Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature.

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.

Medication-related osteonecrosis of the jaw: Case series and literature review.

Key Clinical Message: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare complication of the jaws following the administration of antiresorptive or antiangiogenic drugs. This condition poses a major challenge to its management. Its prevention and management need a multidisciplinary collaboration. We described three patients with MRONJ including their presentation, investigations, management protocols, and outcomes. A brief appraisal of the literature on MRONJ was also done. Abstract: Medication-related osteonecrosis of the jaw (MRONJ) is a rare complication of the jaws following the administration of antiresorptive or antiangiogenic drugs. This condition poses a major challenge to its management. We present an appraisal of the literature and three cases of MRONJ. An appraisal of 3 patients who presented to the oral and maxillofacial clinic with MRONJ was done. Relevant physical examination findings, radiological images, clinical photographs and follow-up was documented. One patient had multiple myeloma while the other two had metastatic cancer. All had received zoledronic acid before developing MRONJ. One patient was surgically treated and successfully recovered while two were managed conservatively. Patients taking antiresorptive medications are at risk of developing MRONJ. Prevention and management of the condition calls for a multidisciplinary collaboration. Patients taking antiresorptive medications need good education on the risks associated with the medications and how to recognize early signs and symptoms.

Effectiveness of Pamidronate Infusion in the Treatment of Charcot Arthropathy.

Introduction: The objective of this case series is to investigate the efficacy and safety of intravenous infusion of Pamidronate, a second generation bisphosphonate, in the treatment of active Charcot arthropathy. Materials and methods: All patients with active Charcot arthropathy treated at the medical centre from 1 January 2013 to 30 June 2020 were included in the study. Efficacy outcome was evaluated based on time to consolidate findings observed through radiographic examination, while safety outcome was evaluated based on the incidence of adverse event (AE) occurrence. Results: A total of 81 patients (37 male, 44 female) diagnosed with active Charcot arthropathy were included. 64.2% of patients were at stage 1 of Charcot arthropathy whereas 35.8% were at stage 2. The mean time to consolidate for stage 1 and stage 2 was 6.50 ± 4.21 months and 3.63 ± 2.92 months respectively (p-value = 0.139). No significant association was observed between gender, ethnicity and disease stage with the consolidation time (p-value >0.05). The rate of AE incidence was 2.5%, observed in 2 patients who developed a fever during the treatment. No other serious AE was observed in the study. Conclusion: Intravenous Pamidronate infusion is a safe and effective treatment option for Charcot arthropathy.

Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin-methacrylated hyaluronic acid-poly (ethylene glycol) diacrylate (GHP) macroporous hydrogel to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in-situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration. This article is protected by copyright. All rights reserved.

Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study.

Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites. One hundred twenty had previously been randomized to zoledronate (19 doses of 4 mg over 5 yr) and 104 to the control arm. BMD and BTMs were assessed at sub-study entry, 6 (BTMs only), 12, 24, and 60 mo following the completion of AZURE. As expected, mean BMD, T-scores, and Z-scores at sub-study entry were higher in the zoledronate vs the control arm. At the lumbar spine, the mean (SD) standardized BMD (sBMD) was 1123 (201) and 985 (182) mg/cm2 in the zoledronate and control arms, respectively (P < .0001). The baseline differences in sBMD persisted at all assessed skeletal sites and throughout the 5-yr follow-up period. In patients completing zoledronate treatment, BTMs were significantly lower than those in the control arm (α- and ß-urinary C-telopeptide of type-I collagen, both P < .00001; serum intact pro-collagen I N-propeptide, P < .00001 and serum tartrate-resistant acid phosphatase 5b, P = .0001). Some offset of bone turnover inhibition occurred in the 12 mo following the completion of zoledronate treatment. Thereafter, during the 60 mo of follow-up, all BTMs remained suppressed in the zoledronate arm relative to the control arm. In conclusion, in addition to the known anti-cancer benefits of adjuvant zoledronate, there are likely to be positive, lasting benefits in BMD and bone turnover.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Fatality owing to pulmonary hemorrhage following pamidronate disodium administration in a neonate with osteogenesis imperfecta type 2: A case report.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

Fibrous dysplasia of the head and neck in Southern Finland: a retrospective study on clinical characteristics, diagnostics, and treatment.

PURPOSE: Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. METHODS: A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005-2020. RESULTS: In total 74 patients were identified; 54% were male and the mean age 45 years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. CONCLUSION: Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities.

Role of bisphosphonates in hypertrophic osteoarthropathy: a systematic review.

BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Zoledronic Acid Supplementation With Excision of a Giant Cell Tumor of the Distal End Radius to Prevent Recurrence: A Case Report.

Giant cell tumors are benign yet locally aggressive neoplasms commonly observed in the distal radius, exhibiting higher recurrence rates compared to other tumor types. This study presents a case involving a 50-year-old farmer who presented with swelling at the distal end of his wrist. The patient underwent treatment involving intralesional curettage and supplementation with zoledronic acid, resulting in a significant reduction in the tumor's potential for recurrence. This approach aims to achieve an optimal balance between functional outcomes and disease management in the majority of cases. While this strategy proves effective in most instances, there may be scenarios where resection becomes imperative due to the severity of the disease, ensuring adequate disease clearance. In such circumstances, judicious decision-making coupled with an appropriate treatment plan is crucial to guarantee a satisfactory outcome, even in the face of challenges.

The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

Management of cancer treatment-induced bone loss in patients with breast and hormone sensitive prostate cancer: AIOM survey.

PURPOSE: Cancer treatment-induced bone loss is a side effect of hormonal therapy that can severely affect patients' quality of life. The aim of this survey was to obtain an updated picture of management of bone health in patients with breast cancer undergoing adjuvant hormonal therapy and in patients with hormone sensitive prostate cancer according to Italian oncologists. METHODS: Our survey was made up of 21 multiple-choice questions: the first part dealt with the respondents' characteristics, while the second with management of bone health in the described setting. An invitation to complete the survey was sent by e-mail to 2336 oncologists, members of Italian Association of Medical Oncology, in October 2022. RESULTS: Overall, 121 (5.2%) Italian oncologists completed the survey. In most cases (57%) the oncologist personally took charge of the management of bone health in patients at risk for cancer treatment-induced bone loss. At the beginning of hormonal therapy, most respondents reported to require bone health diagnostic exams, such as dual-energy X-ray absorptiometry (89%), repeated with different timing. Main reported reasons (not mutually exclusive) for prescribing antiresorptive drugs were modifying fracture risk (87%), densitometry values (75%) or prognosis (34%). Answers about the management of antiresorptive therapy were heterogeneous. CONCLUSION: A heterogeneous approach on the management of cancer treatment-induced bone loss in Italy arises from this survey. This scenario highlights the need for a major consensus of the Italian scientific community on the diagnostic and therapeutic approach of cancer treatment-induced bone loss and for a greater awareness of this topic among Italian oncologists.

Pediatric and adult osteoporosis: a contrasting mirror.

Pediatric osteoporosis (PO) is a condition that is currently gaining recognition. Due to the lack of official definitions over the past few decades, the exact incidence of PO is unknown. The research does not provide a specific prevalence of PO in different world regions. However, this is expected to change with the latest 2019 guidelines proposed by the International Society of Clinical Densitometry. Although adult osteoporosis (AO) has been postulated a pediatric disease because its manifestation in adulthood is a result of the bone mass acquired during childhood, differences between PO and AO should be acknowledged. AO is defined as low bone density; however, PO is diagnosed based on existing evidence of bone fragility (vertebral fractures, pathological fractures). This is particularly relevant because unlike in adults, evidence is lacking regarding the association between low bone density and fracture risk in children. The enhanced capacity of pediatric bone for reshaping and remodeling after fracture is another difference between the two entities. This contrast has therapeutic implications because medication-free bone reconstitution is possible under certain conditions; thus, background therapy is not always recommended. In this narrative review, differences between PO and AO in definition, assessment, and medical approach were investigated.

Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.

Bacillus Calmette-Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored their effects on trained immunity induced by BCG in a placebo-controlled clinical study (NL74082.091.20) in young, healthy individuals. Participants receiving single-dose oral alendronate on the day of BCG vaccination had more neutrophils and plasma cells one month after treatment. Alendronate led to reduced proinflammatory cytokine production by PBMCs stimulated with heterologous bacterial and viral stimuli one month later. Furthermore, the addition of alendronate transcriptionally suppressed multiple immune response pathways in PBMCs upon stimulation. Our findings indicate that N-BPs modulate the long-lasting effects of BCG vaccination on the cytokine production capacity of innate immune cells.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Synthesis and preliminary anticancer evaluation of photo-responsive prodrugs of hydroxymethylene bisphosphonate alendronate.

The antitumoral activity of hydroxymethylene bisphosphonates (HMBP) such as alendronate or zoledronate is hampered by their exceptional bone-binding properties and their short plasmatic half-life which preclude their accumulation in non-skeletal tumors. In this context, the use of lipophilic prodrugs represents a simple and straightforward strategy to enhance the biodistribution of bisphosphonates in these tissues. We describe in this article the synthesis of light-responsive prodrugs of HMBP alendronate. These prodrugs include lipophilic photo-removable nitroveratryl groups which partially mask the highly polar alendronate HMBP scaffold. Photo-responsive prodrugs of alendronate are stable in physiological conditions and display reduced toxicity compared to alendronate against MDA-MB-231 cancer cells. However, the antiproliferative effect of these prodrugs is efficiently restored after cleavage of their nitroveratryl groups upon exposure to UV light. In addition, substitution of alendronate with such photo-responsive substituents drastically reduces its bone-binding properties, thereby potentially improving its biodistribution in soft tissues after i.v. administration. The development of such lipophilic photo-responsive prodrugs is a promising approach to fully exploit the anticancer effect of HMBPs on non-skeletal tumors.

Impact of Bisphosphonate Therapy on Oral Health in Patients with Breast and Prostate Cancer and Bone Metastases: A Comprehensive Study.

This study investigates the impact of bisphosphonate therapy on the stomatognathic system in 80 patients with cancer of the breast and prostate with bone metastases. Bisphosphonates are integral for managing skeletal complications in these malignancies but are associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ), affecting 0.8-18.5% of patients. BRONJ manifests with pain, neuropathy, tissue swelling, mucosal ulceration, tooth mobility, and abscesses, yet its pathogenesis remains elusive, complicating risk prediction. The research employed comprehensive dental and radiological evaluations. Dental status was assessed using DMFT and OHI-S indices, Eichner's classification, and clinical periodontal measurements like the pocket depth (PD), clinical attachment loss (CAL), and modified Sulcus Bleeding Index (mSBI). A radiological analysis included panoramic X-rays for radiomorphometric measurements and TMJ lateral radiographs. Results indicated a significant decline in oral hygiene in patients with cancer after bisphosphonate therapy, marked by increased DMFT and OHI-S scores. Periodontal health also showed deterioration, with increased PD and CAL readings. The incidence of BRONJ symptoms was noted, although exact figures are not quantified in this abstract. The study also revealed changes in radiomorphometric parameters, suggesting bisphosphonates' impact on bone density and structure. No substantial alterations were observed in TMJ function, indicating a need for extended observation to understand bisphosphonates' long-term effects on the stomatognathic system. These findings highlight the importance of continuous dental monitoring and prophylaxis in patients undergoing bisphosphonate therapy. Implementing meticulous oral care protocols is essential for mitigating BRONJ risk and managing the complex oral health challenges in patients with cancer.

A Representative Clinical Course of Progression, with Molecular Insights, of Hormone Receptor-Positive, HER2-Negative Bone Metastatic Breast Cancer.

Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. Therefore, this review explores the clinical course of a representative patient with hormone receptor-positive bone metastatic breast cancer, examining key treatment options at each stage and their effects on preventing and treating bone metastases.

Influence of zoledronic acid and pamidronate on tooth eruption in children with osteogenesis imperfecta.

INTRODUCTION: Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is bisphosphonate therapy. Previous animal studies have shown that bisphosphonates delay tooth eruption. The aim of this study is to determine whether patients with OI treated with pamidronate and/or zoledronic acid have a delayed eruption age compared to a control group of healthy children. METHODS: An ambispective longitudinal cohort study evaluating the age of eruption of the first stage mixed dentition in a group of children with OI (n = 37) all treated with intravenous bisphosphonates compared with a group of healthy children (n = 89). Within the study group, the correlation (Pearson correlation test) between the type of medication administered (pamidronate and/or zoledronic acid) and the chronology of tooth eruption is established, as well as the relationship between the amount of cumulative dose received and tooth eruption. RESULTS: The age of eruption of the study group was significantly delayed compared to the age of eruption of the control group for molars and lateral incisors (p < 0.05). Patients who received higher cumulative doses had a delayed eruption age compared to those with lower cumulative doses (p < 0.05). There is a high positive correlation between age of delayed tooth eruption and Zoledronic acid administration. CONCLUSION: Patients with OI have a delayed eruption of the 1st stage mixed dentition compared to a control group of healthy children. This delayed eruption is directly related to the cumulative dose of bisphosphonates and the administration of zoledronic ac.