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Nature Reviews. Rheumatology Apr 2024Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent,... (Review)
Review
Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.
Topics: Male; Female; Humans; Osteoporosis; Fractures, Bone; Musculoskeletal Diseases; Osteoarthritis; Bone Density
PubMed: 38485753
DOI: 10.1038/s41584-024-01094-9 -
Pediatric Rheumatology Online Journal Mar 2024Multicentric carpotarsal osteolysis (MCTO) is a rare genetic disorder characterized by the progressive loss of bone in the hands, feet, and other skeletal structures. It... (Review)
Review
BACKGROUND
Multicentric carpotarsal osteolysis (MCTO) is a rare genetic disorder characterized by the progressive loss of bone in the hands, feet, and other skeletal structures. It presents with symptoms that may resemble those of juvenile idiopathic arthritis, making diagnosis challenging for clinicians. The identification of MAF BZIP Transcription Factor B (MAFB) mutations as significant contributors to MCTO represents a major breakthrough in our understanding of the pathogenesis of this rare skeletal disorder.
CASE PRESENTATION
Our objective was to present the phenotype, treatment, and outcome of a patient with a variant of MAFB-induced MCTO to broaden the range of clinical features associated with MCTO and share our clinical experience for improved diagnosis and treatment. In our case, early MRI examination of the bones and whole exome sequencing enabled an early and accurate MCTO diagnosis, and timely Denosumab administration resulted in no deterioration.
CONCLUSION
This suggests that MRI examination and whole exome sequencing should be considered when MCTO is suspected, and Denosumab might be an option in the treatment of MCTO.
Topics: Humans; Osteolysis; Denosumab; Mutation; Phenotype; MafB Transcription Factor
PubMed: 38481224
DOI: 10.1186/s12969-024-00964-6 -
European Journal of Cancer (Oxford,... May 2024Recent evidence suggests additional immunomodulatory properties of RANKL inhibition possibly boosting the clinical efficacy of immune checkpoint inhibitors (ICI).
BACKGROUND
Recent evidence suggests additional immunomodulatory properties of RANKL inhibition possibly boosting the clinical efficacy of immune checkpoint inhibitors (ICI).
METHODS
We conducted a prospective, multicentre clinical trial in unresectable stage IV melanoma patients with bone metastases who received denosumab in parallel with dual ICI (BONEMET) and performed comprehensive immune monitoring at baseline and 4, 12, and 24 weeks after initiation of therapy. Secondary endpoints included tolerability and efficacy. For comparison, biospecimens from melanoma patients treated with dual ICI without denosumab were analyzed accordingly and served as retrospective reference cohort.
RESULTS
In both the BONEMET (n = 16) and the reference cohort (n = 18) serum levels of 17 cytokines, including IFNγ were significantly increased after 4 weeks of treatment. Patients who received ICI and denosumab showed a significantly higher increase in serum CXCL-13 and a significant decrease in VEGFc compared with the reference cohort. While no changes in T cell composition were observed at 4 weeks, patients in the BONEMET cohort showed a significant decrease in the peripheral naïve T-cell population and an increase in CD8 effector cells after 12 weeks. Treatment-related adverse events occurred with comparable frequency (93.8% in the BONEMET cohort versus 83.3% in the reference cohort). 7/16 patients in the BONEMET cohort and 8/18 patients in the reference cohort achieved disease control.
CONCLUSION
Denosumab in combination with dual ICI modulates cytokine expression and T-cell composition in peripheral blood. The upregulation of CXCL-13, a key factor for initiating tertiary lymphoid structures, strengthens the hypothesis that denosumab indeed boost immunological effects.
Topics: Humans; Denosumab; Melanoma; Retrospective Studies; Prospective Studies; Bone Neoplasms
PubMed: 38479119
DOI: 10.1016/j.ejca.2024.113984 -
Journal of Bone and Mineral Research :... Apr 2024Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III... (Comparative Study)
Comparative Study Randomized Controlled Trial
Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.
Topics: Female; Humans; Biosimilar Pharmaceuticals; Bone Density; Bone Density Conservation Agents; Denosumab; Osteoporosis; Osteoporosis, Postmenopausal; Double-Blind Method
PubMed: 38477751
DOI: 10.1093/jbmr/zjae016 -
JCO Global Oncology Mar 2024Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with...
PURPOSE
Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India.
MATERIALS AND METHODS
A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%.
RESULTS
Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between ₹68,254 and ₹73,636.
CONCLUSION
ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.
Topics: Humans; Female; Denosumab; Breast Neoplasms; Diphosphonates; Bone Density Conservation Agents; Cost-Effectiveness Analysis; Imidazoles; Cost-Benefit Analysis; Bone Neoplasms; Zoledronic Acid
PubMed: 38452304
DOI: 10.1200/GO.23.00396 -
Cureus Feb 2024The purpose of this review is to increase awareness about the evolution and development of current trends in the diagnosis and treatment of aneurysmal bone cysts (ABCs).... (Review)
Review
The purpose of this review is to increase awareness about the evolution and development of current trends in the diagnosis and treatment of aneurysmal bone cysts (ABCs). ABCs are benign, but locally aggressive bone tumors that mainly affect children. ABCs comprise 1% of all primary bone tumors and occur most frequently during the first two decades of life. The diagnosis is made using a variety of imaging modalities and has the characteristic features of an expansile, radiolucent lesion that is often seen in the metaphyseal region of the bone and has fluid-fluid levels that are apparent on MRI. In the pediatric population, telangiectatic osteosarcoma and unicameral bone cyst (UBC) are the main differential diagnoses of an ABC. Giant cell tumors (GCTs) also include in differential diagnosis, which often manifest in patients older than 15 and do not penetrate the open physis although they develop after the physeal closure. Imaging alone cannot rule out telangiectatic osteosarcoma; therefore, a biopsy is recommended. A variety of treatment options have been described; traditionally, most patients are treated with curettage and bone grafting. Curettage alone, however, usually results in tumor recurrence following excision. A variety of adjuvants have been utilized with varying degrees of effectiveness to reduce the risk of local recurrence. When a cyst is in the pelvis, its location and size are such that surgery is a very risky option. Selective arterial embolization has significantly contributed to the development of effective treatments for these situations. Embolization or radiation, as well as denosumab therapy, are widely used as therapies for ABCs in anatomic locations where surgery would significantly increase morbidity.
PubMed: 38449944
DOI: 10.7759/cureus.53587 -
The Korean Journal of Internal Medicine Mar 2024Cancer treatment-induced bone loss (CTBL) is associated with anti-tumor treatments, including endocrine therapies, chemotherapeutic treatments, radiotherapy,...
Cancer treatment-induced bone loss (CTBL) is associated with anti-tumor treatments, including endocrine therapies, chemotherapeutic treatments, radiotherapy, glucocorticoids, and tyrosine kinase inhibitors. Osteoporosis, characterized by the loss of bone mass, can increase the risk of fractures, leading to mortality and long-term disability, even after cancer remission. Cancer and osteoporosis have marked clinical and pathogenetic similarities. Both have a multifactorial etiology, affect the geriatric population, and markedly influence quality of life. Lifestyle management, including calcium and vitamin D supplementation, is recommended but the supporting evidence is limited. Oral and injectable bisphosphonates are effective for osteoporosis and malignant bone disease. Bisphosphonates increase bone mineral density (BMD) in patients with CTBL. Denosumab is also used in the management of CTBL; in clinical trials, it improved BMD and reduced the risk of fracture. Currently, there are no bone anabolic therapies for patients with cancer. Appropriate therapies are necessary to maintain optimal bone health, particularly in patients at heightened risk.
PubMed: 38439172
DOI: 10.3904/kjim.2023.386 -
Problemy Endokrinologii Feb 2024Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors....
BACKGROUND
Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia.
AIM
To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT.
MATERIALS AND METHODS
The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy.
RESULTS
There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)).
CONCLUSION
Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.
Topics: Female; Male; Humans; Hypocalcemia; Cholecalciferol; Parathyroidectomy; Hyperparathyroidism, Primary; Parathyroid Hormone; Phosphorus; Vitamin D Deficiency
PubMed: 38433540
DOI: 10.14341/probl13324 -
Supportive Care in Cancer : Official... Mar 2024Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment...
Treatment of bone metastases from solid tumors with bone-modifying agents: a web survey of Italian oncologists investigating patterns of practice drug prescription and prevention of side effects.
PURPOSE
Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ).
METHODS
Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated.
RESULTS
Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered.
CONCLUSION
Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules.
Topics: Male; Humans; Denosumab; Bone Density Conservation Agents; Bone Neoplasms; Diphosphonates; Prostatic Neoplasms; Breast Neoplasms; Drug Prescriptions; Italy
PubMed: 38427111
DOI: 10.1007/s00520-024-08392-8 -
Hip & Pelvis Mar 2024To assess current practice in the treatment of osteoporosis in patients who underwent treatment for hip fracture in South Korea.
PURPOSE
To assess current practice in the treatment of osteoporosis in patients who underwent treatment for hip fracture in South Korea.
MATERIALS AND METHODS
A survey of 97 members of the Korean Hip Society, orthopedic hip surgeons who administer treatment for hip fractures in South Korea, was conducted. The survey was conducted for assessment of demographic data and perceptions regarding the management of osteoporosis in patients who have undergone treatment for hip fracture. Analysis of the data was performed using descriptive statistical methods.
RESULTS
The majority of participants were between the age of 41 and 50 years, and 74% were practicing in tertiary hospitals. Testing for serum vitamin D levels (82%) was the most commonly performed laboratory test. Calcium and vitamin D were prescribed for more than 80% of patients by 47% and 52% of participants, respectively. Denosumab was the most commonly used first-line treatment option for osteoporosis in hip fracture patients. Bisphosphonate was most often perceived as the cause of atypical femoral fractures, and the most appropriate time for reoperation was postoperative 12 months. Teriparatide was most preferred after cessation of bisphosphonate and only prescribing calcium and vitamin D was most common in high-risk patients for prevention of atypical femoral fracture.
CONCLUSION
The results of this study that surveyed orthopedic hip surgeons showed that most participants followed the current strategy for management of osteoporosis. Because the end result of osteoporosis is a bone fracture, active involvement of orthopedic surgeons is important in treating this condition.
PubMed: 38420739
DOI: 10.5371/hp.2024.36.1.62