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International Journal of Rheumatic... Aug 2023Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an...
Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an African-American adolescent male who presented with recurrent swelling of the temporal region with skull involvement on head imaging, which is atypical for chronic recurrent multifocal osteomyelitis. He had clinical and laboratory improvement after initiation of indomethacin and pamidronate.
Topics: Child; Adolescent; Humans; Male; Osteomyelitis; Diagnostic Imaging; Pamidronate; Skull; Chronic Disease; Recurrence
PubMed: 36843231
DOI: 10.1111/1756-185X.14629 -
Annals of Pediatric Endocrinology &... Feb 2024Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream...
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.
CONCLUSION
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.
PubMed: 38461805
DOI: 10.6065/apem.2346028.014 -
Frontiers in Veterinary Science 2024Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In...
INTRODUCTION
Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL's radiosensitization has not been fully elucidated.
METHODS
We investigated ZOL's ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks).
RESULTS
We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT ( = 0.027).
DISCUSSION
ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.
PubMed: 38362299
DOI: 10.3389/fvets.2024.1237084 -
Toxicology Feb 2024P-glycoprotein (Pgp) is a member of the ATP-binding cassette family of transporters that confers multidrug resistance to cancer cells and is actively involved in the...
P-glycoprotein (Pgp) is a member of the ATP-binding cassette family of transporters that confers multidrug resistance to cancer cells and is actively involved in the pharmacokinetics and toxicokinetics of a big variety of drugs. Extensive studies have provided insights into the binding of many compounds, but the precise mechanism of translocation across the membrane remains unknown; in this context, the major challenge has been to understand the basis for its polyspecificity. In this study, molecular dynamics (MD) simulations of human P-gp (hP-gp) in an explicit membrane-and-water environment were performed to investigate the dynamic behavior of the transporter in the presence of different compounds (active and inactive) in the binding pocket and ATP molecules within the nucleotide binding domains (NBDs). The complexes studied involve four compounds: cyclosporin A (CSA), amiodarone (AMI), pamidronate (APD), and valproic acid (VPA). While CSA and AMI are known to interact with P-gp, APD and VPA do not. The results highlighted how the presence of ATP notably contributed to increased flexibility of key residues in NBD1 of active systems, indicating potential conformational changes activating the translocation mechanism. MD simulations reveal how these domains adapt and respond to the presence of different substrates, as well as the influence of ATP binding on their flexibility. Furthermore, distinctive behavior was observed in the presence of active and inactive compounds, particularly in the arrangement of ATP between NBDs, supporting the proposed nucleotide sandwich dimer mechanism for ATP binding. This study provides comprehensive insights into P-gp behavior with various ligands and ATP, offering implications for drug development, toxicity assessment and demonstrating the validity of the results derived from the MD simulations.
Topics: Humans; Adenosine Triphosphate; ATP Binding Cassette Transporter, Subfamily B; Membrane Glycoproteins; Membrane Transport Proteins; Molecular Dynamics Simulation; Nucleotides; Protein Binding
PubMed: 38272384
DOI: 10.1016/j.tox.2024.153732 -
European Radiology Jan 2024To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO).
Preferential involvement of the pelvis and hips along with active sacroiliitis in chronic nonbacterial osteomyelitis: MRI of 97 patients from a single tertiary referral center.
OBJECTIVE
To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO).
METHODS
Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15 years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study.
RESULTS
Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2 years; age at diagnosis, 10.3 ± 3.3 years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%).
CONCLUSION
Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis.
CLINICAL RELEVANCE STATEMENT
When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible.
KEY POINTS
• Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected.
PubMed: 38180529
DOI: 10.1007/s00330-023-10558-7 -
The British Journal of Oral &... May 2024This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings...
This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings highlight the homogeneous presenting signs and symptoms of an intermittently painful, swollen angle and ramus of the mandible. We present the typical laboratory investigative findings (normal inflammatory markers) and imaging appearances (sclerosis and periosteal oedema). Our paper outlines an investigation protocol, including recommendations for extraoral bone biopsies and systemic magnetic resonance imaging (MRI). We explain the importance of multidisciplinary care, with combined care by rheumatologists and infectious disease specialists. Finally we demonstrate the efficacy of our treatment algorithm for oral non-steroidal anti-inflammatory drugs (NSAIDs), and in those cases refractory to NSAIDS, intravenous pamidronate. This paper provides a useful addition to the literature by informing OMF surgeons of this rare condition and given the clinical equipoise in treatments, it can hopefully guide clinicians in an investigation pathway and management protocol.
Topics: Humans; Osteomyelitis; Child; Male; Mandibular Diseases; Female; Chronic Disease; Adolescent; Magnetic Resonance Imaging; Child, Preschool; Algorithms; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38599930
DOI: 10.1016/j.bjoms.2023.12.022 -
Proceedings (Baylor University. Medical... 2024Breast 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)...
BACKGROUND
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.
METHODS
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.
RESULTS
There was no statistical difference for an increased risk in pathological fractures (2.7% vs. 2.8%, = 0.88), spinal cord compression (2.6% vs. 2.7%, = 0.88), or 5-year survival rate (45.5% vs. 52.4%, = 0.78) for the denosumab cohort versus the pamidronate cohort.
CONCLUSION
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.
PubMed: 38174029
DOI: 10.1080/08998280.2023.2276623 -
Successful Management of Severe Hypercalcemia with Zoledronic Acid: A Report of Two Pediatric Cases.Journal of Clinical Research in... May 2024Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with...
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.
Topics: Humans; Zoledronic Acid; Hypercalcemia; Bone Density Conservation Agents; Female; Male; Child; Child, Preschool; Treatment Outcome; Diphosphonates; Hypocalcemia; Imidazoles
PubMed: 36264042
DOI: 10.4274/jcrpe.galenos.2022.2022-9-3 -
BMC Veterinary Research May 2024Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an...
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.
Topics: Animals; Dogs; Pamidronate; Hypocalcemia; Male; Hypercalcemia; Dog Diseases; Glucocorticoids; Bone Density Conservation Agents; Diphosphonates
PubMed: 38790012
DOI: 10.1186/s12917-024-04030-x -
Burns : Journal of the International... Aug 2024To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; Burns; Body Composition; Child; Muscle Strength; Body Weight; Body Height; Exercise Therapy; Nutritional Support; Treatment Outcome
PubMed: 38580580
DOI: 10.1016/j.burns.2024.03.012