- Pre-treatment with Pamidronate Improves Bone Mechanical Properties in Mdx Mice Treated with Glucocorticoids. [Journal Article]
- CTCalcif Tissue Int 2018 Oct 09
- Duchenne muscular dystrophy (DMD) is an X-linked disease of progressive muscle deterioration and weakness. Patients with DMD have poor bone health which is partly due to treatment with glucocorticoid...
Duchenne muscular dystrophy (DMD) is an X-linked disease of progressive muscle deterioration and weakness. Patients with DMD have poor bone health which is partly due to treatment with glucocorticoids, a standard therapy to prolong muscle function that also induces bone loss. Bisphosphonates are used to treat adults at risk of glucocorticoid-induced osteoporosis but are not currently used in DMD patients until after they sustain fractures. In this study, C57BL/10ScSn-mdx mice, a commonly used DMD animal model, received continuous glucocorticoid, prednisone treatment (0.083 mg/day) from 5 to 10 weeks of age. Pre-treatment with the bisphosphonate pamidronate started at 4 weeks of age over a period of 2 weeks or 6 weeks (cumulative dose 8 mg/kg for both) to assess the effectiveness of the two dosing regimens in ameliorating glucocorticoid-induced bone loss. Mdx mice treated with prednisone had improved muscle function that was not changed by pamidronate treatment. Glucocorticoid treatment caused cortical bone loss and decreased cortical bone strength. Both 2 and 6 week pamidronate treatment increased cortical thickness and bone area compared to prednisone-treated Mdx mice, however, only 2 week pamidronate treatment improved the strength of cortical bone compared to that of glucocorticoid-treated Mdx mice. In the trabecular bone, both pamidronate treatments significantly increased the amount of bone, and increased the ultimate load but not the energy to fail. These results highlight the importance of when and how much bisphosphonate is administered prior to glucocorticoid exposure.
- Mining directional drug interaction effects on myopathy using the FAERS database. [Journal Article]
- IJIEEE J Biomed Health Inform 2018 Oct 08
- Mining high-order drug-drug interaction (DDI) induced adverse drug effects from electronic health record (EHR) databases is an emerging area, and very few studies have explored the relationships betw...
Mining high-order drug-drug interaction (DDI) induced adverse drug effects from electronic health record (EHR) databases is an emerging area, and very few studies have explored the relationships between high-order drug combinations. We investigate a novel pharmacovigilance problem for mining directional DDI effects on myopathy using the FDA Adverse Event Reporting System (FAERS) database. Our work provides information on the risk of myopathy associated with adding new drugs on the already prescribed medication, and visualizes the identified directional DDI patterns as user-friendly graphical representation. We utilize the Apriori algorithm to extract frequent drug combinations from the FAERS database. We use odds ratio (OR) to estimate the risk of myopathy associated with directional DDI. We create a tree-structured graph to visualize the findings for easy interpretation. Our method confirmed myopathy association with previously reported HMG-CoA reductase inhibitors like rosuvastatin, fluvastatin, simvastatin and atorvastatin. New, previously unidentified but mechanistically plausible associations with myopathy were also observed, such as the DDI between pamidronate and levofloxacin. Additional top findings are gadolinium-based imaging agents, which however are often used in myopathy diagnosis. Other DDIs with no obvious mechanism are also reported, such as that of sulfamethoxazole with trimethoprim and potassium chloride. This study shows the feasibility to estimate high-order directional DDIs in a fast and accurate manner. The results of the analysis could become a useful tool in the specialists' hands through an easy-to-understand graphic visualization.
- Use of bone-modifying agents among breast cancer patients with bone metastasis: evidence from oncology practices in the US. [Journal Article]
- CEClin Epidemiol 2018; 10:1349-1358
- CONCLUSIONS: The majority of women diagnosed with bone metastasis from breast cancer initiate a BMA within 1 year of diagnosis, but a large proportion, particularly among the elderly, do not use these therapies.
- Efficacy and safety of de-escalation bone- modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis. [Journal Article]
- CMCancer Manag Res 2018; 10:3809-3823
- CONCLUSIONS: In this meta-analysis of randomized clinical trials, the results "appeared" to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.
- Management of multiple myeloma bone disease: impact of treatment on renal function. [Journal Article]
- ERExpert Rev Hematol 2018 Oct 04
- Bone disease (BD) is one of the most common features of multiple myeloma. 70-80% of patients at diagnosis present with lytic lesions which may lead to skeletal-related events. Areas covered: The aim ...
Bone disease (BD) is one of the most common features of multiple myeloma. 70-80% of patients at diagnosis present with lytic lesions which may lead to skeletal-related events. Areas covered: The aim of this review is to present the possible adverse profile of bisphosphonates (BPs) on renal function, the underlying mechanisms by which BPs may affect renal function and the novel therapeutic approaches on myeloma bone disease management. Expert Commentary: BPs remain the cornerstone in the management of myeloma-related BD. Zoledronic acid and Pamidronate are currently the gold standard, however cannot be used in patients with severe renal dysfunction. Renal impairment is another hallmark of myeloma with approximately 60% of the patients presenting with or developing renal dysfunction during the disease course. Although BPs rarely cause renal impairment, they should be administered with caution in patients with impaired renal function. The exact mechanism by which BPs cause renal impairment is yet to be elucidated. Another promising agent is denosumab, a RANKL inhibitor, which can be administrated regardless of renal function and does not need the relevant dose-adjustments.
- Evaluation of Zoledronate as Treatment for Hypercalcemia in Four Dogs. [Journal Article]
- JAJ Am Anim Hosp Assoc 2018 Oct 01
- Hypercalcemia is a biochemical abnormality that, when left untreated, can lead to life-threatening complications including renal failure. Bisphosphonates are routinely used to treat hypercalcemia, bu...
Hypercalcemia is a biochemical abnormality that, when left untreated, can lead to life-threatening complications including renal failure. Bisphosphonates are routinely used to treat hypercalcemia, but most literature on veterinary patients describes the use of pamidronate. This retrospective case series describes the use of zoledronate for treatment of hypercalcemia in four dogs. Information including signalment, clinical signs, treatment, and outcome was collected. All dogs showed a decrease in total and ionized calcium concentrations after treatment with zoledronate. All treatments of zoledronate administered were well tolerated, but a previously unreported local hypersensitivity reaction was observed in one dog. This report is the first to document the efficacy of zoledronate for treatment of hypercalcemia in dogs.
- Williams syndrome with severe hypercalcaemia. [Journal Article]
- BCBMJ Case Rep 2018 Sep 27; 2018
- We present an 11-month-old girl child with complaints of constipation, cough, fever, vomiting and growth retardation. On examination, she had facial dysmorphism, hypertension and murmur. The genetic ...
We present an 11-month-old girl child with complaints of constipation, cough, fever, vomiting and growth retardation. On examination, she had facial dysmorphism, hypertension and murmur. The genetic evaluation showed 7q microdeletion specific to Williams syndrome. Abdominal imaging was suggestive of nephrocalcinosis which is rare for this age group. The baby was managed symptomatically and specific treatment like pamidronate, calcitonin and steroid therapy were also administered to reduce hypercalcaemia. Severe hypercalcaemia with associated hypertension and nephrocalcinosis is very rare. Hence, we emphasise here the importance of early detection of these features and their appropriate management for a better outcome of the patient.
- Cyclic bisphosphonate therapy reduces pain and improves physical functioning in children with osteogenesis imperfecta. [Journal Article]
- BMBMC Musculoskelet Disord 2018 Sep 24; 19(1):344
- CONCLUSIONS: In children with OI, cyclic intravenous bisphosphonate therapy transiently reduces pain and improves functional abilities. Pain relief occurs immediately following infusion with functional improvements observed 4 weeks later. Both pain and physical functioning return to pretreatment levels by the subsequent infusion.
- A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations. [Journal Article]
- BRBone Rep 2018; 9:132-135
- Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2. Rece...
Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2. Recent investigations have discovered several other autosomal recessive genes responsible for OI. Among these genes is LEPRE1, which is involved in post-translational modifications of collagen. To date, more than 40 LEPRE1 mutations have been described. One of these mutations is carried by 1.5% of West Africans and 0.4% of African Americans, and is associated with OI Type VIII. We describe the case of a five year old male with a moderate form of OI and compound heterozygous LEPRE1 mutations (c.1080 + 1G > T; c.1646 T > G, p.Met549Arg). He was diagnosed shortly after birth following a skeletal survey demonstrating multiple healing fractures as well as lower extremity deformity suggestive of remote fractures. He was then without a fracture until a calvarial fracture at 18 months of age, a femur fracture at 4 years and seven months and a second femur fracture at 5 years and 4 months. He walked at age 14 months and has been an active boy. Pamidronate infusions began at seven weeks of age and were discontinued at three years of age due to increased bone mineral density and absence of fractures. Type VIII OI typically causes a severe to lethal phenotype presenting at birth with severe osteopenia, congenital fractures and other clinical manifestations. Only a few individuals have survived to childhood. This case description serves to expand the clinical phenotyping of this recessive form of OI into the more moderate spectrum.
New Search Next
- Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes. [Journal Article]
- ACAging Cell 2018 Sep 14; :e12835
- Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging that recapitulates many normal aging characteristics. This disorder is caused by mutation in the LMNA gene leading to the produ...
Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging that recapitulates many normal aging characteristics. This disorder is caused by mutation in the LMNA gene leading to the production of progerin which induces misshapen nuclei, cellular senescence, and aging. We previously showed that the phospholipase A2 receptor (PLA2R1) promotes senescence induced by replicative, oxidative, and oncogenic stress but its role during progerin-induced senescence and in progeria is currently unknown. Here, we show that knockdown of PLA2R1 prevented senescence induced by progerin expression in human fibroblasts and markedly delayed senescence of HGPS patient-derived fibroblasts. Whole-body knockout of Pla2r1 in a mouse model of progeria decreased some premature aging phenotypes, such as rib fracture and decreased bone content, together with decreased senescence marker. Progerin-expressing human fibroblasts exhibited a high frequency of misshapen nuclei and increased farnesyl diphosphate synthase (FDPS) expression compared to controls; knockdown of PLA2R1 reduced the frequency of misshapen nuclei and normalized FDPS expression. Pamidronate, a FDPS inhibitor, also reduced senescence and misshapen nuclei. Downstream of PLA2R1, we found that p53 mediated the progerin-induced increase in FDPS expression and in misshapen nuclei. These results suggest that PLA2R1 mediates key premature aging phenotypes through a p53/FDPS pathway and might be a new therapeutic target.