. Most patients with hip fracture are elderly (average age, 80-81 years), with multiple underlying medical conditions and are often unable to timely attend post-hospitalization outpatient follow-up to initiate anti-osteoporosis treatment. As a result, only ~10% of post­hip fracture patients receive treatment for underlying osteoporosis. We have previously reported that zoledronic acid (ZA) administered during initial fracture hospitalization (IP-ZA) is safe and can effectively improve the osteoporosis treatment rate to 70%. The present study analyzed the clinical outcomes of 652 patients who had sustained hip fractures and were treated with IP-ZA and 1926 matched controls and revealed significantly reduced rates of all-cause mortality and vertebral compression fracture (VCF) during a 2-year follow-up period. Of note, nearly 90% of the treated patients received only a single dose of ZA (namely, IP-ZA), suggesting that, for most patients, the only opportunity to receive anti-osteoporosis treatment was during the index fracture hospitalization. Importantly, reduced mortality and VCF rates were readily seen in this single-dose group of patients. Our data suggest that IP-ZA is beneficial for osteoporotic hip fracture.

Efficacy and safety of zoledronic acid in the treatment of osteoporosis: A meta-analysis of randomized controlled trials.

Purpose: Zoledronic acid can inhibit the activity of osteoclasts, and thus, may slow or inhibit bone loss. The purpose of this study was to systematically evaluate the efficacy and safety of zoledronic acid in the treatment of osteoporosis. Methods: Four databases, PubMed, Embase, Cochrane Library, and Web of Science, were systematically searched up to December 26, 2022. The primary outcomes included bone mineral density (BMD), carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal prope-ptide (P1NP), adverse events, and fracture. Secondary outcomes included serum sclerostin level, Visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI). Results: A total of 22 randomized controlled trials were included in this meta-analysis. Meta-analysis results showed that zoledronic acid was effective in increasing BMD of the lumbar spine, femoral neck, trochanter and serum sclerostin level; and reduced CTX, BSAP, P1NP, VAS score, and ODI in patients with osteoporosis. Regarding safety, zoledronic acid could reduce the incidence of fractures but had relatively more adverse events. Conclusion: Zoledronic acid can significantly improve BMD of the lumbar spine, femoral neck and trochanter, and effectively reduce incidence of fracture in patients with osteoporosis, thereby significantly improving patients' quality of life. However, the incidence of adverse events was higher than that of patients treated with placebo.