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To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn. Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% (± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support. Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers. • Twenty-one out of twenty-four interventional studies were conducted by a single institution. • Categories of interventions included: rehabilitative exercise programs, pharmacologic agents, and nutrition support. • Pediatric patients had extensive burns covering, on average, 44.3% (± 9.5) of the total body surface area. • In future research, it is important to evaluate the heterogeneity of intervention effects. • Also, whether an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers. [ABSTRACT FROM AUTHOR]

Case: We report a 15-year-old adolescent boy being followed up for 6 years with osteogenesis imperfecta (OI). Genetic testing of this child revealed a novel missense variant c.925C>T p.Arg309Cys in the CREB3L1 gene. Treatment with regular pamidronate therapy showed increased bone mineral density and a reduced fracture rate. His lower limb rush rodding improved his mobility. His withdrawal from bisphosphonate therapy worsened his mobility status but started improving after he restarted treatment, suggesting a response to pamidronate therapy. Conclusion: We report a novel biallelic missense variant c.925C>T, p.Arg309Cys, in the CREB3L1 gene causing OI, which responded to bisphosphonate therapy and corrective surgery. [ABSTRACT FROM AUTHOR]

Background: Legg-Calvé-Perthes disease (LCPD) presents in childhood with idiopathic avascular necrosis of the femoral head(s), which can lead to disability and the need for corrective surgery at an early age. Bisphosphonates are a group of drugs that prevent osteoclastic bone resorption and may be helpful in the treatment of LCPD. So far, no trial has been conducted to investigate the effect of monthly intravenous pamidronate in the treatment of LCPD in children. Therefore, we assessed this issue in this study. Materials and Methods: This study was conducted as a clinical trial on children with LCPD who were referred to Mofid Children's Hospital (Iran-Tehran) during 2022 and 2023. Pamidronate was injected monthly and intravenously at a dose of 1 mg/kg/dose. Both groups were the same in terms of the type of treatment received (except pamidronate), the number of visits, and other follow-up parameters. The study was conducted for one year. The significance level was considered less than 0.05. Results: Forty-seven patients were included in the study. Twenty-one (60%) were in the pamidronate group, and 26 (40%) were in the control group. The mean age in the intervention group was 6.19 ± 1.69 years, and it was 6.15 ± 1.85 years in the control group (P-value=0.944). There was no statistically significant difference in children's gender (P-value = 0.731). Patients with pamidronate had a better overall score than the control group. The overall score in the pamidronate group was 2.37 more than the control group, but this difference was not statistically significant (P value=0.753). The scores of pain, lameness, walking, distance, squat, cross leg, and range of motion (ROM) in the pamidronate group were not significantly different from the control group (P value>0.05). Conclusion: Pamidronate can improve the clinical results of children with Legg-Calve-Perthes disease, and it is recommended that this drug be used along with the usual treatments for these patients. [ABSTRACT FROM AUTHOR]

Background: Legg-Calvé-Perthes disease (LCPD) presents in childhood with idiopathic avascular necrosis of the femoral head(s), which can lead to disability and the need for corrective surgery at an early age. Bisphosphonates are a group of drugs that prevent osteoclastic bone resorption and may be helpful in the treatment of LCPD. So far, no trial has been conducted to investigate the effect of monthly intravenous pamidronate in the treatment of LCPD in children. Therefore, we assessed this issue in this study. Materials and Methods: This study was conducted as a clinical trial on children with LCPD who were referred to Mofid Children's Hospital (Iran-Tehran) during 2022 and 2023. Pamidronate was injected monthly and intravenously at a dose of 1 mg/kg/dose. Both groups were the same in terms of the type of treatment received (except pamidronate), the number of visits, and other follow-up parameters. The study was conducted for one year. The significance level was considered less than 0.05. Results: Forty-seven patients were included in the study. Twenty-one (60%) were in the pamidronate group, and 26 (40%) were in the control group. The mean age in the intervention group was 6.19 ± 1.69 years, and it was 6.15 ± 1.85 years in the control group (P-value=0.944). There was no statistically significant difference in children's gender (P-value = 0.731). Patients with pamidronate had a better overall score than the control group. The overall score in the pamidronate group was 2.37 more than the control group, but this difference was not statistically significant (P value=0.753). The scores of pain, lameness, walking, distance, squat, cross leg, and range of motion (ROM) in the pamidronate group were not significantly different from the control group (P value>0.05). Conclusion: Pamidronate can improve the clinical results of children with Legg-Calve-Perthes disease, and it is recommended that this drug be used along with the usual treatments for these patients.

Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid (ZA) in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which ZA was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of ZA, the second case experienced hypocalcemia requiring calcium treatment after ZA infusion. Our report shows that ZA may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of ZA in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients.

Abstract Background Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. Case presentation An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner’s request because of worsened hypocalcemia and renal failure. Conclusions Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient’s underlying conditions. Therefore, the patient’s condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of patients with calcification defense. Methods PubMed, Embase databases, CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense. Then, the relevant information of patients was extracted for statistical analysis. Results A total of 18 case reports were selected involving 20 patients. Thirteen patients (65.0%) were treated with pamidronate, four (20.0%) were treated with etidronate, two (10.0%) were treated with alendronate, and one (5.0%) was treated with zoledronic acid. Thirteen patients (65.0%) recovered completely, the recovery time of whom ranged from half month to nine months. The tolerance of bisphosphonates in most patients(90.0%)was good, while one patient who did not tolerate pamidronate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage. Conclusions Bisphosphonates, an inhibitor of bone resorption, is effective and safe in the treatment of patients with calcification defense.

Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid (ZA) in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which ZA was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of ZA, the second case experienced hypocalcemia requiring calcium treatment after ZA infusion. Our report shows that ZA may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of ZA in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients. [ABSTRACT FROM AUTHOR]

Background: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. Case presentation: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. Conclusions: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate. [ABSTRACT FROM AUTHOR]

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.

Purpose Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. Methods We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. Results The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. Conclusions Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

Purpose: Bisphosphonate (BP) medications can be applied to prohibit the damage of bone density and the remedy of bone illnesses such as osteoporosis. As the metal chelating of phosphonate groups are nearby large with six O atoms possessing the high negative charge, these compounds are active toward producing the chelated complexes through drug design method. BP agents have attracted much attention for the clinical treatment of some skeletal diseases depicted by enhancing of osteoclast-mediated bone resorption. Design/methodology/approach: In this work, it has been accomplished the CAM-B3LYP/6–311+G(d, p)/LANL2DZ to estimate the susceptibility of SWCNT for adsorbing alendronate, ibandronate, neridronate and pamidronate chelated to two metal cations of 2Mg2+, 2Ca2+, 2Sr2+ through nuclear magnetic resonance and thermodynamic parameters. Therefore, the data has explained that the feasibility of using SWCNT and BP agents becomes the norm in metal chelating of drug delivery system which has been selected through alendronate → 2X, ibandronate → 2X, neridronate → 2X and pamidronate → 2X (X = Mg2+/Ca2+/Sr2+) complexes. Findings: The thermodynamic results have exhibited that the substitution of 2Ca2+ cation by 2Sr2+ cation in the structure of bioactive glasses can be efficient for treating vertebral complex fractures. However, it has been observed the most fluctuation in the Gibbs free energy for BPs → 2Sr2+ at 300 K. Furthermore, Monte Carlo simulation has resulted by increasing the dielectric constant in the aqueous medium can enhance the stability and efficiency of BP drugs for preventing the loss of bone density and treating the osteoporosis. Originality/value: According to this research, by incorporation of chelated 2Mg2+, 2Ca2+ and 2Sr2+ cations to BP drugs adsorbed onto (5, 5) armchair SWCNT, the network compaction would increase owing to the larger atomic radius of Sr2+ cation rather than Ca2+ and Mg2+, respectively. [ABSTRACT FROM AUTHOR]

Osteoporosis in childhood distinguishes itself from adulthood in four important ways: 1) challenges in distinguishing otherwise healthy children who have experienced fractures due to non-accidental injury or misfortunate during sports and play from those with an underlying bone fragility condition; 2) a preponderance of monogenic "early onset" osteoporotic conditions that unveil themselves during the pediatric years; 3) the unique potential, in those with residual growth and transient bone health threats, to reclaim bone density, structure, and strength without bone-targeted therapy; and 4) the need to benchmark bone health metrics to constantly evolving "normal targets", given the changes in bone size, shape, and metabolism that take place from birth through late adolescence. On this background, the pediatric osteoporosis field has evolved considerably over the last few decades, giving rise to a deeper understanding of the discrete genes implicated in childhood-onset osteoporosis, the natural history of bone fragility in the chronic illness setting and associated risk factors, effective diagnostic and monitoring pathways in different disease contexts, the importance of timely identification of candidates for osteoporosis treatment, and the benefits of early (during growth) rather than late (postepiphyseal fusion) treatment. While there has been considerable progress, a number of unmet needs remain, the most urgent of which is to move beyond the monotherapeutic anti-resorptive landscape to the study and application of anabolic agents that are anticipated to not only improve bone mineral density but also increase long bone cross-sectional diameter (periosteal circumference). The purpose of this review is to provide a practical guide to the diagnosis and management of osteoporosis in children presenting to the clinic with fragility fractures, one that serves as a step-by-step "how to" reference for clinicians in their routine clinical journey. The article also provides a sightline to the future, emphasizing the clinical scenarios with the most urgent need for an expanded toolbox of effective osteoporosis agents in childhood. [ABSTRACT FROM AUTHOR]

Objective: We conducted this paper to decipher the efficacy of the combined chemotherapy of zoledronic acid and pamidronate in treating bone metastases from nonsmall cell lung cancer (NSCLC) and the effects on pain stress and bone metabolic indices. Methods: Patients with bone metastases from NSCLC were allocated into Group A and Group B. Patients in the Group A were administrated with pamidronate combined chemotherapy and patients in the Group B were administrated with zoledronic acid combined chemotherapy. The efficacy, pain symptom scores, quality of life scores, serum inflammatory factor, serum bone metabolic indices, serum pain stress indicators, and the occurrence of adverse effects were compared in patients of the two groups. Results: The total effective rate of treatment was higher in the Group B than in the Group A. After treatment, reduced Numerical Rating Scale scores and elevated Karnofsky Performance Score score, reduced serum levels of N‐terminal mid‐fragment of osteocalcin, N‐terminal propeptide of type I procollagen, bone‐specific alkaline phosphatase, and type I collagen hydroxyl terminal peptide β special sequence, reduced serum levels of C‐reactive protein, procalcitonin, tumor necrosis factor‐α, and interleukin‐6, as well as decreased levels of bradykinin, substance P, neuropeptide Y, and β‐endorphin were found in the Group B versus the Group A. No notable difference was witnessed in the rate of adverse reactions between the Group A and the Group B. Conclusion: Zoledronic acid combined with chemotherapy can effectively treat bone metastases of NSCLC and improve pain stress and bone metabolic status, which has value that can be promoted and applied in clinical treatment. [ABSTRACT FROM AUTHOR]

The present study outlines the fabrication and characterization of pamidronate (PDS) embedded nanofibrous scaffolds based on polycaprolactone/polycaprolactone-polyethyleneglycol-polycaprolactone (PCL/CEC) blends for osteoporotic bone defect management. The electrospinning technique has been utilized to fabricate PDS-loaded scaffolds and the effect of PDS on blends was evaluated by analyzing the surface morphology, wettability, biodegradability, and in vitro cytocompatibility. In vitro studies using human osteosarcoma cell lines (hOS) showed the non-cytotoxic nature of the scaffolds. The fibroporous architecture of PCL/CEC-PDS scaffolds along with their appropriate mechanical properties and ability to support cell growth in vitro suggests their potential for osteoporotic bone defect management. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women and most often metastasizes to the bone, resulting in skeletal-related events (SREs). Bone-modifying agents (BMAs) including denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b ligand (RANKL), and pamidronate, a bisphosphonate, are used to prevent these adverse events. To analyze the efficacy of denosumab versus pamidronate, we used the TriNetX research platform and compared the outcomes of pathologic fracture, spinal cord compression, and overall 5-year survival rate between each pharmacotherapy. There was no statistical difference for an increased risk in pathological fractures (2.7% vs. 2.8%, P = 0.88), spinal cord compression (2.6% vs. 2.7%, P = 0.88), or 5-year survival rate (45.5% vs. 52.4%, P = 0.78) for the denosumab cohort versus the pamidronate cohort. Since neither therapy showed an increased risk in the adverse effects measured in this study, factors such as patient preference, financial costs, and additional side effects of each medication should be taken into consideration when choosing a therapy for bone metastases in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Chronic recurrent multifocal osteomyelitis (CRMO) is the most common autoinflammatory disease of the bone characterized by pain and inflammatory lesions without an infectious agent. The aim of this study is to evaluate the clinical, laboratory, and imaging features and treatments of paediatric patients with CRMO followed in our pediatric rheumatology clinic. Material and Methods: Medical records of ten patients diagnosed with CRMO according to Bristol diagnostic criteria between January 2018 and June 2021 were retrospectively reviewed. Results: The mean age at diagnosis was 9.3 years, and eight of the patients were male. One patient had concomitant psoriasis, two patients had familial Mediterranean fever and one patient had a history of immunoglobulin A vasculitis. Half of the patients had a moderate acute phase reactant elevation. The most frequently involved bones were the lower extremity bones. While localized magnetic resonance imaging (MRI) was the most commonly used imaging modality in the diagnosis of CRMO, silent bone lesions (15%) were detected only by the whole-body MRI. Non-steroidal anti-inflammatory drug (NSAID) was given to all patients. As second-line therapy, methotrexate and pamidronate were employed on seven and five patients respectively. Three of the patients received anti-TNF treatment (etanercept and infliximab) as the third-line therapy. Imaging with whole-body MRI is important due to clinically silent bone lesions, especially in the course of CRMO. Conclusion: Concomitant familial Mediterranean fever was not rare in cases with CRMO and treatment of CRMO might be challenging due to the need for anti-TNF treatment in a considerable number of patients. [ABSTRACT FROM AUTHOR]

Objective: Pamidronate is one of the main therapies for Fibrous Dysplasia (FD), with documented enhancements in patients' clinical characteristics. Nevertheless, its usage has yielded inconclusive results. Therefore, this review aimed to investigate pamidronate's impact on several clinical and biochemical outcomes in FD patients. Materials and Methods: This review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, ProQuest, Wiley, and EBSCO search databases were used to search the literature. Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) was applied for quality assessment of the included studies and Review Manager (RevMan) 5.4 was employed in performing the meta-analysis. Results: There are eight and seven studies used in the meta-analysis and systematic review, respectively. The results showed there are two studies with a low risk of bias and six with a moderate category. All papers included in this meta-analysis showed significant differences in the reduction of bone pain (p<0.00001) and serum alkaline phosphatase (SAP) (p=0.04) after pamidronate treatment compared to the before-treatment groups. Conclusion: The findings of this study indicated that pamidronate therapy had been proven to significantly reduce bone pain and increase SAP in FD patients. However, trials with more age-specific samples and a lower risk of bias should be carried out to determine the statistical significance of overall results. [ABSTRACT FROM AUTHOR]

Approximately 70% of multiple myeloma patients develop pathologic fractures. Osteoclast inhibitors can provide reduction in vertebral fractures with an increased risk of osteonecrosis of the jaw (ONJ). ONJ associated with currently used osteoclast inhibitors causes significant morbidity, often from delayed diagnosis and ineffective treatment. The TriNetX Diamond Network was used to create patient cohorts for each medication: alendronate, pamidronate, zoledronic acid, and denosumab. All patients had a diagnosis of multiple myeloma as identified by International Classification of Disease–10 (ICD-10) code C90.0. Pamidronate, zoledronic acid, and denosumab were each compared to alendronate for 5-year incidence of pathologic vertebral fracture (ICD-10 M48.50XA) and development of ONJ. The 5-year risk of pathologic vertebral fracture was not statistically different between alendronate versus pamidronate, zoledronic acid, and denosumab. However, the 5-year risk of ONJ was significantly higher for both zoledronic acid and denosumab (relative risk 4.85 and 2.9, respectively). This study shows that fracture reduction risk is comparable for all four treatments in multiple myeloma patients, but ONJ risk is lowest for alendronate and pamidronate. Overall, these data support the continued use of pamidronate and alendronate in multiple myeloma patients. [ABSTRACT FROM AUTHOR]

Objective: Pamidronate is one of the main therapies for Fibrous Dysplasia (FD), with documented enhancements in patients' clinical characteristics. Nevertheless, its usage has yielded inconclusive results. Therefore, this review aimed to investigate pamidronate’s impact on several clinical and biochemical outcomes in FD patients. Materials and Methods: This review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, ProQuest, Wiley, and EBSCO search databases were used to search the literature. Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) was applied for quality assessment of the included studies and Review Manager (RevMan) 5.4 was employed in performing the meta-analysis. Results: There are eight and seven studies used in the meta-analysis and systematic review, respectively. The results showed there are two studies with a low risk of bias and six with a moderate category. All papers included in this meta-analysis showed significant differences in the reduction of bone pain (p

BACKGROUND: The pulsed electromagnetic fields (PEMFs) seem effective in increasing bone mineral density and promoting osteogenesis and bone healing. OBJECTIVE: To examine the effect of two different modalities of PEMFs therapy in comparison with the recommended pharmacological treatment on experimental osteoporosis in rats. METHODS: The experimental model of estrogen-deficient osteoporosis induced by ovariectomy was used in this study. The animals were exposed to PEMFs of various frequencies (40 Hz and 25 Hzk), intensities (10 mT and 36.4 μ T), lengths of exposure, and the effects were compared with the standard treatment with pamidronate, vitamin D, and calcium supplementation. RESULTS: The application of PEMF 40Hz , significantly reduced the osteoporotic bone loss in female rats that were confirmed with biochemical, biomechanical, and histological analyses. These effects were more pronounced than in osteoporotic animals treated with pamidronate, vitamin D, and calcium supplementation. On the contrary, the exposure to PEMF 25Hz did not show restorative effects but led to further progression of osteoporosis. CONCLUSION: The exposure to PEMF 40Hz , significantly restored osteoporosis and attenuated bone fragility in comparison to the rats exposed to PEMF 25Hz or those treated with pamidronate, vitamin D, and calcium supplementation. [ABSTRACT FROM AUTHOR]

Bisphosphonate (BP) agents have attracted much attention for their precise therapy in some skeletal maladies demonstrated by enhancing osteoclast-mediated bone resorption. In this work, the use of CAM-B3LYP/6-311+G(d,p)/LANL2DZ to estimate the susceptibility of single-walled carbon nanotube (SWCNT) for adsorbing alendronate, ibandronate, neridronate, and pamidronate chelated to two metal cations of 2Mg2+, 2Ca2+, and 2Sr2+ through nuclear magnetic resonance and thermodynamic parameters has been accomplished. For most biological medications, oral bioavailability is too low to reach a therapeutic level, and advanced delivery systems such as formulations including permeation enhancers or enzyme inhibitors, lipid-based nanocarriers, and microneedles will likely increase the oral bioavailability of these medications properly. Therefore, the measurements have described that the eventuality of using SWCNT and BP agents becomes the norm in metal chelating of the drug delivery system, which has been selected through (alendronate, ibandronate, neridronate, pamidronate) → 2X (X = Mg2+/Ca2+/Sr2+) complexes. The NMR results of chelated alendronate, ibandronate, neridronate, and pamidronate complexes adsorbed onto (5,5) armchair SWCNT have remarked the location of active sites of tagged nitrogen (N), phosphorus (S), oxygen (O), and metal cations of magnesium (Mg2+), calcium (Ca2+), and strontium (Sr2+) in these molecules which replace the movement of the charge electron transfer in polar bisphosphonates (BPs) toward (5,5) armchair carbon nanotube (CNT). The thermodynamic results have exhibited that the substitution of 2Ca2+ cation by 2Sr2+ cation in the compound of the bioactive glasses can be efficient for treating vertebral complex fractures. However, the most fluctuation in the Gibbs free energy for BPs → 2Sr2+ has been observed at 300 K. This manuscript aimed to show that (5,5) armchair SWCNT can easily penetrate in the bone cells, delivering chelated BP–cations directly to the bone tissue. Drug delivery systems can improve the pharmacological profile, therapeutic profile, and efficacy of BP drugs and lower the occurrence of off-targets. [ABSTRACT FROM AUTHOR]

Secondary chronic osteomyelitis (SCO) is caused by bacterial infection leading to progressive jawbone destruction. Antibiotics are used as first-line treatment; surgical therapy is usually extensive and may not provide a cure. Bisphosphonates have been reported to be successful in patients with primary nonbacterial osteomyelitis, and literature indicates promising results in SCO. A 38-year-old patient presented with a progressive mandible-destruction 17 years after wisdom tooth extraction. Several treatment attempts have been unsuccessful. Seeking a second opinion, the patient was then interdisciplinary treated with 90 mg of intravenous pamidronate every four weeks, three times. The patient did not experience side effects presenting a considerable improvement in mouth opening and reporting a dissolvent of signs of pain or infection. The MRI showed edema reduction and decreased contrast uptake. Therefore, bisphosphonate treatment of secondary chronic osteomyelitis of the jaw is a safe and effective option in selected cases after unsuccessful first- and second-line therapy. [ABSTRACT FROM AUTHOR]

Multiple myeloma frequently leads to bone complications characterized by the presence of lytic defects with high incidence of pathologic fractures, hypercalcemia and osteoporosis. The basic cause of this effect lies in the ability of malignant plasmatic cells to stimulate osteoclasts which are cells participating in the process of resorption of osseous tissue. Increased resorption of osseous matrix by means of osteoclasts activation runs concurrently with the process of decrease of activity of osteoblasts which are cells synthesizing osseous matrix of the bones. It has been a long time since the efforts to cope with consequences of unfavorable influence of myeloma cells on osseous tissue has been under way mainly by symptomatic means: local radiotherapy, surgical reconstruction of the bone, especially in cases of vertebral involvement, and anesthesia. Recently new weapon has been added to the arsenal for treatment of bone complications: bisphosphonates which are agents inhibiting the activity of osteoclasts and thus promoting the consolidation of the bones. Results of controlled clinical trials showed that such a medications as clodronate, pamidronate and zoledronate considerably decrease the incidence of bone complications in patients with multiple myelomas. Pamidronate and xoledronate turned out to be more active, at the same time long term usage of zoledronic acid can lead to development of such an adverse complication as osteonecrosis of jaw. The ASCO recommendations indicates the appropriateness of long term use of pamidronate or zoledronate in patients with multiple myelomas and bone complications.

Background Osteopenia and osteoporosis represent a prominent cause of morbidity in children with thalassemia. Multiple factors are responsible for the pathogenesis of bone loss in thalassemia, including diabetes, hypothyroidism, parathyroid gland dysfunction, accelerated hemopoiesis, direct iron toxicity of osteoblasts, iron chelators, and deficiencies of growth hormone or insulin growth factors. Purpose To assess the effect of pamidronate administration on β-thalassemia major-induced osteoporosis in children. Methods This study assessed the effects of different treatments (calcium and vitamin D versus calcium, vitamin D, and pamidronate) on patients with β-thalassemia major and osteoporosis. Bone mineral density (BMD) and z scores were measured at baseline and after 1 year of treatment using dual-energy x-ray absorptiometry. Results The mean baseline BMD values of the lumbar spine were 0.71±0.07 (g/cm2) and 0.74±0.07 (g/cm2), respectively, while those at the end of the study were 0.81±0.07 (g/cm2) (P0.05), respectively. The mean baseline z scores of the lumbar spine were -3.53±0.55 and -3.17±0.61, while those after treatment were -2.1±0.32 (P=0.001) and -3.11±0.67 (P>0.05), respectively. The baseline alkaline phosphatase levels were 351.5±86.07 μg/dL and 357.6±89.7 μg/dL, while those after treatment were 220.4± 59.26.07 μg/dL (P0.05), respectively. Conclusion Pamidronate administration effectively increased the BMD and z scores of children with β-thalassemia major. Pamidronate had a favorable safety profile with no related serious adverse events during the study period.

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G–tagged pamidronate complex–loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37 nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory disorder resulting from the multifocal bone and bone marrow lesions with periodic relapses and remissions and with an uncertain prognosis. Treatment options in CRMO are based on expert opinion and relatively small groups of patients. A nine-year-old female patient with no significant past medical history presented with compression fractures and multifocal bone lesions in the thoracic and lumbar spine, as shown in imaging (CT, MRI). Densitometry revealed a diffuse decrease in bone density. Based on the patient's clinical image and above examinations, the other possible aetiologies—infectious (including tuberculosis), neoplasms, Langerhans cell histiocytosis—were ruled out, which led to eventual final diagnosis—CRMO. The patient was successfully treated with pamidronate infusion initiated in cycles over three consecutive days every 3 months. In addition to clinical improvement, there was a significant remission of inflammation and bone structure healing assessed by MRI after four treatment cycles. Intravenous bisphosphonates usage seems to be a good therapeutic option in CRMO paediatric patients with spinal localization of the lesions complicated by compressive fractures. However, more data, based on larger patient populations, are needed to provide a detailed paediatric CRMO treatment algorithm. [ABSTRACT FROM AUTHOR]

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P

Huali Gu,1 Yizhuo Wang,1 Dongsheng Huang,1 Xunda Ji,2 Yi Zhang,1 Jianmin Ma,3 Mei Li,4 Weiling Zhang,1 Huimin Hu,1 Jing Li,1 Pinwei Zhang1 1Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Ophthalmic Oncology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Dongsheng Huang, Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, West South Road 2, Yizhuang Economic and Technological Development Zone, Daxing District, Beijing, 100176, People’s Republic of China, Tel +86 01058266032, Email hds5180@sina.com Xunda Ji, Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Kong Jiang Road 1665, Shanghai, 200092, People’s Republic of China, Tel +86 15921670980, Email jixunda@xinhuamed.com.cnPurpose: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. This study evaluated the clinical and imaging features, treatment, and prognosis of patients with recurrent RB with limb bone metastases and without central nervous system involvement.Patients and Methods: The clinical data of five patients with RB with limb bone metastases who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between January 2015 and January 2021 were analyzed retrospectively.Results: Three males and two females were included (seven eyes: four group E and one each of group D, C, and B). The most common symptom was pain. Three patients had bone marrow and lymph node metastases. Three patients had single and two had multiple skeletal lesions. The main bones that were involved were the femur, humerus, talus, and ulna. The simultaneous involvement of the bone marrow and cortex was also observed. Serum neuron-specific enolase (NSE) levels were significantly elevated in four cases and slightly elevated in one case; primary intravenous chemotherapy resulted in a decrease in NSE levels and the gradual resolution of the bone lesions. Two patients died at the time of follow-up and three were in complete remission. The results of the statistical analysis showed that anterior chamber invasion was correlated with prognosis, and there was significant difference in the decrease in the serum NSE levels after intravenous chemotherapy.Conclusion: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases earlier. Anterior chamber invasion may be a risk factor. The simultaneous involvement of the bone marrow and cortex is characteristic manifestations in images of RB with bone metastases. Multidisciplinary treatment especially intravenous chemotherapy is useful, at least at the beginning.Keywords: recurrent, NSE, SRE, pathological fracture, pamidronate, osteoclast inhibitors

Objectives: The objectives were to assess changes in radiological disease activity in children with chronic non-bacterial osteomyelitis (CNO) receiving pamidronate therapy and to test a modified radiological index for non-bacterial osteitis (mRINBO) in CNO. mRINBO was used for standardized reporting and quantification of whole-body MRI (WBMRI) findings resulting in an individual summary patient score. Methods: WBMRI was retrospectively assessed in 18 children with CNO at baseline and after receiving pamidronate therapy for one year. Parameters of interest were: number and anatomic site of radiologically active bone lesions (RAL), size of RAL, extramedullary affection, spinal involvement and changes in mRINBO, which includes both the number and maximal size of RAL (RALmax) in addition to extramedullary and chronic changes. Results: At the time of diagnosis, the mean age of the children was 9.8 (sd, 8.7–10.9) years and 11/18 were females. The number of RALs per patient decreased from median [interquartile range] 4.5 [3–8] to 3 [2–5] RALs per patient (p = 0.02) and extramedullary inflammatory changes regressed. Sixty-one percent of all RALs occurring at baseline resolved and three children became without active inflammatory lesions by WBMRI. The median size of RALs did not change when taking new lesions occurring in 7/18 children into account, but RALmax decreased significantly from 39 [29–45] mm at baseline to 28 [20–40] mm (p < 0.01) at year-one with a concomitant decrease of mRINBO from a median of 5 [4–7] to 4 [3–5] (p = 0.05). Conclusions: Pamidronate therapy resulted in a decrease of mRINBO from baseline to year one. mRINBO may be a potential scoring method to quantify changes in radiological disease activity in children with CNO. However, further studies are needed to test feasibility and validity of mRINBO. [ABSTRACT FROM AUTHOR]

Purpose Osteogenesis imperfecta (OI) is a rare bone fragility disorder caused by defects in type 1 collagen biosynthesis. This study investigated the genotype-phenotype correlations and the efficacy of pamidronate therapy in patients with OI in a single academic center. Methods This study included 24 patients with OI. A clinical scoring system was used to evaluate disorder severity. COL1A1 and COL1A2 genes were analyzed in 13 patients using Sanger sequencing. Genotype-phenotype correlations and the efficacy of pamidronate therapy were analyzed through a retrospective medical chart review. Results Of the 24 patients, 18 (75%) were classified as type I (12 with type Ia and 6 with type Ib), 2 as type III (8.4%), and 4 as type IV (16.7%). Type Ia patients showed relatively higher lumbar bone mineral density (BMD) standard deviation scores (SDS) and lower clinical scores than those with other types. Seven patients with qualitative mutations had lower lumbar BMD-SDS (P=0.015) and higher clinical scores (P=0.008) than 6 patients with quantitative mutations. The annual fracture frequency and lumbar BMD-SDS improved in patients with qualitative mutations after pamidronate treatment. Conclusions This study demonstrated that OI patients with qualitative mutations in COL1A1/2 had a more severe phenotype than those with quantitative mutations. Patients with qualitative mutations showed a significant reduction in fracture frequency and an increase in lumbar BMD-SDS after pamidronate treatment. Clinical score and genotype might be helpful for predicting phenotype and response to pamidronate therapy in OI patients.

Abstract The aim of this review was to describe orbital inflammation secondary to aminobisphosphonates by analyzing demographic data, clinical presentation, and treatment of the disease. This is a narrative literature review. The search was performed using databases such as Ovid/MEDLINE and COCHRANE. The searches were limited to papers in the English language. We found 43 cases of orbital inflammation due to aminobisphosphonates. Zoledronate was the drug most associated with orbital side effects. Clinical presentation was evident by unilateral involvement (89%), palpebral edema (88%), conjunctival congestion (81%), chemosis (79%), ocular pain (77%), ocular motility impairment (65%), proptosis (56%), and blurred vision (39%). It can affect both eyes (11%) and is accompanied by anterior uveitis (23%). Orbital inflammation secondary to aminobisphosphonates is a severe side effect. Clinically, it cannot be distinguished from idiopathic inflammation of the orbit. Therefore, it is important to rule out previous drug exposure. Timely treatment is vital to expect a favorable outcome, with systemic corticosteroids being the treatment of choice.

ObjectiveThe aim of this study was to investigate the relationship between type of antiresorptive medication and medication-related osteonecrosis of the jaw (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the prevention of MRONJ.Study designOur database of patients with MRONJ was reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3 frequent medication types associated with MRONJ. To evaluate the role of PMDE in the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center during a 10-year period were subclassified into 2 groups. Group I comprised patients seen for PMDE before the commencement of A/A and group II patients seen after prior exposure to antiresorptive and/or antiangiogenic medications. Fischer's exact test was used to compare the incidence of MRONJ in both groups.ResultsPatients on denosumab developed MRONJ earlier compared with zoledronate and pamidronate (P = .003). Group I had a significantly reduced incidence of MRONJ (0.9%) compared with group II (10.5%) (P

Abstract Osteogenesis imperfecta (OI) is a rare genetic heterogeneous disorder that causes increased bone fragility and recurrent fractures. For infants with OI and diffuse fractures, pain management, which is nuanced and specific for this population, is of the utmost importance to their neonatal care. Through experience at our center, we have developed a standard approach that has been successful in optimizing survival for these infants during this tenuous period. In this paper, we outline our multidisciplinary approach to pain management for infants with moderate to severe OI during the neonatal period, with emphasis on promotion of fracture healing and adequate pain control.

Background: Osteopenia and osteoporosis represent a prominent cause of morbidity in children with thalassemia. Multiple factors are responsible for the pathogenesis of bone loss in thalassemia, including diabetes, hypothyroidism, parathyroid gland dysfunction, accelerated hemopoiesis, direct iron toxicity of osteoblasts, iron chelators, and deficiencies of growth hormone or insulin growth factors. Purpose: To assess the effect of pamidronate administration on β-thalassemia major-induced osteoporosis in children. Methods: This study assessed the effects of different treatments (calcium and vitamin D versus calcium, vitamin D, and pamidronate) on patients with β-thalassemia major and osteoporosis. Bone mineral density (BMD) and z scores were measured at baseline and after 1 year of treatment using dualenergy x-ray absorptiometry. Results: The mean baseline BMD values of the lumbar spine were 0.71±0.07 (g/cm²) and 0.74±0.07 (g/cm²), respectively, while those at the end of the study were 0.81±0.07 (g/cm²) (P<0.001) and 0.78±0.07 (g/cm²) (P>0.05), respectively. The mean baseline z scores of the lumbar spine were -3.53±0.55 and -3.17±0.61, while those after treatment were -2.1±0.32 (P=0.001) and -3.11±0.67 (P>0.05), respectively. The baseline alkaline phosphatase levels were 351.5±86.07 μg/dL and 357.6±89.7 μg/dL, while those after treatment were 220.4± 59.26.07 μg/dL (P<0.001) and 320.3±83.99 μg/dL (P>0.05), respectively. Conclusion: Pamidronate administration effectively increased the BMD and z scores of children with β-thalassemia major. Pamidronate had a favorable safety profile with no related serious adverse events during the study period. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypercalcemia of malignancy is a metabolic complication of cancer that is potentially life-threatening. Intravenous (IV) bisphosphonates are first-line agents for the treatment of hypercalcemia of malignancy, but studies that examine their use in patients with renal dysfunction are limited. OBJECTIVE: To compare the safety and efficacy of IV zoledronic acid and IV pamidronate in patients with hypercalcemia of malignancy with and without renal dysfunction. METHODS: This retrospective cohort study included adults aged =18 years who were hospitalized at UC Davis Medical Center with hypercalcemia of malignancy and received IV bisphosphonates between January 2012 and October 2020. The primary safety outcome was all-grade serum creatinine elevation by day 7. The primary efficacy outcome was complete response, which was defined as the normalization of corrected serum calcium of =10.5 mg/dL, by day 10. The patients were divided into 2 groups based on their creatinine clearance (CrCl), with one group including the patients with renal dysfunction (CrCl <60 mL/min) and the other group with patients without renal dysfunction (CrCl =60 mL/min). The primary statistical analyses were performed using Fisher's exact test. RESULTS: A total of 100 patients met the inclusion criteria, including 50 patients with baseline renal dysfunction and 50 without baseline renal dysfunction. Of the 50 patients with renal dysfunction, 33 (66%) patients received zoledronic acid and 17 (34%) received pamidronate. All-grade serum creatinine elevation (the primary safety end point) was present in 18 (36%) patients with renal dysfunction compared with 14 (28%) patients who did not have renal dysfunction (P = .52). In all, 39 (78%) patients with renal dysfunction had a complete response by day 10 (the primary end point) compared with 33 (66%) patients without renal dysfunction (P = .13). CONCLUSION: No significant difference was observed in all-grade serum creatinine elevation or in complete response by day 10 between the 2 groups in relation to the use of bisphosphonate or baseline renal function. Future prospective studies are needed to inform the optimal bisphosphonate therapy in patients with severe renal dysfunction. [ABSTRACT FROM AUTHOR]

Vitamin D is essential for bone metabolism and has gained popularity since the general population is now more aware of its benefits. Unfortunately, the availability of unregulated vitamin D formulations without prescription increases the risk of inadvertently ingesting excessive doses of vitamin D. Reports of pediatric cases of vitamin D toxicity are scarce in the world literature. We present the case of a 4-years 9-months old boy from a rural town with vitamin D intoxication secondary to ingestion of seven oral vials containing each of them 600,000 Units of cholecalciferol for a period of 8 months. It is important to educate general population about the risks of ingesting vitamin D without medical prescription. In our patient, the most effective treatment strategy was the use of pamidronate., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with prolonged bisphosphonate therapy. Increasing evidence shows that mucosal damage plays an important role in the pathogenesis of MRONJ. This study investigates the combinatorial effects of hydroxyapatite with Tualang honey on cell viability and wound healing in MRONJ., Materials and Methods: The incorporation of Tualang honey into hydroxyapatite was assessed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and field emission scanning electron-energy dispersive X-ray analysis microscopy (FESEM-EDX). The effect of hydroxyapatite combined with Tualang honey on cell viability was determined by WST-1 assay and wound healing was assessed by scratch assay., Results: The incorporation of Tualang honey into hydroxyapatite altered the functional groups, structure, size, morphology, and components of the crystal as evidenced by FTIR, XRD and FESEM-EDX analysis. High concentrations of pamidronic acid inhibit oral fibroblast viability and wound healing. Low and high concentrations of hydroxyapatite demonstrate non-toxicity towards fibroblast cells. Furthermore, hydroxyapatite reversed the action of pamidronic acid on the cells; it increased fibroblast viability but did not close the wound. Tualang honey promotes fibroblast viability and wound closure. However, the addition of Tualang honey is unable to overcome the inhibitory effects of pamidronic acid on fibroblasts. The addition of Tualang honey and hydroxyapatite improved the cell viability and accelerated wound closure of fibroblast exposed to pamidronic acid., Conclusion: These findings demonstrated that the combination treatment protects oral fibroblasts by preventing bisphosphonate toxicity., 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 Elsevier Masson SAS. All rights reserved.)