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Endocrinology and Metabolism (Seoul,... Oct 2022Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries,...
Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.
Topics: Humans; Osteitis Deformans; Diphosphonates; Pamidronate; Bone and Bones; Bone Resorption
PubMed: 36327984
DOI: 10.3803/EnM.2022.1575 -
The Cochrane Database of Systematic... Oct 2016Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias of the included trials.
MAIN RESULTS
Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months.
AUTHORS' CONCLUSIONS
Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.
Topics: Administration, Oral; Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Injections, Intravenous; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 27760454
DOI: 10.1002/14651858.CD005088.pub4 -
BMJ Case Reports Jan 2020In 2003, Marx reported the first case of osteonecrosis of the jaw in 36 cases related to zoledronic acid or pamidronate. Painful bone exposure in the mandible or maxilla...
In 2003, Marx reported the first case of osteonecrosis of the jaw in 36 cases related to zoledronic acid or pamidronate. Painful bone exposure in the mandible or maxilla unresponsive to medical or surgical management was observed. In 2014, the American Association of Oral and Maxillofacial Surgeons proposed the term 'medication-related osteonecrosis of the jaw' (MRONJ). However, a non-exposed variant may also occur. MRONJ can lead to debilitating clinical sequelae with limited treatment options. We present the case of a 73-year-old woman with metastatic breast cancer and MRONJ of her mandible and maxilla following treatment with intravenous zoledronic acid and denosumab. Six months following dental extractions, she was referred to the Department of Oral and Maxillofacial Surgery for assessment of extensive necrosis of her maxilla and mandible. Extraoral draining sinuses were observed. A CT mandible showed cortical destruction with an ill-defined mixed sclerotic-lucent pattern in keeping with osteonecrosis. Due to her metastatic breast cancer, the extent of her necrosis and poor performance status, free flap reconstruction of her mandible was ruled out. She was treated conservatively.
Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Breast Neoplasms; Denosumab; Diagnosis, Differential; Fatal Outcome; Female; Humans; Mandible; Maxilla; Tomography, X-Ray Computed; Tooth Extraction
PubMed: 31907213
DOI: 10.1136/bcr-2018-224455 -
Lancet (London, England) Oct 2015Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer.
METHODS
We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs).
FINDINGS
We received data on 18,766 women (18,206 [97%] in trials of 2-5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87-1·01; 2p=0·08), distant recurrence (0·92, 0·85-0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83-0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73-0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78-0·94; 2p=0·002), distant recurrence (0·82, 0·74-0·92; 2p=0·0003), bone recurrence (0·72, 0·60-0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73-0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75-0·97; 2p=0·02).
INTERPRETATION
Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began.
FUNDING
Cancer Research UK, Medical Research Council.
Topics: Bone Density Conservation Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Drug Administration Schedule; Female; Humans
PubMed: 26211824
DOI: 10.1016/S0140-6736(15)60908-4 -
Molecules (Basel, Switzerland) Nov 2022[F]sodium fluoride ([F]NaF) is recognised to be superior to [mTc]-methyl diphosphate ([Tc]Tc-MDP) and ([F]FDG) in bone imaging. However, there is concern that [F]NaF...
[F]sodium fluoride ([F]NaF) is recognised to be superior to [mTc]-methyl diphosphate ([Tc]Tc-MDP) and ([F]FDG) in bone imaging. However, there is concern that [F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (/), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [F]AlF-NOTA-pamidronic acid was as sensitive as [F]sodium fluoride ([F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [F]NaF was higher in both cell lines, but [F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
Topics: Humans; Fluorine Radioisotopes; Pamidronate; Sodium Fluoride; Chromatography, Liquid; Heterocyclic Compounds; Oligopeptides; Tandem Mass Spectrometry; Positron-Emission Tomography
PubMed: 36432069
DOI: 10.3390/molecules27227969 -
CMAJ : Canadian Medical Association... Mar 2024
Topics: Humans; Scleritis; Pamidronate; Uveitis, Anterior; Acute Disease
PubMed: 38527748
DOI: 10.1503/cmaj.230859-f