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Health Science Reports Apr 2024To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab.
BACKGROUND AND AIMS
To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab.
METHODS
This retrospective study included 162 osteoporotic patients treated with denosumab for 24 months between 2013 and 2019. Patients were divided according to the changes in BMD as nonresponders (N group: <3% increase in lumbar spine BMD [LBMD], N group: <0% increase in femoral neck BMD [FNBMD]) or responders (R group: ≥3% increase in LBMD, R group: ≥0% increase in FNBMD).
RESULTS
The respective changes in the LBMD and FNBMD after 24 months of denosumab treatment were 9.3% (95% confidence interval [CI]: 8.1-10.6) and 3.3% (95% CI: 2.1-4.5). Twenty-eight (17.3%) patients were in the N group, and 134 (82.7%) were in the R group. A history of bisphosphonate treatment was a risk factor for being in the N group (odds ratio [OR]: 3.84, 95% CI: 1.38-10.71, = 0.007; adjusted OR: 3.21, 95% CI: 1.01-10.19, = 0.048). Although the N ( = 48; 30.8%) and R ( = 108; 69.2%) groups had similar baseline characteristics, the N group had a significantly higher baseline FNBMD than the R group ( = 0.003). The change in FNBMD was negatively associated with the FNBMD at baseline ( = -0.34, < 0.001). No new osteoporotic fractures occurred in either group during follow-up.
CONCLUSION
In osteoporotic patients receiving denosumab treatment, a history of bisphosphonate treatment was a risk factor for a lack of increase in LBMD, and a higher FNBMD at baseline was negatively associated with the change in FNBMD.
PubMed: 38585014
DOI: 10.1002/hsr2.1993 -
Scientific Reports Apr 2024Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When...
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Denosumab; Retrospective Studies; Osteonecrosis; Bone Density Conservation Agents; Diphosphonates; Necrosis
PubMed: 38575664
DOI: 10.1038/s41598-024-57635-5 -
Archives of Osteoporosis Apr 2024In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions.
BACKGROUND
In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions.
METHODS
A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient's organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline.
RESULTS
Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment.
CONCLUSION
In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 "relatively new statements" that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.
Topics: Humans; Teriparatide; Zoledronic Acid; Osteoporosis; Ethnicity; Hip Fractures
PubMed: 38564062
DOI: 10.1007/s11657-024-01378-3 -
Calcified Tissue International Mar 2024There are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent... (Review)
Review
There are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent approach to dose, drug or route of administration. Meta-analyses suggest that anti-fracture efficacy of such interventions is equivocal. New therapies are undergoing clinical trials, and it is likely that one or more will receive marketing authorisation within the next three to five years. The long-term outcome from such interventions will need to be studied carefully well beyond the period over which the clinical trials are conducted, and a consistent approach to the collection of data in this regard will be needed as a major collaborative effort.
PubMed: 38553634
DOI: 10.1007/s00223-024-01202-7 -
Assessing EGFR-mutated NSCLC with bone metastasis: Clinical features and optimal treatment strategy.Cancer Medicine Apr 2024This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor...
BACKGROUND
This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR-tyrosine kinase inhibitors (TKIs).
METHODS
The study included patients with stage IV EGFR-mutated NSCLC who were receiving first-line treatment with EGFR-TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not.
RESULTS
The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression-free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM.
CONCLUSIONS
The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; ErbB Receptors; Denosumab; Protein Kinase Inhibitors; Mutation; Retrospective Studies; Acrylamides; Aniline Compounds; Indoles; Pyrimidines
PubMed: 38549499
DOI: 10.1002/cam4.7152 -
Journal of Bone Oncology Apr 2024A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient...
Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal.
A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient started on Denosumab 120 mg subcutaneously, once per month with additional loading doses on Days 8 and 15 attempting to avoid below-knee amputation. Twelve doses of Denosumab were administered in 9 months, resulting in resolution of pain, reduction of tumour size and calcification. Hence, the local surgical treatment was delayed and bisphosphonate maintenance therapy was initiated as skin healing was incomplete. The patient was given Zoledronic acid infusions at a dose of 4 mg. After the third infusion, the skin healed. As tumour remained stable, it was decided to continue maintenance. Overall, six doses of Zoledronic acid at 6 months intervals were administrated over 3 years. At the end of the maintenance, the patient experienced no pain and satisfied with her limb function. Since the lesion remained stable over 3 years after Denosumab discontinuation, it was suggested to stop further medical treatment and proceed to active surveillance. The patient's disease is still stable clinical remission with no serious adverse events 41 months after Denosumab cessation and 10 months after the last bisphosphonate infusion. The present case confirmed the high effectiveness of denosumab as induction therapy in advanced recurrent giant cell tumour. We speculate that following the Denosumab-induced tumour ossification, high Zoledronic acid uptake in lesion may prevent tumour reactivation due to its improved pharmacodynamics with an assumed irreversible anti-tumoral effect on residual mutated cells. This hypothesis requires confirmation in future studies.
PubMed: 38545297
DOI: 10.1016/j.jbo.2024.100596 -
Case Reports in Oncology 2024Rare cancers, in aggregate, represent a significant burden of disease in oncology and remain therapeutically challenging to manage due to a lack of clinical trials....
INTRODUCTION
Rare cancers, in aggregate, represent a significant burden of disease in oncology and remain therapeutically challenging to manage due to a lack of clinical trials. Eccrine porocarcinoma is a rare cutaneous sweat-gland malignancy for which there remains no standard approach to metastatic disease.
CASE PRESENTATION
We describe a patient diagnosed with metastatic disease, confirmed on bone biopsy; pathological analysis further revealed this was oestrogen receptor positive. She was commenced on the aromatase inhibitor letrozole, and denosumab, and showed a significant clinical and radiological response on bone scan within 7 months. At the time of report, over 2 years since commencing letrozole, she remains well with no evidence of progression.
CONCLUSION
Our experience adds to the literature suggesting anti-oestrogen therapy can have significant benefit in patients with ER-positive non-breast cancer and is in keeping with increasing interest in therapies agnostic to site of origin but guided by expression/mutation of oncogenic drivers.
PubMed: 38545085
DOI: 10.1159/000535328 -
JBMR Plus Apr 2024Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).
BACKGROUND
Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).
METHODS
We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6 months.
RESULTS
Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change.
CONCLUSION
Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.
PubMed: 38544922
DOI: 10.1093/jbmrpl/ziae016 -
Annals of Joint 2023Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can... (Review)
Review
BACKGROUND AND OBJECTIVE
Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can be divided into categories based on its etiology: senile, post-menopausal, and secondary osteoporosis. Specific prevention measures and treatments exist for targeting bone loss. Here we review and summarize the literature regarding the presentation of osteoporosis and discuss pharmaceutical therapies.
METHODS
PubMed and Google Scholar were searched for articles published in English between 1980 and 2021. Search terms combined "senile osteoporosis", "osteoporosis treatment", "osteoporosis", "bisphosphonates", "denosumab", types of hormone therapy, and other relevant keywords used in various combinations.
KEY CONTENT AND FINDINGS
Osteoporosis affects millions but often goes undiagnosed until a pathologic fracture. Dual-energy X-ray absorptiometry (DEXA) scans evaluate bone mineral density (BMD) and are a diagnostic tool for osteoporosis. Adults over the age of 65, post-menopausal women, and those with risk factors such as previous fractures are recommended to receive DEXA scans every one to two years. Bisphosphonates, denosumab, and hormonal therapies are among the most common pharmacologic treatments for osteoporosis.
CONCLUSIONS
Daily, orally administered bisphosphonates are the first-line therapy for osteoporosis given their efficacy in decreasing fracture risk and favorable safety profile. Denosumab is an alternative that is administered subcutaneously every six months and may be given as initial therapy to select patients. Hormonal therapies are used if patients cannot tolerate bisphosphonates or denosumab or are refractory to these medications. Preventative measures for osteoporosis include tailored exercise and sufficient intake of calcium and vitamin D via diet or supplementation.
PubMed: 38529240
DOI: 10.21037/aoj-23-2 -
The Oncologist Mar 2024Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in...
INTRODUCTION
Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC.
METHODS
Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs.
RESULTS
Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007).
CONCLUSION
A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.
PubMed: 38527096
DOI: 10.1093/oncolo/oyae036