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Cureus May 2024Atypical fractures are gaining attention as a severe potential side effect of long-term treatment with bone-modifying agents (e.g., bisphosphonate and denosumab) for...
Atypical fractures are gaining attention as a severe potential side effect of long-term treatment with bone-modifying agents (e.g., bisphosphonate and denosumab) for osteoporosis. Most atypical fractures occur in weight-bearing bones; the femur is the most frequent site. Atypical fractures occurring in non-weight-bearing bones are extremely rare. We describe an atypical fracture of the scapular spine in a 92-year-old Japanese woman with osteoporosis who had been treated with minodronate for ~7 years. Although the dislocation of the fracture site remained after conservative treatment, there was no obstacle to her daily life.
PubMed: 38872707
DOI: 10.7759/cureus.60237 -
Spine Surgery and Related Research May 2024
PubMed: 38868790
DOI: 10.22603/ssrr.2023-0259 -
Cureus May 2024Introduction Medication-related osteonecrosis of the jaw (MRONJ) develops from odontogenic infection. However, there are also some cases of MRONJ developing from sites...
Introduction Medication-related osteonecrosis of the jaw (MRONJ) develops from odontogenic infection. However, there are also some cases of MRONJ developing from sites with no teeth, no root canal lesions, or no periodontal disease. This study aimed to retrospectively review radiographic images of MRONJ cases and examine the differences in characteristics between MRONJ suspected to be related to dental infection (odontogenic MRONJ) and MRONJ that occurred without dental involvement or of unknown cause (non-odontogenic MRONJ). Materials and methods One hundred and forty-five patients were diagnosed with MRONJ at Kansai Medical University Hospital and Kansai Medical University Medical Center. The following variables were investigated: sex, age, primary disease, MRONJ site, body mass index, smoking habit, diabetes, corticosteroids, type of antiresorptive agent, administration period, CT findings (separation of sequestrum, osteolysis, periosteal reaction, and osteosclerosis), trigger, leukocytes, neutrocytes, neutrophil-lymphocyte ratio, serum albumin, and serum creatinine levels. Results In the univariate analysis, significant differences between odontogenic and non-odontogenic MRONJs were found in patients whose primary disease was malignancy, receiving denosumab (DMB), and with short administration period of antiresorptive agent, no osteolysis, periosteal reaction, and serum creatinine level. In multivariate analysis, non-odontogenic MRONJ was significantly more common in patients with no osteolysis and with periosteal reaction. Conclusion Non-odontogenic MRONJ tends to occur more frequently in patients treated with high-dose DMB, and there were significantly more cases of non-osteolytic MRONJ without radiographic evidence of osteolysis or with periosteal reactions.
PubMed: 38868238
DOI: 10.7759/cureus.60223 -
Scientific Reports Jun 2024Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related...
Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.
Topics: Humans; Male; Prostatic Neoplasms; Risk Factors; Aged; Incidence; Bisphosphonate-Associated Osteonecrosis of the Jaw; Denosumab; Bone Neoplasms; Bone Density Conservation Agents; Middle Aged; Zoledronic Acid; Aged, 80 and over; Retrospective Studies
PubMed: 38862617
DOI: 10.1038/s41598-024-64440-7 -
Annals of Medicine and Surgery (2012) Jun 2024Denosumab is known to enhance callus formation while delaying remodeling. However, its effects on fracture healing are scarcely reported in the literature. This case...
BACKGROUND
Denosumab is known to enhance callus formation while delaying remodeling. However, its effects on fracture healing are scarcely reported in the literature. This case report, to the best of our knowledge, is the first to report the potential effect of denosumab on a metatarsal fracture in an older adult patient, 4 months after administration, resulting in a favorable clinical course with early weight-bearing 17 days after the fracture.
PRESENTATION OF CASE
A 73-year-old female sustained a right-foot second metatarsal fracture due to the fall of a heavy object. She has a history of diabetes mellitus, hypertension, and osteoporosis. Prior to sustaining the fracture, she received seven doses of denosumab spaced 6 months apart, with the last dose administered 4 months earlier. Furthermore, the patient was treated with a backsplint for 6 weeks. After 17 days, follow-up radiographs showed a large callus formation, with no pain and the ability to bear weight. Subsequent radiographs revealed a large callus with delayed remodeling.
DISCUSSION
This case report suggests that denosumab remains effective for promoting rapid callus formation even 4 months after administration for osteoporosis, despite delayed remodeling. This delay did not seem to have negative effects on the clinical outcomes, as the patient achieved weight-bearing within 17 days after sustaining the fracture.
CONCLUSION
Denosumab may positively influence fracture healing in older adults with metatarsal fractures, potentially leading to delayed remodeling. However, further studies are needed to confirm these observations.
PubMed: 38846825
DOI: 10.1097/MS9.0000000000002134 -
Hong Kong Medical Journal = Xianggang... Jun 2024
PubMed: 38841765
DOI: 10.12809/hkmj2210652 -
Regenerative Therapy Dec 2024Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used...
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration . We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration . Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA.
PubMed: 38840731
DOI: 10.1016/j.reth.2024.03.019 -
Bone Jun 2024Osteoporosis (OP) is a chronic progressive bone disease which is characterized by reduction of bone matrix volume and changes in the bone matrix properties which can... (Review)
Review
Osteoporosis (OP) is a chronic progressive bone disease which is characterized by reduction of bone matrix volume and changes in the bone matrix properties which can ultimately lead to bone fracture. The two major forms of OP are related to aging and/or menopause. With the worldwide increase of the elderly population, particularly age-related OP poses a serious health issue which puts large pressure on health care systems. A major challenge for development of new drug treatments for OP and comparison of drug efficacy with existing treatments is due to current regulatory requirements which demand testing of drugs based on bone mineral density (BMD) in phase 2 trials and fracture risk in phase 3 trials. This requires large clinical trials to be conducted and to be run for long time periods, which is very costly. This, together with the fact that there are already many drugs available for treatment of OP, makes the development of new drugs inhibitive. Furthermore, an increased trend of the use of different sequential drug therapies has been observed in OP management, such as sequential anabolic-anticatabolic drug treatment or switching from one anticatabolic drug to another. Running clinical trials for concurrent and sequential therapies is neither feasible nor practical due to large number of combinatorial possibilities. In silico mechanobiological pharmacokinetic-pharmacodynamic (PK-PD) models of OP treatments allow predictions beyond BMD, i.e. bone microdamage and degree of mineralisation can also be monitored. This will help to inform clinical drug usage and development by identifying the most promising scenarios to be tested clinically (confirmatory trials rather than exploratory only trials), optimise trial design and identify subgroups of the population that show benefit-risk profiles (both good and bad) that are different from the average patient. In this review, we provide examples of the predictive capabilities of mechanobiological PK-PD models. These include simulation results of PMO treatment with denosumab, implications of denosumab drug holidays and coupling of bone remodelling models with calcium and phosphate systems models that allows to investigate the effects of co-morbidities such as hyperparathyroidism and chronic kidney disease together with calcium and vitamin D status on drug efficacy.
PubMed: 38838799
DOI: 10.1016/j.bone.2024.117140 -
Saudi Medical Journal Jun 2024Chondroblastoma is a rare benign cartilaginous tumor that accounts for approximately 1% of bone tumors, but it can be associated with lung metastasis in extremely rare...
Chondroblastoma is a rare benign cartilaginous tumor that accounts for approximately 1% of bone tumors, but it can be associated with lung metastasis in extremely rare cases, leading to a poor prognosis and death. Herein, we report the case of a 19-year-old male patient who presented with an aggressive chondroblastoma of the proximal humerus and bilateral lung metastasis. The patient was treated with wide local resection, partial metastasectomy, and denosumab. Denosumab treatment was effective in controlling metastatic progression and preventing local recurrence.
Topics: Humans; Male; Bone Neoplasms; Lung Neoplasms; Denosumab; Chondroblastoma; Young Adult; Humerus; Bone Density Conservation Agents
PubMed: 38830665
DOI: 10.15537/smj.2024.45.6.20230720 -
JBMR Plus Jul 2024The coronavirus disease 2019 (COVID-19) pandemic triggered significant disruptions in health care systems around the world, with a particularly heavy impact on patients...
The coronavirus disease 2019 (COVID-19) pandemic triggered significant disruptions in health care systems around the world, with a particularly heavy impact on patients with chronic diseases. A number of studies have shown an immediate decrease in on-time denosumab therapy at the start of COVID-19 pandemic. However, independent of the "emergency" that occurred during the COVID-19 pandemic, there are other situations in which denosumab is discontinued. In such situations, it is important to have a programmed strategy to optimize care while limiting the risk for unwanted outcomes.
PubMed: 38827117
DOI: 10.1093/jbmrpl/ziae046