The effect of black cohosh extract and risedronate coadministration on bone health in an ovariectomized rat model.

Preparations of black cohosh extract are sold as dietary supplements marketed to relieve the vasomotor symptoms of menopause, and some studies suggest it may protect against postmenopausal bone loss. Postmenopausal women are also frequently prescribed bisphosphonates, such as risedronate, to prevent osteoporotic bone loss. However, the pharmacodynamic interactions between these compounds when taken together is not known. To investigate possible interactions, 6-month-old, female Sprague-Dawley rats underwent bilateral ovariectomy or sham surgery and were treated for 24 weeks with either vehicle, ethinyl estradiol, risedronate, black cohosh extract or coadministration of risedronate and black cohosh extract, at low or high doses. Bone mineral density (BMD) of the femur, tibia, and lumbar vertebrae was then measured by dual-energy X-ray absorptiometry (DEXA) at weeks 0, 8, 16, and 24. A high dose of risedronate significantly increased BMD of the femur and vertebrae, while black cohosh extract had no significant effect on BMD individually and minimal effects upon coadministration with risedronate. Under these experimental conditions, black cohosh extract alone had no effect on BMD, nor did it negatively impact the BMD-enhancing properties of risedronate.

Evaluating calcium channel blockers and bisphosphonates as otoprotective agents in cochlear implantation hearing preservation candidates.

OBJECTIVES: Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. METHODS: Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500 Hz ≤80 dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. RESULTS: Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22-4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3-6 months later (OR = 0.40, 95% CI = 0.04-4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00-1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. DISCUSSION: There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. CONCLUSION: Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.

Osteonecrosis of the Jaw Associated with Bisphosphonates Infusion for Treatment of Plasma Cell Myeloma-A Retrospective Observational Study of Northern Portuguese Population.

Objectives: To verify medication-related osteonecrosis of the jaw (MRONJ) frequency among patients with plasma cell myeloma (PCM) that had been treated with bisphosphonates, to identify predisposing factors that could influence the development of osteonecrosis. Methods: This observational retrospective study was performed at the Department of Hematology of Hospital Center of Porto (CHUP), Portugal. Results: The study population (n = 112) had a 15.2% (n = 17) prevalence of osteonecrosis. Clinically, bone exposure was the most frequently observed sign, present in 100% (n = 17) of the patients, followed by inflammation in 82.4% (n = 14), orofacial pain in 70.6% (n = 12), suppuration in 47.1% (n = 8), and intra or extra-oral fistula in 17.6% (n = 3) of the cases. The most frequent triggering local factor was dental extraction (82.4%). There was a dependence between the presence of extractions and the development of MRONJ (p < 0.001) but not with the time elapsed from the initiation of infusions with BPs and dental extractions (p = 0.499). In the sample of patients with multiple myeloma (MM), 13.8% were found to be more likely to develop MRONJ after an extraction. Conclusions: The most common local predisposing factor was dental extraction. No dependence was observed between the development of osteonecrosis and the time elapsed from the beginning of treatment with bisphosphonates infusions to surgical procedures.

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.

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 (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) 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.

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.

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.

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.

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.

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.

S-Allylmercapto-N-Acetylcysteine (ASSNAC) Attenuates Osteoporosis in Ovariectomized (OVX) Mice.

Osteoporosis is a bone-debilitating disease, demonstrating a higher prevalence in post-menopausal women due to estrogen deprivation. One of the main mechanisms underlying menopause-related bone loss is oxidative stress. S-allylmercapto-N-acetylcysteine (ASSNAC) is a nuclear factor erythroid 2-related factor 2 (Nrf2) activator and cysteine supplier, previously shown to have anti-oxidation protective effects in cultured cells and animal models. Here, we studied the therapeutic potential of ASSNAC with and without Alendronate in ovariectomized (OVX) female mice. The experimental outcome included (i) femur and L3 lumbar vertebra morphometry via Micro-Computed Tomography (µCT); (ii) bone remodeling (formation vs. resorption); and (iii) oxidative stress markers in bone marrow (BM) cells. Four weeks after OVX, there was a significant bone loss that remained evident after 8 weeks, as demonstrated via µCT in the femur (cortical and trabecular bone compartments) and vertebra (trabecular bone). ASSNAC at a dose of 50 mg/Kg/day prevented bone loss after the four-week treatment but had no significant effect after 8 weeks, while ASSNAC at a dose of 20 mg/Kg/day significantly protected against bone loss after 8 weeks of treatment. Alendronate prevented ovariectomy-induced bone loss, and combining it with ASSNAC further augmented this effect. OVX mice demonstrated high serum levels of both C-terminal cross-linked telopeptides of type I collagen (CTX) (bone resorption) and procollagen I N-terminal propeptide (P1NP) (bone formation) after 2 weeks, and these returned to control levels after 8 weeks. Alendronate, ASSNAC and their combination decreased CTX and increased P1NP. Alendronate induced oxidative stress as reflected by decreased glutathione and increased malondialdehyde (MDA) levels, and combining it with ASSNAC partially attenuated these changes. These results portray the therapeutic potential of ASSNAC for the management of post-menopausal osteoporosis. Furthermore, ASSNAC ameliorates the Alendronate-associated oxidative stress, suggesting its potential to prevent Alendronate side effects as well as improve its bone-protective effect.

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.

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.

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.

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).

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.

Long-term effectiveness of zoledronic acid in patients with Paget's disease of bone - a retrospective cohort study.

PURPOSE: The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to examine the long-term effectiveness of zoledronate. METHODS: Retrospective cohort study included consecutive patients≥18 years with a diagnosis of PDB, followed in the Rabin Medical Center (RMC) Institute of Endocrinology from 1973 to 2023. The cohort comprised two groups: patients treated/not treated with zoledronic acid (ZOL/NZOL). The primary outcome was the percentage of patients who achieved a biochemical therapeutic response. RESULTS: Overall, 101 patients with PDB were included, 68 in the ZOL group and 33 in the NZOL group. The mean age was 65.2 ± 10.0 years, and 47% were female. Notably, 77% exhibited monostotic involvement, and only 3% had experienced fractures attributed to PDB. Mean ALP level at diagnosis was 160 ± 70.6 U/L. The median follow-up duration was 17 years since PDB diagnosis, comparable between the groups. Primary outcome was more prevalent in the ZOL compared to the NZOL group [42 patients (88%) VS 11 patients (52%) respectively, P = 0.004]. At the end of follow-up, mean ALP levels in the NZOL group were significantly higher than the levels in the ZOL group irrespective of the number of infusions received. CONCLUSION: The majority of patients with PDB experience a mild disease course, marked by monostotic involvement and a low prevalence of fractures. Zoledronic acid effectively manages PDB, providing sustained biochemical response. The necessity for multiple zoledronic acid injections remains questionable, often implemented due to osteoporosis.

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.