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Annals of Oncology : Official Journal... May 2005Breast cancer is the leading type of cancer among women, and bone metastases are common in patients with breast cancer, affecting more than half of all patients with... (Review)
Review
Breast cancer is the leading type of cancer among women, and bone metastases are common in patients with breast cancer, affecting more than half of all patients with advanced disease. Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and hypercalcaemia of malignancy. Bisphosphonates significantly reduced the incidence of these events. Zoledronic acid, pamidronate, clodronate and ibandronate have demonstrated efficacy compared with placebo. Zoledronic acid has also been compared with another active bisphosphonate (i.e. pamidronate) and shown by multiple event analysis to be significantly more effective at reducing the risk of SREs. Bisphosphonates effectively reduce and prevent skeletal complications in patients with bone metastases from breast cancer. Preclinical data suggest that bisphosphonates have antitumour effects. Bisphosphonates may also be of use in the adjuvant setting.
Topics: Administration, Oral; Bone Neoplasms; Breast Neoplasms; Clodronic Acid; Diphosphonates; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Ibandronic Acid; Imidazoles; Infusions, Intravenous; Neoplasm Staging; Pamidronate; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Treatment Outcome; Zoledronic Acid
PubMed: 15802276
DOI: 10.1093/annonc/mdi162 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3 -
EJNMMI Radiopharmacy and Chemistry 2017Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with...
BACKGROUND
Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing Ga-labelled analogues, endoradiotheraphy with Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases.
METHODS
Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA and DOTA(MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide Ga and the β emitting nuclide Lu and compared in studies and in biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats.
RESULTS
The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed Ga and >98 % with Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [Ga]DOTA (SUV = 5.4 ± 0.6) followed by [F]NaF (SUV = 4.8 ± 0.2), [Ga]DOTA (SUV = 4.5 ± 0.2) and [Ga]BPAPD (SUV = 3.2 ± 0.3). [Lu]DOTA showed a similar distribution as the diagnostic Ga complex.
CONCLUSION
The Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [Ga]DOTA, which makes this compound probably an interesting bone targeting agent for a therapeutic approach with Lu. The therapeutic compound [Lu]DOTA showed a high target-to-background ratio. SPECT experiments showed concordance to the PET scans in healthy rats. [Ga/Lu]DOTA appears to be a potential theranostic combination in the management of disseminated bone metastases.
PubMed: 29564390
DOI: 10.1186/s41181-016-0017-1 -
Burns : Journal of the International... Dec 2018Severe burns in children can lead to growth delays, bone loss, and wasting of lean body mass and muscle with subsequent long-term effects such as osteoporosis. The... (Review)
Review
Severe burns in children can lead to growth delays, bone loss, and wasting of lean body mass and muscle with subsequent long-term effects such as osteoporosis. The following review examines 11 randomized, placebo-controlled, prospective clinical trials in pediatric burns between 1995 and 2017. These studies included approximately 250 burned children, and they were conducted to evaluate the impact of severe burn on markers of bone formation and bone metabolism. Some trials also analyzed current therapy regimens such as pamidronate and vitamin D. The clinical utility of these outlined biomarkers is uncertain with regard to acute burn care, as the current literature remains unclear. This review thus serves to address the impact of severe burn on markers of bone formation and bone metabolism in pediatric patients but will not focus on the clinical utility of the markers. The aim of this review is to summarize the findings of the trials to guide the future care of burned patients to maximize bone recovery.
Topics: Adaptor Proteins, Signal Transducing; Aluminum; Body Composition; Bone Density; Bone Density Conservation Agents; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Remodeling; Bone and Bones; Burns; Calcium; Child; Collagen Type I; Copper; Genetic Markers; Glucocorticoids; Humans; Magnesium; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Pamidronate; Parathyroid Hormone; Vitamin D; Zinc
PubMed: 30077487
DOI: 10.1016/j.burns.2018.04.014 -
Orphanet Journal of Rare Diseases Jul 2023Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging,...
BACKGROUND
Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.
METHODS
A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.
RESULTS
36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments.
CONCLUSIONS
Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.
Topics: Child; Adult; Humans; Osteitis; Pamidronate; Osteomyelitis; Acquired Hyperostosis Syndrome; Hyperostosis; Inflammation
PubMed: 37480122
DOI: 10.1186/s13023-023-02831-1 -
Scientific Reports Jul 2023Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for...
Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for osteoporosis currently. However, further evidence is needed to learn more regarding other common anti-osteoporosis drugs and the risk for AFF. In this study, reports of AFF were identified from Food and Drug Administration Adverse Event Reporting System database. Disproportionality analyses were performed to examine the reporting odds ratio (ROR), information component (IC) and adjusted ROR (adj. ROR) signals for AFF for common anti-osteoporosis drugs. A total of 1692 unique AFF reports were identified. The disproportionality signals (the lower bound of 95% confidence interval > 1 for ROR and adjusted ROR, and > 0 for IC) were detected for alendronate, denosumab, pamidronate, risedronate, zoledronate, ibandronate, and teriparatide while no signal was detected for raloxifene, abaloparatide, and romosozumab. When restricted in patients with osteoporosis, the disproportionality signals were still detected for alendronate, pamidronate, risedronate, denosumab, and ibandronate. Our results suggest that alendronate has the largest risk signal, while the risks varied among different bisphosphonates. In addition, denosumab was found statistically associated with AFF in both the entire database and patients with osteoporosis.
Topics: Humans; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Denosumab; Ibandronic Acid; Pharmaceutical Preparations; Pamidronate; Osteoporosis; Diphosphonates; Femur
PubMed: 37407650
DOI: 10.1038/s41598-023-37944-x -
The Pan African Medical Journal 2015
Topics: Bone Density Conservation Agents; Chromogranins; Diphosphonates; Fibrous Dysplasia of Bone; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Pamidronate
PubMed: 26401215
DOI: 10.11604/pamj.2015.21.21.3487 -
The New England Journal of Medicine Jul 2003
Topics: Alkaline Phosphatase; Bone Density; Bone Marrow; Calcium; Child; Diphosphonates; Humans; Male; Osteopetrosis; Pamidronate; Phosphorus Metabolism Disorders; Radiography; Radionuclide Imaging
PubMed: 12890844
DOI: 10.1056/NEJMoa023110 -
BMJ Case Reports Sep 2017Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown...
Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown aetiology present in previously well children and is a diagnosis of exclusion. We describe a 10-year-old prepubertal boy who presented with back pain of 1-week duration. His spinal X-ray showed generalised loss of vertebral body heights in keeping with osteoporosis. Endocrine and haematological work-up were normal. He was treated with vitamin D supplement and intravenous pamidronate. This case illustrates the general work-up and causes for paediatric osteoporosis, and the management for idiopathic juvenile osteoporosis.
Topics: Administration, Intravenous; Back Pain; Bone Density Conservation Agents; Child; Diagnosis, Differential; Diphosphonates; Humans; Male; Osteoporosis; Pamidronate; Radiography; Spine; Treatment Outcome; Vitamin D
PubMed: 28866630
DOI: 10.1136/bcr-2017-220700 -
ACS Omega Mar 2021Organophosphorous compounds are still widely used as potential scale inhibitors in the upstream oil and gas industry, particularly in squeeze treatments as they have...
Organophosphorous compounds are still widely used as potential scale inhibitors in the upstream oil and gas industry, particularly in squeeze treatments as they have good adsorption properties on rock and are easily detectable. However, most phosphonate-based scale inhibitors have some drawbacks, such as poor biodegradability and various incompatibilities with the production system. The low toxicity of bisphosphonates motivated us to test a series of aliphatic and aromatic hydroxybisphosphonates as new oilfield scale inhibitors for calcium carbonate (calcite) and barium sulfate (barite) scales. Thus, the well-known bone-targeting drugs 3-amino-1-hydroxypropane-1,1-bisphosphonic acid (pamidronic acid, ), 4-amino-1-hydroxybutane-1,1-bisphosphonic acid (alendronic acid, ), 5-amino-1-hydroxypentane-1,1-bisphosphonic acid (), and hydroxyphenylmethylene-1,1-bisphosphonic acid (fenidronic acid, ) are studied along with novel, specially designed bisphosphonates (1,4-dihydroxybutane-1,1,4,4-tetrayl)tetrakisphosphonic acid (), (1,6-dihydroxyhexane-1,1,6,6-tetrayl)tetrakisphosphonic acid (), and ((4- aminophenyl)(hydroxy)methylene)bisphosphonic acid () in a dynamic tube-blocking scale rig at 100 °C and 80 bar according to typical North Sea conditions. The scale inhibition performance of the new SIs was compared to that of the commercial 1-hydroxyethylidene bisphosphonic acid () and aminotrismethylenephosphonic acid (). The results indicate that all synthesized hydroxybisphosphonates provide reasonable inhibition performance against calcite scaling and show good thermal stability at 130 °C for 7 days under anaerobic conditions.
PubMed: 33718740
DOI: 10.1021/acsomega.1c00379