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Background: A quasi-experimental study was conducted to investigate the clinical efficacy and outcomes of calcitriol combined with bisphosphonates in the treatment of postmenopausal osteoporosis (OP)., Methods: A total of 152 patients with postmenopausal OP from March 2019 to June 2021 were enrolled. The patients who received calcitriol treatment were adopted as the control group, and the patients treated with calcitriol combined with bisphosphonates were considered as the intervention group. The treatment effects of patients were compared, and the pain degree of the joints of the patients was evaluated by Visual Analogue Scale/Score (VAS), the Barthel Index score was used to evaluate the daily living ability of patients, the hand and Oswestry Disability Index (ODI) were used to evaluate the dysfunction before and after treatment, and the bone metabolism indexes, immune cytokines and bone mineral density were detected before and after treatment, and the incidence of adverse reactions was calculated., Results: Regarding the therapeutic effects, the intervention group indicated an effective rate of 96.05% while the effective rate was 84.21% in the control group. The total effective rate of treatment in the intervention group was higher than the control group. The VAS, ODI scores, and bone metabolism indexes of the intervention group were significantly lower than the control group at 1, 2, and 3 months after treatment. The Barthel Index scores and bone mineral density of the intervention group were higher than the control group at 1, 2, and 3 months after treatment. The improvement of immune cytokines in the intervention group was significantly better than the control group (P < .05). One patient in the intervention group developed dizziness and 1 patient developed chills, with an adverse reaction rate of 2.63%, while in the control group, 2 patients had fever, and 2 patients developed chills, with an adverse reaction rate of 5.26% (P > .05)., Conclusion: Calcitriol combined with bisphosphonates has a significant clinical effect in the treatment of postmenopausal OP, which can significantly relieve bone pain in postmenopausal OP patients, enhance abnormal bone metabolism and immune function, and promote bone mineral density and daily living ability., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zoledronic acid is a widely used bisphosphonate for treating osteoporosis and hypercalcemia related to malignancy. It is also used to prevent bone loss induced by cancer treatment and bone metastases in various cancer types. Zoledronic acid is safe for most patients and is generally not associated with severe side effects. However, there have been reports of acute kidney impairment occurring after administration of intravenous zoledronic acid, mostly in patients with cancer (who received a high cumulative dose of this medication) or preexisting kidney impairment, and in patients with a history of nephrotoxic treatment. We report herein the cases of two patients without history of cancer, who developed dialysis-requiring acute kidney impairment after a single administration of intravenous zoledronic acid. None of the patients had previously used nephrotoxic medications, and one of them had a normal kidney function before zoledronic acid treatment. To the best of our knowledge, this report describes the first case of acute kidney impairment in a patient without risk factors. The findings of this report show that acute kidney impairment following intravenous zoledronic acid treatment can also occur in low-risk patients, highlighting the need for monitoring kidney function in all patients receiving this treatment., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Purpose: High-dose denosumab (Xgeva®) is increasingly used for treating bone metastasis and various malignant diseases but carries the risk of medication-related osteonecrosis of the jaw (MRONJ). This study aimed to evaluate the incidence, risk factors, and clinical outcomes of MRONJ in patients treated with high-dose denosumab., Methods: A retrospective review was performed on 1278 patients who received high-dose denosumab at Severance Hospital, Seoul, South Korea, from September 2014 to February 2023. Data on the incidence of MRONJ, patient demographics, primary diseases, and treatment outcomes were analyzed., Results: Among the 1278 patients (average age 64.72 years; 728 males and 550 females) treated, 34 developed MRONJ, with a 2.66% incidence rate. The average age of those with MRONJ was 68.32 years, and they received more Xgeva® injections on average (13.62) compared to the overall cohort. Factors such as age and the frequency of injections were significantly associated with the risk of MRONJ. Notably, the incidence of MRONJ did not significantly differ between those who underwent oral surgery and those with spontaneous MRONJ, especially if oral surgery occurred within 1 month of injection. Surgical interventions have shown higher recovery rates in advanced MRONJ stages., Conclusion: This study confirmed a significant MRONJ incidence of 2.66% among high-dose denosumab recipients, highlighting the importance of careful patient selection, monitoring, and education, particularly in older and long-term treatment patients, to mitigate the risk of MRONJ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Recently, rare cases of medication-related peri-implant osteonecrosis of the jaw (PI-MRONJ) have been reported. In patients with functional implants who begin using anti-osteoporosis medications (AOMs) after implantation, PI-MRONJ is unpredictable and poses a significant threat to the patient. In this study, we aimed to evaluate the impact of AOMs on peri-implant tissues and to examine risk factors for peri-implantitis, a presumed trigger for PI-MRONJ., Methods: The study cohort consisted of patients who underwent implant maintenance treatment between January 2016 and February 2024. Patients were divided into AOM users (AOM group) and controls (control group). Clinical parameters were statistically evaluated, including implant probing depth (iPPD), implant bleeding on probing (iBoP), marginal bone resorption (MBL), and mandibular cortical index (MCI) measured at baseline and at the last visit. Risk factors were examined by multivariate analysis for adjusted odds ratios., Results: A total of 94 patients (35 male, 59 female) with 270 implants were recruited. The AOM group had 93 implants (24 patients). Comparison of clinical parameters showed significantly greater changes in iBoP (p = 0.000768) and MBL (p = 0.000863) scores over time in the AOM group than in the control group. Risk factors for peri-implantitis were a history of moderate or severe periodontal disease (OR: 15.8, 95% CI 3.6-69.3, p = 0.000256) and MCI class 3 (OR: 3.3, 95% CI 1.4-7.8, p = 0.00534)., Conclusions: In implant treatment of AOM users, special attention should be paid to local inflammation, which is presumed to be the cause of PI-MRONJ., (© 2024. The Author(s).)

Background: In the therapy of medication-related osteonecrosis of the jaw (MRONJ), the healing rate, effectiveness of operative therapy, and factors associated with healing remain unclear., Purpose: This study aimed to estimate MRONJ therapy healing rates and identify associated prognostic factors., Study Design, Setting, Sample: A 25-center prospective cohort study was conducted on 291 patients with MRONJ treated with a common therapeutic protocol during 2013-2016. Patients unable to continue examinations or treatment were excluded., Predictor Variable: The primary predictor variable was MRONJ therapy grouped into two categories: operative and nonoperative. Secondarily, the prognostic factors categorized as demographic, medical, clinical, and perioperative were evaluated., Main Outcome Variables: The primary outcome variable was treatment duration, defined as the time (in months) between the initiation of therapy and when the site was healed or the date of the final visit or loss to follow-up., Covariates: Not applicable., Analyses: Descriptive statistics and 3-year cumulative healing rates were calculated. The association between clinical factors and time to healing was analyzed using bivariate and multivariate analyses and propensity score analysis. P < .05 was considered significant., Results: We analyzed data from 291 subjects with 76 (26.1%) and 215 (73.9%) subjects in the operative and nonoperative therapy groups, respectively. The healing rates for operative and nonoperative therapies were 95.8 and 70.7%, respectively (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.1-2.2, P value [P] < .01). The healing rates in patients for whom anti-resorptive agent (ARA) treatment was discontinued and continued were 87.2 and 37.4%, respectively (HR = 1.8, 95% CI = 1.1-3.0, P = .02). In a multiple regression analysis using ARA indication, the therapy method showed a significant association in the MRONJ malignancy group (HR = 2.75, 95% CI = 1.46-5.17, P < .01)., Conclusion and Relevance: Operative therapy and ARA discontinuation were associated with better healing rates in MRONJ therapy. However, the choice of therapy for MRONJ should be based on a comprehensive consideration of the patient's condition. ARA discontinuation should be considered an adjunctive measure because of the possibility of adverse events such as fragility fractures and skeletal related events., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles., Purpose: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis., Methods: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios)., Results: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab., Conclusions: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints., (© 2024. The Author(s).)

Objective: Medication-related osteonecrosis of the jaw bones (MRONJ) is a well-known complication of antiresorptive and antiangiogenic drugs. Since the first report, more occurrences of MRONJ have been described worldwide. Dental extraction has been described by many studies as one of the risk factors for MRONJ. Comprehensive dental care (CDC) is a preventive dental method provided to patients prior to drug commencement. This study aims to determine the association between CDC and MRONJ., Patients and Methods: A retrospective analysis was performed on 75 medical records of patients on antiresorptive and/or antiangiogenic drugs between February 2018 and May 2021. Demographics and clinical and radiographic data were collected. Univariate and multivariate analyses were performed to determine the factors associated with MRONJ., Results: Of the 75 patients who met the inclusion criteria, 11 (14.7%) developed MRONJ. Three out of 11 patients (27.2%) developed MRONJ spontaneously, while eight patients (72.8%) developed it after trauma from dentures or dental extractions. Following a binary logistic regression analysis, the lack of CDC was identified as a significant predictor of MRONJ. Patients who did not receive CDC had an odds ratio of 8.64 (95% confidence interval (CI): 1.27-58.62, p = 0.03). However, dental extraction did not show a statistically significant association with MRONJ in both the univariate and multivariate analyses., Conclusion: CDC before treatment with antiresorptive and antiangiogenic drugs is a potentially effective preventive method for reducing MRONJ. Dental extraction was not a significant factor in relation to MRONJ., (© 2024. The Author(s).)

Background: Bilateral pedicle fractures of the lumbar spine are uncommon and are typically associated with strenuous activities, traumatic events, or previous spinal surgery. This study reported a case of bilateral pedicle fracture in a patient with a long history of osteoporosis treatment with bisphosphonate and included a histological evaluation of the bone., Case Presentation: An 82-year-old woman with no history of trauma presented to our hospital with back pain that had worsened over the previous month. Computed tomography and magnetic resonance imaging revealed bilateral pedicle fractures of the third lumbar vertebra. She had osteoporosis and had been taking bisphosphonates for 9 years. The patient underwent posterior lumbar fusion, and her symptoms improved. Bone biopsy results from the spinous process revealed few osteoblasts and an absence of osteoclasts, indicating low bone turnover., Conclusions: Long-term use of bisphosphonates may contribute to the development of atypical bilateral pedicle fractures in patients with osteoporosis., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Context: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF)., Objective: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined., Methods: This population-based case-cohort study utilized data from the Danish National Healthcare system, including longitudinal records of medication use, healthcare utilization, and x-ray images. Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010 and 2015 (n = 4973) were identified and compared to a random sample (n = 37 021). Bisphosphonate use was collected from 1995-2015. Fracture radiographs (n = 4769) were reviewed by blinded study radiologists to identify AFFs (n = 189) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10., Results: Compared to <1 year of BP use, 5 to 7 years of use was associated with a 7-fold increase in AFF (adjusted HR = 7.29 [CI: 3.07, 17.30]); the risk of AFF fell quickly after discontinuation. The 5-year number needed to harm for one AFF was 1424, while the 5-year number needed to treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure., Conclusion: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Administering zoledronic acid (ZA) to older hip fracture patients during the hospital stay has faced safety concerns. However, in this study of 161 patients, no ZA-related side effects or readmissions were observed, demonstrating that ZA administration during hospitalization is safe and effective for secondary fracture prevention., Purpose: According to the 2022 Dutch 'Osteoporosis and fracture prevention' guideline, zoledronic acid (ZA) is the preferred osteoporosis treatment for hip fracture patients. Less than 25% of hip fracture patients visit the outpatient fracture liaison service, therefore inpatient administration of ZA during the hip fracture hospitalization is now recommended in patients > 75 years. In the OLVG Hospital, inpatient administration of ZA during hospitalization for hip fracture in older patients has been standard of care since 2020., Methods: This single center retrospective observational follow-up study included hip fracture patients > 75 years admitted to the orthogeriatric ward of the OLVG Hospital, and treated with 5 mg of ZA intravenously on the day of hospital discharge between June 2020 and December 2022. Life expectancy estimated < 12 months, creatinine clearance < 35 ml/min, hypocalcemia, and high risk of osteonecrosis of the jaw were contra-indications. During three months of follow-up (FU) adverse events, emergency room visits, hospital readmissions, and death were recorded., Results: In 161 consecutive hospitalized hip fracture patients (mean age 86 ± 6 years, 65% female, 18% nursing home) ZA was administered and no adverse events were recorded. During 3 months of FU, 8 patients (5%) visited the emergency room, 19 patients (12%) were re-admitted to the hospital, 3 with a new fracture (2 contralateral hip, 1 radius), and 17 patients (11%) died of reasons unrelated to ZA., Conclusion: This study shows that inpatient administration of zoledronic acid during hip fracture hospitalization is safe and feasible to prevent future fragility fractures in older hip fracture patients., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background The purpose of this study was to evaluate the outcomes of alveoplasty and primary closure following dental extractions in patients with an elevated medication-related osteonecrosis of the jaw (MRONJ) risk.Study design A retrospective review of 46 patients with an elevated MRONJ risk was conducted. This included a total of 124 teeth extracted, due to unrestorable caries (n = 46; 37%) and peri-apical pathology (n = 44; 35%).Results Our results showed 0% (n = 0) of patients in our cohort developed MRONJ post-operatively. Most patients were being treated with intravenous zoledronic acid for breast cancer (n = 23; 50%), with an average of 15 doses (range 1-72).Conclusions This study supports the use of alveoplasty and primary closure for patients with an elevated MRONJ risk. The authors highlight the importance of pre-operative cone beam computed tomography imaging, optimisation of immune status, post-operative prophylactic antibiotics, and the delay of bone modifying agents recommencement as influential factors in mitigating risk and favouring successful outcomes., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

Long-term bisphosphonate therapy is associated with atypical or insufficiency fractures, particularly in the proximal femur. We observed a case of an atypical femoral shaft fracture in a patient with a long-term history of alendronate therapy. A 36-year-old woman was admitted with a complaint of pain in her right mid-thigh following low-energy trauma. She had been taking alendronate for more than 15 years. X-rays indicated a fracture of the right femoral shaft. The patient was treated with proximal femoral nail antirotation (PFNA) fixation. This case highlights concerns regarding long-term bisphosphonate therapy and its potential complications.

Most participants reported a positive perception of bone active medication despite sustaining a fracture while taking the medication, reporting medication side effects, or having a healthcare provider stop the prescription. Participants did not appear to connect the medication to fracture risk, suggesting this connection should be emphasized by healthcare providers., Objective: Our purpose was to examine perceptions about bone active medication from individuals with a fragility fracture and a prescription for bone active medication., Methods: In this qualitative description study, eligible participants were those who attended an Osteoporosis Canada education session, and reported sustaining a previous fragility fracture and receiving a prescription for bone active medication. We conducted one-on-one interviews and analyzed the data using the analytic hierarchy approach., Results: We interviewed 32 female participants (age range 58-89 years). Based on our analysis, two themes were developed: (1) most participants spoke positively about bone active medication, indicating they were willing to start, or continue to take, their medication. Positive perceptions were held by participants who sustained a fracture while taking bone active medication, participants whose healthcare provider had stopped the prescription, and participants who reported side effects from the medication; (2) most participants did not discuss bone active medication in relation to their fracture and did not appear to connect the medication to the concept of fracture risk. Instead, participants talked about the medication in relation to bone health in general, or to bone density., Conclusion: Participants appeared to have positive perceptions of bone active medication, despite sustaining a fracture while taking the medication, reporting medication side effects, or having a healthcare provider stop the prescription. Participants did not connect bone active medication to the concept of fracture risk, illustrating the need for healthcare providers to emphasize the connection between fracture risk and bone active medication., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Prior to the initiation of intravenous bisphosphonate therapy for osteoporosis, the impact on ocular health is not routinely discussed with patients. This is due to the scarcity of data on the association between bisphosphonates and ocular side effects, resulting in lack of provider awareness to effectively counsel patients. Furthermore, there is little consensus among clinicians on the safety of re-challenging with intravenous bisphosphonate treatment following ocular complications. This is a case report of a patient who developed orbital inflammation four days after receiving a zoledronate infusion. This case was discussed amongst health care providers and osteoporosis experts during a meeting of Bone Health Extension for Community Healthcare Outcomes (ECHO) virtual platform, which was established in 2015., Competing Interests: Declaration of competing interest There are no disclosures or conflicts of interest for Danielle D'Annibale or for Preethika Ekanayake. E. Michael Lewiecki has the following disclosures: Amgen: investigator, consultant, speaker; Radius: investigator, consultant; Kyowa Kirin: consultant, speaker; Ultragenyx: investigator; Angitia: consultant; Ascendis: consultant., (Published by Elsevier Inc.)

We present the first case of concomitant hip and jaw osteonecrosis in a 10-year-old child with aplastic anemia undergoing a transplant. Biphosphonate treatment may be beneficial for hip osteonecrosis but harmful for jaw osteonecrosis. Our experience suggests that clinicians should be cautious when prescribing bisphosphonate to children with simultaneous hip and jaw osteonecrosis. They should be aware of the osteonecrosis locations and treatment choices., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antiresorptive targeted cancer therapies, such as denosumab and bisphosphonates, are used in adults, but their application in pediatric cancer is more recent. Side effects such as osteonecrosis of the jaw (ONJ) observed in adults have curtailed use of these medications in the pediatric population., Purpose: This study assesses the frequency of ONJ, other side effects, and the indications for use of denosumab versus bisphosphonates in pediatric subjects., Study Design, Setting, Sample: A retrospective cohort study of pediatric subjects who underwent bisphosphonate or denosumab therapy at our institution from 2007-2023 was conducted. Subjects aged ≥ 18 years at therapy initiation were excluded., Independent Variable: The independent variable was antiresorptive therapy divided into 2 groups, treatment with intravenous bisphosphonates or denosumab., Main Outcome Variable(s): Primary outcomes were development of bisphosphonate-related and denosumab-related ONJ. Secondary outcomes included additional side effects., Covariates: ONJ risk factors, subject demographics, indications for use, timing, duration, and cumulative dose of antiresorptive therapy were abstracted., Analyses: Univariate and bivariate statistics were computed to describe the sample and measure associations between antiresorptive therapy and outcomes. P values < .05 conferred statistical significance., Results: The sample was composed of 178 subjects with a mean age of 11.7 ± 6.1 years. There were 14 (7.9%) and 164 (92.1%) subjects treated with denosumab and bisphosphonate therapies, respectively. There were 0 cases of ONJ across all subjects. The most common indication for treatment was adjuvant targeted therapy for aggressive tumors and malignancy (39.3%) followed by osteoporosis (14.6%). Subjects treated with denosumab had higher frequencies of hypercalcemia and severe bone pain than subjects treated with bisphosphonates, 28.6% versus 1.2% (P < .001) and 14.3% versus 0.00% (P < .001), respectively., Conclusion and Relevance: While invasive dental procedures are ideally performed before antiresorptive treatment, our data suggest that bisphosphonates may be used safely in the pediatric population with low concern for ONJ. Our data also demonstrated bisphosphonates may have a more tolerable side effect profile than denosumab. If the perceived benefits are similar, we recommend using bisphosphonates as first-line therapy in children while reserving denosumab for refractory cases. Future studies will help determine long-term side effects and differences in efficacies of these medications., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases., Case Presentation: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden., Conclusion: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Bone modifying agents (BMAs) have been used to prevent skeletal-related events (SRE) in cancer patients with bone metastases. In this meta-analysis, efficacy and adverse events (AEs) were studied based on a de-escalation strategy in which the BMA dosing interval was prolonged from 4 to 12 weeks., Methods: PubMed, Cochrane, ICHUSHI, and CINAHL were searched for articles on BMA dosing intervals from outcomes measured were the incidence of SRE and related various AEs. A quantitative meta-analysis was performed using a random-effects model to calculate relative risk ratios (RRs) and 95% confidence intervals (CIs)., Result: The meta-analysis included three randomized controlled studies (RCTs) of Zoledronic acid hydrate (ZA) ( n = 2663) and six RCTs ( n = 141) on BMA other than ZA. There was no difference in the incidence of SREs when comparing the dosing frequency of 12 versus 4 weeks for BMA (RR = 1.21, 95% CI [0.82-1.78], p = 0.33). Further, AEs related to treatment discontinuation were significantly less frequent with ZA given every 12 weeks than when given every 4 weeks (RR = 0.51 [0.30-0.89], p = 0.02). In particular, renal dysfunction leading to grade ≥3 or discontinuation of treatment with ZA occurred significantly less frequently with every 12-week dosing (RR = 0.33 [0.12-0.91], p = 0.33)., Conclusion: This meta-analysis showed no influence of BMA de-escalation on the incidence of SRE; nevertheless, AEs appeared to reduce with the de-escalated usage of ZA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A single-center, randomized, open, 2-period, self-crossover, single-dose trial was conducted to evaluate the bioequivalence of the test (T) and reference (R) preparations in healthy adult female subjects under fasting conditions. Seventy-six subjects were enrolled in the study, and subjects were randomly divided into 2 groups at a 1:1 ratio and were administered once per period, with a 4-day washout period. In each period, plasma drug concentrations, blood calcium changes, and antibodies were determined for pharmacokinetics, pharmacodynamics, and immunogenicity analysis, respectively, and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity were within the predefined bioequivalence criterion of 80%-125%, indicating bioequivalence between the T and R preparations under fasting conditions. Comparable serum calcium levels demonstrated pharmacodynamics similarity, and no differences were found in immunogenicity profiles. Additionally, the incidence of adverse reactions to the T preparation was 18.4% lower than that of the R preparation (31.6%). This study confirmed the bioequivalence of the T and R preparations under fasting conditions, along with comparable immunogenicity profiles and good safety., (© 2024, The American College of Clinical Pharmacology.)

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1 , VEGFA , and CYP2C8 . With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.

Introduction: Zoledronic acid (ZA), used for treatment of children with osteoporosis, can cause acute phase reaction (APR) following the first infusion. Many institutions have a policy to admit and monitor all children for their first ZA infusion., Objective: To determine if the APR with the first ZA dose warrants hospital-level care and evaluate if its severity correlates with the underlying condition., Design: Retrospective cross-sectional analysis., Settings: Two tertiary centres across the UK that run paediatric metabolic bone disease services., Patients: Children who received first ZA infusion as inpatients at these centres., Interventions: Nil., Main Outcome Measures: The Paediatric Early Warning Score (PEWS) and length of hospital stay to assess the severity of APR., Results: 107 patients were included. Peak PEWS≤3 was found in 85% of children. 83% required admission for <24 hours. The various patient populations (osteogenesis imperfecta (OI), immobility-induced osteoporosis, idiopathic juvenile osteoporosis, systemic inflammatory disorders and steroid-induced osteoporosis, Duchenne muscular dystrophy (DMD)) did not differ significantly in the mean peak PEWS and the length of hospital stay. However, when compared directly, the group with DMD and that with systemic inflammatory disorders and steroid-induced osteoporosis differed significantly in the mean peak PEWS (p=0.011) and the length of hospital stay (p=0.048), respectively, as compared with the OI group., Conclusion: Most patients had a mild APR not requiring overnight hospital admission, after their first ZA dose. However, certain groups seem to suffer more severe APR and may warrant consideration of inpatient monitoring with the first infusion., Competing Interests: Competing interests: SCW received funding from Novartis in 2017 for a one-off consultancy meeting regarding zoledronate., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The study found that in osteoporosis patients who had not previously received bisphosphonate treatment and were in a treatment cycle of over 12 months, both teriparatide and denosumab significantly increased bone mineral density compared to bisphosphonates. Additionally, teriparatide was also shown to significantly decrease the risk of fractures., Objective: The systematic review and meta-analysis aimed to assess and compare the safety and efficacy of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in patients with osteoporosis who had not previously received bisphosphonates., Methods: We conducted a search of published literature from inception to May 31, 2023, including databases such as PubMed, Embase, Cochrane Library, CNKI, SinoMed, VIP, and WanFang. The study only included head-to-head randomized controlled trials (RCTs) that compared teriparatide and denosumab with bisphosphonates to treat patients with osteoporosis. Fixed-effect model and random-effect model were used due to clinical heterogeneity. Meta-analysis was performed via Stata 17.0., Results: A total of 6680 patients were enrolled across 23 eligible trials. The results of the meta-analysis showed that teriparatide was superior to bisphosphonates in decreasing the risk of fracture (risk ratio (RR) = 0.61, 95% confidence interval (CI) (0.51, 0.74), P < 0.001). Denosumab showed no benefit compared to bisphosphonates in reducing the risk of fracture in treating osteoporosis (RR 0.99, 95% CI (0.62, 1.57), P = 0.96). Compared with bisphosphonates, teriparatide and denosumab could significantly improve femoral neck, total hip, and lumbar spine bone mineral density (BMD) (P < 0.05). Furthermore, teriparatide and denosumab did not increase the incidence of adverse events (teriparatide vs. bisphosphonates, RR 0.92, 95% CI (0.79, 1.08), P = 0.32; denosumab vs. bisphosphonates, RR 0.98, 95% CI (0.95, 1.02), P = 0.37)., Conclusions: Teriparatide is superior to bisphosphonates in decreasing the risk of fracture in patients with osteoporosis. In addition, teriparatide and denosumab were more efficacious than bisphosphonates in increasing the percentage change in BMD at the femoral neck, total hip, and lumbar spine., (© 2024. The Author(s).)

Rationale: Denosumab, a fully humanized IgG monoclonal antibody, is commonly employed in the management of different types of osteoporosis. Up to now, hypocalcemia linked with denosumab has been predominantly reported in dialysis patients suffering from chronic kidney disease. Interestingly, there have been no reports of hypocalcemia following craniopharyngioma surgery with the use of denosumab., Patient Concerns: A 65-year-old male received a subcutaneous injection of denosumab (60 mg) as a treatment for osteoporosis following the resection of a craniopharyngioma. Remarkably, the patient developed hypocalcemia within 4 days post-injection. However, 6 months subsequent to the initial treatment, the patient underwent another subcutaneous injection of desmuzumab and once again experienced hypocalcemia., Diagnoses: Hypocalcemia., Interventions: The hypocalcemia was successfully managed with intravenous calcium gluconate and oral calcium carbonate D3 tablets, leading to the alleviation of symptoms., Outcomes: Hypocalcemia following the use of denosumab after craniopharyngioma surgery is rare, and its occurrence may be associated with the primary disease and concomitant medications., Lessons: It underscores the necessity for clinicians to perform a thorough evaluation of the patient's overall health status, complete all requisite testing, pay particular attention to those in high-risk categories, and ensure serum calcium levels are monitored, along with conducting other essential tests, prior to and following each administration of denosumab., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: A systematic review and Meta-analysis., Objective: To compare the efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis., Summary of Background Data: While bisphosphonates have historically been the cornerstone of pharmacological management for bone protection in patients, emerging evidence suggests that teriparatide and denosumab warrant further investigation as potential first-line treatments. The optimal choice among denosumab, teriparatide, and oral bisphosphonates for the treatment of postmenopausal osteoporosis remains a subject of ongoing debate and controversy within the scientific community., Methods: This systematic review adhered meticulously to the rigorous standards outlined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines as well as the Cochrane Collaboration recommendations. Additionally, it employed the AMSTAR (Assessing the methodological quality of systematic reviews) criteria to ensure methodological robustness and enhance the credibility of the findings. A systematic electronic search was conducted across Web of Science, PubMed, and the Cochrane Library databases from their inception dates up to February 2024., Results: In this meta-analysis of studies, our findings suggest that compared to bisphosphonates, both teriparatide and denosumab demonstrated notable increases in percentage changes in lumbar spine bone mineral density (BMD) among postmenopausal osteoporosis patients. Furthermore, denosumab exhibited superiority over teriparatide and oral bisphosphonates in enhancing percentage changes in both femoral neck and total hip BMD, indicating its potential as a more efficacious option. Regarding safety outcomes, no significant differences were observed in the incidence of serious adverse events among patients treated with teriparatide, denosumab, and bisphosphonates. However, teriparatide showed superiority over oral bisphosphonates in terms of a lower risk of general adverse events, suggesting a favorable safety profile., Conclusion: In conclusion, our study suggests that teriparatide and denosumab demonstrate comparable or potentially superior efficacy and safety profiles compared to oral bisphosphonates for the treatment of postmenopausal osteoporosis., Systematic Review Registration: PROSPERO, identifier CRD42024508382., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Guo, Cui, Guo and Dong.)

Introduction: Atypical femoral fractures (AFFs) are a rare type of subtrochanteric or diaphyseal fracture frequently associated with the use of bisphosphonates (BPs). They are a clinical entity often overlooked, for which a correct clinical-instrumental classification is essential for a successful treatment. Nowadays, there is no accurate data on their real incidence. The aim of this work is to evaluate the period prevalence of AFFs and their risk factors, and to compare actual results with a previous study conducted at the same Institution seven years previously., Materials and Methods: The same methodology used in the previous study, conducted by the same Authors, was applied. Radiographs of all subtrochanteric and diaphyseal femoral fractures in patients over 60 years treated at a single Institution between January 2018 and February 2020 were reviewed, and cases that displayed the AFFs definition criteria were identified. Current and previous medical and pharmacological history were collected, and osteometabolic evaluation through the execution of first level blood tests, with the addition of a valuation of 25(OH)-vitamin D and parathormone was performed., Results: Out of 40 subtrochanteric or diaphyseal femoral fractures in patient aged 60 years or older, four cases (10 %) presented a characteristic radiographic pattern significative for AFFs, in comparison with a 5 % observed in the previous study. All four patients were women with a positive (current or previous) history of BPs consumption., Discussion: The efficacy of BPs for the prevention of osteoporotic fractures is widely demonstrated. However, particularly prolonged use of these drugs may increase the risk of developing AFFs in some patients. The incidence of AFFs is higher than that reported in the literature, if evaluated only for the subtrochanteric and diaphyseal sites (essential diagnostic criterion in the definition of AFFs). In our study, the incidence of AFFs doubled after seven years. The present data also confirm the frequent association between the use of BPs and the onset of AFFs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Denosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis., Areas Covered: Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab., Expert Opinion: Although bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.

This was a Phase I, randomized, double-blinded, three-arm, single-dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU-reference] and United States [US-reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC 0-last ); and maximum observed serum concentration (C max ). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC 0-∞ ), time to reach maximum observed concentration, clearance, terminal phase half-life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. C max was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half-live across treatment arms. Systemic exposure of MB09 (AUC 0-last and C max ) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C-terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment-emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products., (© 2024 mAbxience Research SL. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture., Materials and Methods: In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs)., Results: The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4% vs 72.6% in the 1/D-TPTD and 2/W-TPTD groups, respectively), distributions of overall satisfaction scores, and satisfaction with treatment (p > 0.05) were observed. However, several items of satisfaction with the utility of the injection device were significantly higher in the 2/W-TPTD group (p < 0.05). Statistical improvements from baseline values were observed in QOL and pain VAS in both groups (p < 0.05). No serious AEs were reported., Conclusion: The between-group similarity of overall treatment satisfaction and effectiveness scores and between-group difference in satisfaction with the utility of the self-injection device was useful information for real-world treatment of osteoporosis. Both medication regimens were well tolerated., (© 2024. The Author(s).)

Introduction: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis., Materials and Methods: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated., Results: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months., Conclusion: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions)., (© 2024. The Japanese Society Bone and Mineral Research.)

Introduction: Denosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon., Case Presentation: We present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed., Discussion: Our clinical case illustrates the ineffectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option., (Copyright © 2024 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: This retrospective cohort multicentre study aimed to characterise the signalment, clinicopathologic data, complications and the association between treatment and outcome (the reduction in ionised calcium concentration) in cats with idiopathic or chronic kidney disease-associated ionised hypercalcaemia managed with alendronate and standard treatment or standard treatment alone, and to compare the outcome between the two groups., Materials and Methods: Medical records for cats diagnosed with idiopathic or chronic kidney disease-associated ionised hypercalcaemia were retrospectively reviewed. Cats treated with alendronate and standard treatment were assigned to the alendronate group and cats treated with standard treatment alone were assigned to the control group. The standard treatment was defined as dietary modification and/or monitoring of ionised calcium concentrations and management of complications secondary to hypercalcaemia. The follow-up period was selected as 6 months., Results: Twenty-nine cats were enrolled in the study. Nine cats were included in the control group and 20 cats in the alendronate group. A significant reduction in serum ionised calcium was observed in both groups between the baseline and the follow-up visit; however, this reduction did not differ significantly between both groups (the mean change in the ionised calcium concentration in alendronate and control group was -0.18 and -0.17, respectively). Suspected bisphosphate-related osteonecrosis of the jaw was reported in one cat receiving alendronate., Clinical Significance: In this study, similar reduction in serum ionised calcium concentration was observed in cats with ionised hypercalcaemia treated with diet alone and in cats treated with diet and alendronate. These results should be interpreted with caution, as the study was underpowered for meaningful statistical comparison. Cats receiving alendronate should be monitored for the development of adverse reactions, including osteonecrosis of the jaw., (© 2024 British Small Animal Veterinary Association.)

Purpose: Medication-related osteonecrosis of the jaws has been reported to be associated with bisphosphonate and RANKL inhibitor medications. This prospective clinical study aimed to assess the outcomes of pre-operative ozone infiltration therapy in patients with established MRONJ., Methods: The treatment protocol for ozone applications were designed as 20 applications ozone infiltration therapy followed by surgical interventions of necrotic tissue debridement using piezoelectric surgery instruments. The evaluation of the results based on the clinical and radiologic specifications considering the necrotic lesion reduction and healing. The study included 31 lesions in 29 patients. The mean follow-up was 23.6 months., Results: 25 lesions out of 31 healed totally without any remissions. The outcomes were not affected by any variables such as gender, age, type of pharmacological treatment, lesion location, and MRONJ staging. The statistically significant results were found among the clinical condition of the patients (p = 0.01) and administration route of medications (p = 0.004). Healing was significantly less in patients that received intra-vascular administrations. Clinical conditions of the patients were divided as osteoporosis, oncologic, and arthritis. Significantly better results were obtained in osteoporosis patients. 38% of the population experienced spontaneous sequestration with signs of improvements and the surgical interventions were canceled. According to the results, total healing of MRONJ lesions was seen in 79% patients (81% lesions)., Conclusion: Ozone therapy and debridement with Piezoelectric surgery can be considered as a safe and beneficial adjunctive treatment alternative for osteonecrosis lesions in cases of established MRONJ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse illness linked to antiresorptive therapies (ART), for which there is no therapeutic gold standard. Many factors can influence MRONJ evolution such as cancer type, treatment, comorbidities, and accumulated dose of ART. The aim of this study was to determine the influencing factors of MRONJ treatments success., Methods: This retrospective study focused on patients treated for MRONJ in a French tertiary centre. Non-operative therapy was always applied, ART were suspended if appropriate, and surgery (MRONJ removal and musculo-mucosal flap reconstruction) was performed in the absence of contraindication. The evaluation criteria were bone and mucosal healing 3 months after surgery., Results: 81 MRONJ were included; medical treatment alone was administered to 26 % while the remaining 74 % received additional surgery. Therapeutic success reached 86.7 % (52/60) for surgery compared to 42.9 % (9/21) for medical treatment alone (p < 0.001). Age (OR=1.08, p = 0.014) and the absence of infection (OR=5.32, p = 0.042) were in favour of success, while medical treatment alone (OR=0.03, p < 0.001) was highly unfavourable., Conclusion: MRONJ healing is influenced by age, non-infectious stages, and surgery. Additional surgery in MRONJ treatment should be advised if the health of the patient permits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aim: To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis., Methods: A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools., Results: Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I 2  = 10.76%)., Conclusions: This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12 months of romosozumab therapy. The study had an observational pre-post design and included 460 patients. Romosozumab was administered at a dose of 210 mg subcutaneously every 4 weeks for 12 months. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 11 cases (3.0 %). Nine patients (2.0 %) experienced cardiovascular events, which were fatal in 3 (0.65 %). Percent changes in BMD at the spine and total hip at 12 months from baseline were +7.7 % and +1.8 %, respectively. Romosozumab had better effects in patients with good renal function, low spine BMD, and high TRACP-5b at baseline and low TRACP-5b or high P1NP after 1 month of treatment. The percent change in spine BMD at 12 months was significantly lower in patients transitioning from denosumab than in those not previously treated with other anti-osteoporosis agents. Romosozumab is considered to be relatively safe in patients with primary osteoporosis compared to those with secondary osteoporosis. Romosozumab resulted in larger increases in spine BMD in patients with primary osteoporosis who were not previously treated with other anti-osteoporosis therapies and those with low spine BMD at the start of treatment., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research., Data: This review used the PCC strategy (P = Patient; C = Concept; C = Context)., Sources: The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used., Study Selection: Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4 %) were in animals, and 103 (58.5 %) were in humans. Brazil led in animal studies (n = 14; 19.1 %), while Italy led in human studies (n = 14; 13.6 %). Zoledronic acid was the most cited BF (79.4 % in animals; 34.9 % in humans), with intravenous administration being most frequent (38.3 % in animals; 35.9 % in humans). The mandible was the main extraction site (n = 36 in animals; n = 41 in humans). In 91.7 % of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n = 39; 53.4 %). In humans, 93.2 % of studies presented 239 sequelae, with bone necrosis (n = 53; 22.1 %) being the most cited. The main location of sequelae was the mandible (n = 36 in animals; n = 41 in humans)., Conclusions: Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy., Clinical Significance: These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ., Competing Interests: Declaration of competing interest The authors declare that there were no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1-3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Tori and exostoses are considered risk factors for the development of medication-related osteonecrosis of the jaw (MRONJ). The aims of this study were to present the prevalence of MRONJ located at tori in the Copenhagen ONJ Cohort, evaluate the surgical treatment of MRONJ located at tori and explore trauma to tori as an additional risk factor in patients on antiresorptive medication., Methods: Data from a consecutive series of 506 patients with MRONJ (Copenhagen ONJ Cohort) were reviewed for the presence of tori and MRONJ located at tori. Demographic and medical data were analyzed, and healing outcomes and pain after the prophylactic removal of tori, surgical treatment of MRONJ located at tori, and conservative treatment of MRONJ located at tori were evaluated and compared using Fisher's exact test., Results: MRONJ located at tori was frequent and could be identified in 53% of the patients with tori, which accounts for a prevalence of 5.1% in the entire cohort. Of the 28 surgically treated patients, 27 (96.4%) healed uneventfully with no exposed bone after their first or second revision surgery. Fourteen (41.2%) patients with tori underwent therapeutic removal, eight (23.5%) underwent prophylactic removal, and six (17.6%) underwent both therapeutic and prophylactic removals. Two (33.3%) of the six conservatively treated patients healed spontaneously. Both treatment types resulted in a significant decrease in pain., Conclusion: Prophylactic and therapeutic surgical removal of tori are reliable treatments and should be considered if a patient's general health allows surgery., Trial Registration: The study was approved by the Regional Scientific Ethical Committee (H-6-2013-010) on November 20, 2013, and was retrospectively registered., (© 2024. The Author(s).)

Background: Certain medications interfere with the bone remodeling process and may potentially increase the risk of complications after total knee arthroplasty (TKA). As patients undergoing TKA may be taking these bone mineral density (BMD)-reducing medications, it is unclear as to whether and which medications impact TKA outcomes. Therefore, the purpose of this study was to observe the impact of various BMD-reducing medications on 2-year implant-related complications following TKA., Methods: A retrospective analysis of patients undergoing primary TKA was conducted using a national administrative claims database. Patients were identified if they were taking any known BMD-reducing medication and were compared to control patients. To control for confounders associated with taking multiple agents, multivariable logistic regression analyses were conducted for each 2-year outcome (all-cause revision, loosening-indicated revision, and periprosthetic fracture--indicated revision), with the output recorded as odds ratios (ORs)., Results: In our study, 502,927 of 1,276,209 TKA patients (39.4%) were taking at least one BMD-reducing medication perioperatively. On multivariable analysis, medications associated with a higher likelihood of 2-year all-cause revision included first- and second-generation antipsychotics (SGAs) (OR: 1.42 and 1.26, respectively), selective serotonin reuptake inhibitors (SSRIs) (OR: 1.14), glucocorticoids (1.13), and proton pump inhibitors (PPIs) (OR: 1.23) (P < .05 for all). Medications associated with a higher likelihood of 2-year periprosthetic fracture included SGAs (OR: 1.51), SSRIs (OR: 1.27), aromatase inhibitors (OR: 1.29), and PPIs (OR: 1.42) (P < .05 for all)., Conclusions: Of the drug classes observed, the utilization of perioperative PPIs, SSRIs, glucocorticoids, first-generation antipsychotics, and SGAs was associated with the highest odds of all-cause revision. Our findings suggest a relationship between these medications and BMD-related complications; however, further studies should seek to determine the causality of these relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8 weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients., Purpose: The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice., Study Design, Setting, Sample: We designed a randomized in-vivo animal study utilizing male and female mice treated with zoledronic acid (ZA). Experimental periodontitis was induced in 24 male and 24 female mice using a silk ligature following administration of saline or a potent bisphosphonate. After 8 weeks, animals were evaluated radiographically and histologically., Independent Variable: The independent variables were sex (male vs female) and treatment group (ZA vs saline control). Treatment was randomly assigned with balanced distribution between male and female animals., Main Outcome Variable: The main outcome variable was ONJ status coded as present or absent. ONJ was defined as present if there was histologic contact between the ligature and the alveolar bone. Secondary outcomes of interest were radiographic and histologic parameters., Analysis: Statistical differences were analyzed using a two-way analysis of variance with Tukey's post hoc test using a P value of 0.05 for significance., Results: The final sample was composed of 24 vehicle treated and 24 ZA treated animals. In vehicle treated animals, 8% of female and 8% of male animals developed ONJ. In ZA treated animals, 83% of female and 92% of male animals developed ONJ. Sex was not associated with the risk (measured as incidence of disease) for developing ONJ or in the radiographic or histologic parameters that were assessed (P values >.1)., Conclusions: Sex does not appear to affect the incidence of MRONJ or the severity of the disease as assessed by the radiographic and histologic parameters., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze the communication between doctors and patients who were taking bone-stabilizing medication and in rare cases developed osteonecrosis of the jaw as a result., Material and Methods: A standardized questionnaire recorded deficits based on patient experiences. These data were used to develop solution strategies for improving doctor-patient communication and the benefit-risk assessment of medication use., Results: Most patients were satisfied with the information provided by their doctor; however, one in three (29.8%) were not informed about possible side effects, and a quarter (24.6%) only found out about osteonecrosis of the jaw through their own research. Only half (45.7%) were asked about risk factors, and most information materials were rated poorly. The diagnosis took an average of 18.7 months, with many (47.8%) consulting a doctor only when they experienced pain. Quality of life was severely impaired, with daily pain, physical limitations, and negative effects on mental health. About a third (35.3%) reported that their quality of life had deteriorated significantly., Conclusions: Further research into patient education is necessary. Web-based information brochures, improved follow-up care, and close cooperation with dentists are required. The use of a running sheet, such as the AGSMO running sheet, for individual risk assessment of osteonecrosis of the jaw is recommended. Patients undergoing treatment with bone-stabilizing medication should be monitored closely. Education about osteonecrosis of the jaw must be continued, and the medical profession must be confronted with it., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)