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Clinical Medicine & Research Jun 2017Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized due to a...
Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized due to a low level of awareness for the disorder. It typically presents with relapsing and remitting pain in the shoulder, neck, and anterior chest wall area with occasional swelling and tenderness of the sternoclavicular area. The diagnosis is confirmed radiologically by sclerosis and hyperostosis of the sternoclavicular joints. There have been several reports in which intravenous bisphosphonates and tumor necrosis factor-inhibitors have shown reasonable efficacy in the treatment of this disorder. We report a patient with a long history of SCCH in whom pamidronate 60 mg intravenously every 3 months for 3 years failed to reduce symptom severity and improve radiologic findings.
Topics: Adult; Diphosphonates; Female; Humans; Hyperostosis, Sternocostoclavicular; Pamidronate; Treatment Failure
PubMed: 28751466
DOI: 10.3121/cmr.2017.1352 -
Cureus Feb 2021Bone is the most common site for distant metastases in breast cancer and can cause significant morbidity and mortality. Bone modifying agents (BMAs) that include... (Review)
Review
Bone is the most common site for distant metastases in breast cancer and can cause significant morbidity and mortality. Bone modifying agents (BMAs) that include bisphosphonates (BPAs) and denosumab help in decreasing and delaying skeletal-related events (SREs) associated with metastatic breast cancer. BPAs approved for use by the Food and Drug Administration (FDA) in bone metastases (BM) in the United States are pamidronate and zolendronic acid, while clodronate and ibandronate are licensed for use in other countries. Current American Society of Clinical Oncology (ASCO) guidelines recommend denosumab 120 mg subcutaneously every four weeks, or zolendronic acid 4 mg every four weeks or every 12 weeks, or intravenous pamidronate 90 mg every four weeks. Current guidelines do not recommend one BMA over another, however, zolendronic acid and denosumab were the most commonly used BMAs in population-based studies. Side effects of BMAs include acute phase reactions, hypocalcemia, nephrotoxicity, osteonecrosis of jaw, etc. While other side effects are common with both BPAs and denosumab, the latter has less nephrotoxic potential and is preferred for use in patients with renal failure. Current ASCO guidelines recommend continuing BMAs indefinitely, however, in clinical practice, this decision needs to be individualized, especially since there is no data on the impact of long-term use of BMAs. Further studies would need to be developed to develop an algorithm of SRE risk assessment and to determine which patients would benefit from BMAs.
PubMed: 33738175
DOI: 10.7759/cureus.13332 -
European Journal of Endocrinology Mar 2021Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association...
OBJECTIVE
Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database.
DESIGN
A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database.
METHODS
Analysis of adverse events reported as 'atrial fibrillation' (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0.
RESULTS
530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17-7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender.
CONCLUSIONS
This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.
Topics: Administration, Intravenous; Aged; Aged, 80 and over; Atrial Fibrillation; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Humans; Male; North America; Pamidronate; Pharmacoepidemiology; Pharmacovigilance; World Health Organization; Zoledronic Acid
PubMed: 33449911
DOI: 10.1530/EJE-20-0650 -
Translational Pediatrics Oct 2017Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its... (Review)
Review
Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.
PubMed: 29184807
DOI: 10.21037/tp.2017.09.10 -
Bone May 2022Bone metastatic disease may lead to serious adverse events in patients with cancer. Bone-directed therapies, including bisphosphonates such as pamidronate and zoledronic... (Review)
Review
Bone metastatic disease may lead to serious adverse events in patients with cancer. Bone-directed therapies, including bisphosphonates such as pamidronate and zoledronic acid and the human monoclonal antibody denosumab, are currently approved for the prevention of bone-related adverse events. However, despite the benefits of these drugs, they may cause side effects that are mostly associated with dosages and treatment durations. These side effects range from more frequent, mostly mild, and generally self-limited side effects-such as fever, myalgias, arthralgias, and electrolyte imbalances-to less frequent and more severe side effects such as medication-related osteonecrosis of the jaw and atypical femoral fractures. The purpose of this review is to familiarize clinicians with the literature regarding adverse events associated with bone-directed therapies in patients with cancer. It is important to be aware of these possible adverse events and to educate patients about the predisposing factors associated with side effects from bone-directed therapies and the preventive measures necessary to decrease the risk of occurrence.
Topics: Antibodies, Monoclonal; Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Diphosphonates; Humans; Pamidronate; Zoledronic Acid
PubMed: 33631354
DOI: 10.1016/j.bone.2021.115901 -
Bio-medical Materials and Engineering 2019Calcium phosphate cement (CPC) has been studied extensively due to its bioactivity and biodegradability. CPC is typically made by a combination of multiple calcium... (Review)
Review
Calcium phosphate cement (CPC) has been studied extensively due to its bioactivity and biodegradability. CPC is typically made by a combination of multiple calcium phosphates that form a paste that sets and hardens in the body after being combined with either water or an aqueous solution. It is highly moldable and easily manipulated, and CPCs possess osteoconductive properties. Due to these characteristics, CPCs offer great promise in bone grafting applications. CPC combined with drugs has a great potential as drug delivery system and has been studied extensively. In this review we have focused on Bisphosphonate-CPC drug delivery system. In addition, we introduce and discuss the potential of studying other bisphosphonates.
Topics: Alendronate; Animals; Biocompatible Materials; Bone Density Conservation Agents; Calcium Phosphates; Diphosphonates; Drug Carriers; Drug Delivery Systems; Etidronic Acid; Humans; Pamidronate; Zoledronic Acid
PubMed: 31006658
DOI: 10.3233/BME-191055 -
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 -
Current Osteoporosis Reports Oct 2017Osteogenesis imperfecta (OI) is a genetic bone disorder resulting in bone fragility. It has a heterogeneous phenotype which typically includes reduced bone mass,... (Review)
Review
PURPOSE OF REVIEW
Osteogenesis imperfecta (OI) is a genetic bone disorder resulting in bone fragility. It has a heterogeneous phenotype which typically includes reduced bone mass, multiple fractures, deformity, and chronic disability. Bisphosphonate treatment remains the first-line medical management, but there is still debate on aspects of its effectiveness. This review summarizes current knowledge about long-term bisphosphonate use in OI with recommendations on clinical application.
RECENT FINDINGS
Bisphosphonates increase bone mineral density, most notably of the vertebrae, and reduce fracture risk in the pediatric OI population. Gains in strength and mobility, together with the permissive effect on orthopedic surgery (e.g., in combination with intramedullary rodding) and physiotherapy, have resulted in improved quality of life for those with OI. As experience in its use continues, the risks and benefits of long-term bisphosphonate treatment in OI are slowly emerging. Patient registries containing data on genotype, phenotype, fractures, bisphosphonate treatment, orthopedic intervention, and functional outcomes are essential for systematic evaluation given the lack of large multi-centered randomized control trials.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Spontaneous; Humans; Imidazoles; Orthopedic Procedures; Osteogenesis Imperfecta; Pamidronate; Physical Therapy Modalities; Quality of Life; Zoledronic Acid
PubMed: 28823022
DOI: 10.1007/s11914-017-0401-0 -
Clinical Genetics Mar 2018SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial... (Review)
Review
SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. We report molecular and phenotypic features of 7 individuals with SAS documented to have low bone mineral density (BMD) ascertained by dual-energy X-ray absorptiometry (DXA), often preceded by tibial bowing. The lowest BMD Z-scores ranged -2.3 to -5.6. In 4 individuals, total alkaline phosphatase levels were elevated (2 with elevated bone fraction) around the time of low BMD documentation. A clinically significant fracture history and a diagnosis of pediatric osteoporosis were present in 4 individuals. Pamidronate treatment in 2 children improved BMD. In conclusion, low BMD, fractures, and tibial bowing are relatively common skeletal complications in individuals with SAS. DXA is a useful tool when evaluating a child with SAS suspected to have low BMD and the results might alter clinical management.
Topics: Adolescent; Bone Density; Bone Development; Bone Diseases, Developmental; Bone and Bones; Child; Child, Preschool; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Matrix Attachment Region Binding Proteins; Phenotype; Radiography; Syndrome; Transcription Factors
PubMed: 28787087
DOI: 10.1111/cge.13121 -
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