Bone Pain Research Articles

A scoping review of the management of prostate cancer in Africa

Prostate cancer is one of the most frequently diagnosed cancers in menand a major cause of cancer-related deaths in men, globally. The managementof prostate cancer in Africa is unique; most patients present withadvanced disease as result of a largely under-developed healthcare delivery.However, due to the underdeveloped healthcare system in Africa,there are unique limitations to delivering these treatments. Thus, the needfor this scoping review on the management of prostate cancer in Africa.Aim: To give an account of the pattern of presentation, histological types,investigative and treatment modalities of prostate cancer in Africa. A literaturesearch through PubMed, Google Scholar, and African Journal Onlineon the management of prostate cancer in Africa was conducted. Results arethen reported according to the Preferred Reporting Items for SystematicReview and Meta-analyses extension for Scoping Review. Forty-three articlesfully satisfied the inclusion criteria and were used for this review.The commonest presentation of prostate cancer was lower urinarytract symptoms, followed by bone pain and urinary retention in that order.Adenocarcinoma was the commonest histological type for 98.5% of thestudy. A total 23.3% of patients had hormonal treatment which was the commonesttreatment option. Chemotherapy and open radical prostatectomywere used in 17.7 and 12.9% cases respectively. The use of robot-assistedradical prostatectomy was not an option of care noted in the review. Thefindings of this study highlight the need for integration of modern investigativemodalities and treatment options for prostate cancer in Africa.

Adherence to endocrine therapy with tamoxifen and satisfaction with follow-up of women with breast cancer by a gynecologist: A survey study

Background. Side effects of endocrine therapy with tamoxifen (TAM) reduce the quality of life of patients with breast cancer (BC) and adversely affect treatment compliance. Against the background of treatment of BC with TAM, the risk of developing endometrial hyperplasia (EH) increases. At the moment, algorithms for monitoring patients receiving TAM by an obstetrician-gynecologist have not been developed and approved. There are also divergent opinions of experts regarding the diagnosis and management of patients in the detection of EH. This article presents the results of the final stage of the study in 2017–2022 – a survey study. The purpose of this study was to assess adherence to endocrine therapy and satisfaction with observation by a gynecologist of women with BC after 5 years of observation and their relationship with the identified early associated polymorphisms of the CYP2D6, CYP3A5, CYP2C9 and ABCB1 genes. Materials and methods. 54 patients with BC, out of 120 who had previously passed the first pharmacogenetic stage of the study, were interviewed with specially designed questionnaire. Due to the small sample size, delta percentages (∆%) were used in each comparison group with a difference threshold of 5%. To assess associations with the studied genetic polymorphisms, previously obtained significant associations of adverse drug reactions with pharmacogenetics in the same patients were used. Results. The prevalence of all adverse drug reactions (ADRs), with the exception of EH, was higher in the group of patients who canceled TAM. Over 5 years of follow-up, 57.4% of patients were regularly observed by an obstetrician-gynecologist, 42.59% of patients visited a gynecologist less than once a year. Of all the respondents, 53.7% of patients are satisfied with the regularity and quality of dispensary observation by an oncologist, 33.33% of patients are satisfied with the regularity and quality of dispensary observation by an obstetrician-gynecologist. All studied ADRs (EH, hot flashes, asthenia, bone pain and dyspepsia) associated with various genetic polymorphisms, prevailed in the group of patients who stopped taking TAM due to drug intolerance (∆%: 25.72, 6.97, 4.81, 6.97 and 24.52 respectively) compared with the TAM-group. Conclusion. The results obtained confirm the role of the studied genetic polymorphisms in the development of ADRs of TAM, but only systemic (hot flashes, asthenia, bone pain and dyspepsia). With regard to endometrial hyperplasia, no significant differences were obtained, which requires more extensive studies.

Exercise in newly diagnosed patients with multiple myeloma: A randomized controlled trial of effects on physical function, physical activity, lean body mass, bone mineral density, pain, and quality of life.

Reduced physical function caused by bone destruction, pain, anemia, infections, and weight loss is common in multiple myeloma (MM). Myeloma bone disease challenges physical exercise. Knowledge on the effects and safety of physical exercise in newly diagnosed patients with MM is limited. In a randomized, controlled trial, we studied the effect of a 10-week individualized physical exercise program on physical function, physical activity, lean body mass (LBM), bone mineral density (BMD), quality of life (QoL), and pain in patients newly diagnosed with MM. Lytic bone disease was assessed, and exercise was adjusted accordingly. Primary outcome: knee extension strength. Secondary outcomes: Six-Minute-Walk-Test, 30-s Sit-to-Stand-Test (SST), grip strength, level of physical activity, LBM, BMD, QoL, and pain. Measurements were conducted pre- and post-intervention, and after 6 and 12 months. We included 100 patients, 86 were evaluable; 44 in the intervention group (IG) and 42 in the control group (CG). No statistically significant differences between groups were observed. Knee extension strength declined in the IG (p = .02). SST, aerobic capacity, and global QoL improved in both groups. Pain decreased consistently in the IG regardless of pain outcome. No significant safety concerns of physical exercise in newly diagnosed patients with MM were observed.

MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.

Bone cancer pain (BCP), due to cancer bone metastasis and bone destruction, is a common symptom of tumors, including breast, prostate, and lung tumors. Patients often experience severe pain without effective treatment. Here, using a mouse model of bone cancer, we report that MOTS-c, a novel mitochondrial-derived peptide, confers remarkable protection against cancer pain and bone destruction. Briefly, we find that the plasma level of endogenous MOTS-c is significantly lower in the BCP group than in the sham group. Accordingly, intraperitoneal administration of MOTS-c robustly attenuates bone cancer-induced pain. These effects are blocked by compound C, an AMPK inhibitor. Furthermore, MOTS-c treatment significantly enhances AMPKα 1/2 phosphorylation. Interestingly, mechanical studies indicate that at the spinal cord level, MOTS-c relieves pain by restoring mitochondrial biogenesis, suppressing microglial activation, and decreasing the production of inflammatory factors, which directly contribute to neuronal modulation. However, in the periphery, MOTS-c protects against local bone destruction by modulating osteoclast and immune cell function in the tumor microenvironment, providing long-term relief from cancer pain. Additionally, we find that chronic administration of MOTS-c has little effect on liver, renal, lipid or cardiac function in mice. In conclusion, MOTS-c improves BCP through peripheral and central synergistic effects on nociceptors, immune cells, and osteoclasts, providing a pharmacological and biological rationale for the development of mitochondrial peptide-based therapeutic agents for cancer-induced pain.

A Report of Pediatric Langerhans Cell Histiocytosis in a Hospital-Based Study

Background: The reports of Iranian Pediatric Langerhans Cell Histiocytosis (LCH) are rare and there is no specific survival rate for those cases. Objectives: This study was designed as a hospital-based project for evaluating the epidemiological data and survival rates of the mentioned patients. Methods: This was a cross-sectional descriptive study that enrolled patients younger than 15 years old with approved LCH malignancy. Data was gathered based on a unique questionnaire and analyzed by SPSS Software version 25. Results: There were 32 cases (male/female ratio = 0.88) who were categorized as high risk (n = 18), moderate (n = 9) and low risk (n = 5), respectively. The mean age of patients was 5.1 years and the common chief complaint in them was bone pain, with the skeleton site of involvement. The 5-years overall and event-free survival rates were 93.3% and 72.9%, respectively. Conclusions: The suggestion is to provide a national registry for pediatric LCH followed by designing future projects around affective genes on the treatment response of the mentioned patients. In that way, we can improve the survival rate of these patients and decrease mortality.

Primary hyperparathyroidism secondary to parathyroid carcinoma in a 53 year-old male presenting with lassitude, constipation and bone pains: a case report

Primary hyperparathyroidism secondary to parathyroid carcinoma in a 53 year-old male presenting with lassitude, constipation and bone pains: a case report

Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system

ABSTRACT Objective Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown. Methods The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed for the first quarter of 2019 through the second quarter of 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs). Results A total of 112 elagolix-induced AE signals were detected in 17 system organ classes (SOCs) that simultaneously met the thresholds of 4 algorithms. After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important adverse events that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. The majority of cases occurred within 1 month after initiation of elagolix treatment. Conclusion Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

Extraction and Analysis of Medicinal Property in Secondary Metabolites Obtained from Selected Plant Species

Medical plants have been used from thousands of years to treat and prevent many diseases. Wockhardt global school Consist various plants variety and for this study three medicinal plants were selected and these plants are Tridax procumbiens (Tantani), Ficus racemosa (Umbar), Nyctanthes abortiristis (Parijat). The primary aim of this study was to extract and identify the presence of phytochemicals and to determine their medicinal uses for human beings. From Vedic era the traditional plant medicines has been considered as a primary healthcare for human beings. In the given study the presence of flavonoids, alkaloids, N-Containing chemicals were determined by using phytochemical extraction method. The chemicals were identified based upon various qualitative tests. The selected plants consist glycosides, alkaloids, saponins, flavonoids and carbohydrates. This phytochemicals are responsible for anti-inflammatory properties hence the selected medicinal plants can be used for inflammation, bone pain, joint pain, swelling, and common cough etc. Keywords: Medicinal plants, secondary metabolites, phytochemicals, flavonoids, alkaloids, leaf extract.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score > 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-12.

Abstract PO5-12-06: Minimization of treatment toxicity/side effects and their impact on quality of life (QoL) in patients (pts) with ER+/HER2- metastatic breast cancer (mBC)

Abstract Introduction: Treatment toxicity and side effects may be underreported (Basu Roy. J Thorac Oncol 2018:13:1815-17) and can negatively impact QoL. As such toxicities can influence pts’ treatment decisions, we surveyed pts with ER+/HER2- mBC to better understand the impact and patient reporting accuracy of treatment toxicities/side effects. Methods: The EQUALS 3 (ESR1 QUAlity of Life Survey 3), 55-question survey was designed by the EQUALS Steering Committee, trialed by pt advocates, emailed to US subjects (Cure Media Group and authors’ contacts), and posted to private BC Facebook and Twitter groups for 2 wks in June 2023. Eligible pts had ER+/HER2- mBC and treatment changes due to disease progression. Pts received a $10 gift card at survey completion. Survey answers were descriptively summarized. Results: 213 pts completed the survey. Most were < 60 yrs of age (77%), White (44%) or Hispanic/Latino (48%), peri-/postmenopausal (54%), and college-educated (71%); had income >$50,000 (66%); lived in urban (51%)/rural areas (22%); and had therapy lines of 1st (8%), 2nd (36%), or 3rd+ (51%). Current mBC treatments were endocrine therapy (ET) ± targeted therapies (70%), antibody drug conjugate (8%), chemotherapy (11%), and other (10%). Most pts had a female oncologist (65%) who worked in an academic hospital (61%); 68% had >1 oncologist. Surveyed pts reported toxicity concerns for side effects ranging from serious to nuisance. Side effects most frequently reported as extremely/moderately concerning were respiratory symptoms (51%), blood clots in lungs (49%) or heart/brain (47%), cognitive dysfunction (47%), infections (46%), nausea/vomiting (44%), cardiac adverse effects (44%), diarrhea (42%), gait instability (41%), fatigue (39%), joint pain (39%), hair loss (33%), or sexual dysfunction (27%). Although 49% of pts felt comfortable speaking to their medical team (MT) about side effects, 62% reported having minimized side effects to their MT due to fears/concerns of being seen as a complainer (70%), dose reduction (66%), being taken off drug (65%), not accessing other drugs with similar toxicities (61%), reduced efficacy with lower dose (59%), or coming off trial (47%). Almost half (47%) did not report treatment side effects, mostly due to fear of being seen as a complainer (63%), being taken off drug (57%), reduced efficacy with lower dose (51%), dose reduction (50%), not accessing other drugs (50%), or coming off trial (41%). QoL was poor/very poor in 20% of pts and QoL was the most common (68%) important/very important factor for making a treatment decision based on risks. Most common side effects that negatively impacted QoL were sexual dysfunction (45%), joint pain (38%), vaginal atrophy/dryness (36%), fatigue (33%), bone pain (31%), and hair loss (26%). Toxicities/side effects also impacted pts’ anxiety (49%), career (46%), marriage (42%), finances (32%), housework (30%), and relationships (19%). Regret after taking a cancer medication due to side effects was reported by 46% of pts. Conclusion: In this survey of pts with ER+/HER2- mBC on ET predominantly, many treatment side effects caused concern, not necessarily related to their seriousness, and most pts had minimized or hid side effects at some point due to fear of negative perceptions from their MT, reduced treatment efficacy, or clinical trial changes. Although QoL was overall good for most, 20% had poor QoL (largely impacted by sexual dysfunction, joint pain, and vaginal issues). Regret about toxicities was also common and should be explored. Provider awareness of pts’ toxicity experience, fears, and impacts on daily lives opens the door for educational tools to improve MT communications for treatment decisions, informed consent, and more accurate toxicity reporting in clinical trials. Citation Format: Sarah Sammons, Jane Meisel, Kelly Shanahan, Timothy Pluard, Fumiko Chino, Dario Trapani, Dominic Carroll, Monica Kozlowski, Elizabeth Attias, Nicole Kuderer. Minimization of treatment toxicity/side effects and their impact on quality of life (QoL) in patients (pts) with ER+/HER2- metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-06.

Abstract PO2-05-02: Real-world experience of patients receiving treatment for hormone receptor-positive/human epidermal growth factor receptor-2 negative metastatic breast cancer: A global analysis of symptoms and side effects

Abstract Background: Advances in treatment for patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2–) metastatic breast cancer (mBC) have improved overall survival, but treatment resistance is common and median survival remains only a few years. These pts usually need chronic therapy and often experience symptoms and side effects. There is limited knowledge on pts’ experiences outside the clinical trial setting, largely because this information is not routinely reported. This analysis leverages a unique database of physician- and pt-reported data to describe symptoms and side effects among a real-world, geographically diverse population of pts receiving treatment for HR+/HER2– mBC. Methods: This retrospective cohort study used Adelphi Disease Specific Programme Real World Data, comprising validated, linked pt and physician questionnaire data from the US, France, Germany, Italy, Spain, and UK. Eligible pts were ≥18 y, currently receiving treatment for advanced BC and not enrolled in a clinical trial. Data were collected between August 2022 and February 2023. Physician surveys provided data on individual pt demographics and disease characteristics, comorbidities, treatment history, and treatment (including adherence). Physicians also reported presence or absence of symptoms and side effects after treatment initiation for each pt they considered. A subset of pts completed one-time validated quality of life (QOL) instruments, including the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-breast (BR23). Results: Data from 1578 pts receiving treatment for HR+/HER2– mBC were analyzed. Mean age was 65-y, 91% were white, 71% had de novo mBC, and 82% had ECOG performance status 0-1 at the start of current treatment. Across all lines of therapy, 71% of pts were receiving endocrine-based therapy, 16% were receiving chemotherapy only, and 13% were receiving other therapies; 40% of all pts were receiving second or later lines of any systemic therapy (2L+). Among all pts, the most common physician-reported symptoms and side effects (in ≥10% of pts) were bone pain (30%), change in appetite (13%), weight loss (12%), neutropenia (11%), and joint/muscle pain (11%). Pts on 2L+ therapy experienced a greater frequency of symptoms and side effects than those on first-line therapy (Table). Of 220 pts who completed QOL questionnaires, the most commonly reported symptoms and side effects (in ≥70% of pts) were feeling tired (87%), worry about future health (80%), general worrying (79%), needing to rest during the day (74%), feeling weak (74%), having trouble doing strenuous activity (71%), and trouble taking a long walk (71%). These were common irrespective of pt age, disease state (recurrent vs de novo), current treatment regimen, and line of therapy. Conclusions: This real-world analysis shows that both physicians and pts identified substantial symptoms and side effects during treatment. These were pervasive across the population and more common in those receiving 2L+ therapy, although it remains unclear which were due to treatment or disease. Thus, it is important to continue to develop treatments and supportive care to improve both clinical outcomes and pt QOL. Citation Format: MK Rehnquist, Ann Partridge, Annabel Lambert, Allison Kurian, Natalia Sadetsky, Emily Freeman, Lisa Carey. Real-world experience of patients receiving treatment for hormone receptor-positive/human epidermal growth factor receptor-2 negative metastatic breast cancer: A global analysis of symptoms and side effects [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-02.

Abstract PO1-12-07: Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis

Abstract Breast cancer is one of the most common cancers in women and is associated with poor outcomes due to the metastatic potential of high-grade tumors. One common site of breast cancer metastasis is to the bone, leading to serious adverse effects such as bone pain, bone fracture, and spinal cord compression. Denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b (RANK) ligand (RANKL), and Pamidronate, a bisphosphonate, are two pharmacologic agents offered for the treatment of these adverse complications. The goal of this study was to conduct a retrospective cohort analysis across multiple institutions to compare the efficacy of Denosumab vs. Pamidronate in the management of osteolytic bone metastases secondary to breast cancer by evaluating the risk of adverse events. TriNetX, an online network that provides access to anonymized medical records for more than 108 million patients in 72 large healthcare organizations, was used in this study. Two cohorts, consisting of 847 patients with a diagnosis of bone metastases and breast cancer, were created and subsequently matched for age, race, gender, and ethnicity. One cohort was given Denosumab while the other was given Pamidronate, and each cohort was excluded from receiving the other medication. The occurrence of pathologic fracture in each arm, spinal cord compression, and overall five-year survival rate was measured and analyzed. The results of this study showed that Denosumab had a statistically insignificant risk reduction in both pathological fracture (2.7% vs. 2.8%, p = 0.88) and spinal cord compression (2.6% vs. 2.7%, p = 0.88) and a statistically insignificant difference in the overall five-year survival rate (45.5% vs. 52.4%, p = 0.78) when compared to Pamidronate. As a result, additional factors such as financial cost, route of administration, dosing schedule, and potential adverse side effects should be discussed with each individual who requires pharmacological therapy for bone metastases secondary to breast cancer. Citation Format: Megan Bradley, Mabry Nichols, Brittany Miles. Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-07.

Influence of lithium ion doping and mitoxantrone hydrochloride loading on the structure and in vitro biological properties of mesoporous bioactive glass microspheres in the treatment of multiple myeloma

Multiple myeloma (MM) is an incurable plasma cell hematologic tumor in which bone pain is a typical symptom. The current main treatment methods not only easily cause multidrug resistance but also cause bacterial infections. Therefore, improving multidrug resistance and bacterial infection during MM therapy and repairing bone defects caused by bone pain are necessary. In this work, we propose a drug delivery platform of lithium-doped mesoporous bioactive glass microspheres (7Li-MBGs) with a mesoporous structure (2-5nm) and a high specific surface area (636 m2/g) to achieve these functions. Interestingly, lithium ions are network modifier doped into the silicon-oxygen network. This in turn affects the dissolution and release behavior of silicon ions in the MBGs network. Thus, the bioactive response as well as drug release of the MBGs were enhanced. During this process, hydroxyapatite easily forms on the surface, which has a therapeutic effect on bone defects caused by MM. The drug (mitoxantrone hydrochloride, MTO) release mechanism is diffusion-driven, suggesting that drug/platform interactions are key determinants of release kinetics and depend on the release medium environment and platform structure. In vitro antibacterial and cytotoxicity experiments proved that the synergistic effect of Li ions and the MTO improved the antibacterial ability of the MBGs (> 98%) and the ability to treat MM. Therefore, the proposed 7Li-MBGs drug delivery platform can effectively release drugs in the long-term, repair bone defects, inhibit bacterial growth and tumor cell activity, and provide new ideas for the treatment of MM.

Gaucher disease: About an observation

Introduction: Gaucher disease is an inherited lysosomal storage disorder caused by defective discomfort. The consequence is the deficiency or complete absence of an important enzyme, β-glucocerebrosidase, which controls specific metabolic processes in the body.Characterized by hematological, visceral and bone lesions and classified into 3 types. The main objective of our study is to describe the diagnostic peculiarity of our patient with Gaucher Disease. Patient and Method: We report the observation of a child 6 years and 3 months old, history of prematurity, from a non-consanguineous marriage and a twin pregnancy. Since the age of 5 years, she has had arthralgia, bone pain and prolonged fever and whose examination found slightly discolored conjunctiva, arthralgia of the generals and a discreet splenomegaly.Laboratory assessment objectified hypochromic microcytic iron anemia, CRP and elevated ESR and imaging found enlargement of the distal metaphyses of both femurs on femur radio, slight homogeneous splenomegaly on the abdominal echo and cervico-thoraco-abdomino-pelvic CT scan found focus of condensation; Hepato-splenomegaly with a spleen containing fine calcifications; Isolated left ureteral dilation; Inhomogeneous bone pattern. B-Glucocerebrosidasa demonstrated low activity and genetic testing report was not detected for any pathogenic mutations. Conclusion: If the symptoms of the disease are detected early and a correct diagnosis is made, organ damage can be prevented or mitigated by adequate treatment.

An assessment of the probability of patients experiencing bone pain for early prioritization to the rehabilitation clinic

Background: As a result of DEXA and risk factor-based evaluation, which rank patients according to their osteoporosis risk, risk assessment instruments such as the Osteoporosis Self-assessment Tool, Risk Assessment Instrument, and Simple Calculated Risk Estimation were created. Aims: In two phases, the precision of evaluation instruments will be assessed: pre-test, post-test, and pre-diagnostic DEXA will be utilised to determine the accuracy of the assessment tools and pre-test, respectively. Methods: From September to November 2021, this study examines osteoporosis patients at Prince Rashid bin Al-Hasan Military Hospital in Jordan. Bayes' theorem and osteoporosis screening methodologies are utilised to calculate the post-test probability of patients. Evaluation of AUROC and performance metrics will be conducted utilising a ROC curve. The term of the investigation is 2021-2021. Results: The gender distribution of the 206 patients examined in the study was 5.87:1. AUCs SEMs for the binary logistic regression models incorporating independent variables (OST, ORAI, and BAQ) varied in response to the probability of FRAX≥3% versus <3%. FRAX% exhibited the following sensitivity indices: 0.02, 75%, 41.36%, 66.36%, and 41.03%. The innovative quotient (BAQ), which represents the ratio of body weight to age, had respective pre-test probabilities of 0.789±0.033, 0.484±0.042, and 0.254±0.037. Conclusion: The research examined the probability of BLR_BAQ after the test was conducted using OST and ORAI references. Significant AUROCs were observed for all three osteoporosis instruments; however, the performance of the post-test probabilities for FRAX≥3% of the BLR_BAQ model was subpar, as evidenced by both the standards and ORAI inference.

Targeting TRPV4 Channels for Cancer Pain Relief.

Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels' involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics.

Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion.

Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking. Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls. Our study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells. We conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis.

The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05-0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01-0.11); Ward's triangle BMD increased 0.07 g/cm² (95% CI: 0.04-0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04-0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18-2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: -1.81-0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: -0.07; 95% CI: -1.12-1.25), serum calcium (MD: 0.01; 95% CI: -0.03-0.04), serum phosphorus (MD: 0.04; 95% CI: -0.03-0.10) and medication safety (OR: 1.75; 95% CI: 1.29-2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety.

P075 What has parenteral iron got to do with rheumatology?

Abstract Background/Aims A 39 year-old female had been experiencing a six-month history of insidious onset migratory joint and bone pain, stiffness, malaise and over the last four months proximal muscle weakness. There had been partial relief with the use of non-steroidal anti-inflammatory medication. Past medical history included severe menorrhagia secondary to fibroids with a haemoglobin of 50g/dl on a handful of occasions, requiring x3 iron infusions (Ferric Carboxymaltose (FCM)1000mg) over a two year period. The last two infusions were provided three months apart. After each infusion, profound fatigue ensued. A blood test demonstrated an elevated ALP 301 (RR 30-130 U/L), reduced phosphate 0.48 (RR 0.8-1.5mmol/L) and mildly reduced 25OH vitamin D 44 (RR 50-140nmol/L). Corrected calcium was low-normal 2.29 (RR 2.2-2.6mmol/L) as was PTH 4.62 (RR 1.6-6.9pmol/L). A CTCAP excluded malignancy. Methods The patient had been treated with Cholecalciferol 1000iu and Dipyridamole 100mg daily with weekly blood test monitoring for six weeks prior to review in the metabolic bone clinic. Dipyridamole aided biochemical and symptomatic improvement. Further tests returned with an elevated FGF23 252 (RR 0-100 RU/ml), a normal Urine phosphate/Creatinine 1.6 and TmP/GFR ratio (suggesting the FGF23 effect on the kidney was not severe or its effects inhibited by Dipyridamole). ALP had reduced slightly to 269, PTH was elevated at 10.81 (RR 1.95-8.49micromol/L) and 1,25 Dihydroxy Vit D 182 (RR43-144 pmol/L). Results The patient was diagnosed with Parenteral iron triggered hypophosphatemia osteomalacia (6H-syndrome). A delayed diagnosis and referral resulted from unfamiliarity of side-effects of parenteral iron, especially Ferric Carboxymaltose, which has an alert on the GOV.UK website. The patient discontinued IV iron and was placed on oral Ferrous Gluconate 300mg daily. In retrospect, bone and joint pain was likely the result of enthesial pain and pseudofractures. In patients with diagnostic uncertainty, an isotope bone scan would be beneficial in assessing the extent of such pseudofractures. Hypophosphatemia is common following FCM (≥1/100 to < 1/10), and often self-limiting and asymptomatic. However, sustained hypophosphatemia (from recurrent infusions) can result in osteomalacia. Both anaemia and certain iron preparations can cause an elevation in FGF23 leading to increased urinary phosphate excretion. Dipyridamole has anti-phosphaturic effects by inhibiting FGF23. Conclusion It is advised in such patients to monitor serum phosphate levels at two- and five-weeks post infusion and to re-evaluate therapy with FCM in patients with persistent hypophosphatemia. It is common for symptoms, imaging, and biochemistry (FGF23 and ALP) to remain elevated/positive several months after diagnosis. This case highlights the need to ask about iron infusions in the drug history in patients presenting with hypophosphatemia and to be aware that musculoskeletal pain following iron infusions can be a sign of osteomalacia which will need investigating. Rarely, proximal muscle weakness can occur following the above iron preparation. Disclosure K.M. Achilleos: None. V. Rajagopal: None. C. Adams: None. G. Clunie: None.

P019 Comparison of newly proposed chronic nonbacterial osteomyelitis classification criteria to previous diagnostic criteria

Abstract Background/Aims Chronic nonbacterial osteomyelitis (CNO) is an aseptic autoinflammatory bone disease of unknown etiology. This diagnosis can be delayed due to the non-specific nature of symptoms and normal imaging studies. New classification criteria were proposed in 2022. This study seeks to validate these new classification criteria by comparing them to previous diagnostic criteria in a cohort of known CNO patients. Methods This is a retrospective case-series of pediatric patients diagnosed with CNO (n = 39) between 2012 and 2023 in Virginia, USA. The newly proposed classification criteria (Table 1) was applied to this cohort. The entry criteria of chronic bone pain, age <18 years, abnormal radiograph and/or MRI were used prior to applying the newly proposed classification criteria. The 2008 Jansson diagnostic criteria and 2016 Bristol diagnostic criteria were also applied to the cohort for comparison and further validation. The clinical manifestations, laboratory results, and imaging studies that lead to a diagnosis of CNO were reviewed. Results The average age of diagnosis was 10 (range 2-17) years-old with the average time between onset of symptoms to confirmed clinical diagnosis being 24 (range 1-120) months. The most common presenting symptoms were bone pain (100%) and arthritis (49%). Evidence of radiographic abnormalities leading to CNO diagnosis was found with regional MRI (64%), bone scan (44%) with some requiring full body MRI (31%). Only one patient did not meet the new classification criteria (1/39; 3%) because of age <3 years, fever and elevated ESR which together gave less than the required 55 points for criteria fulfillment. One different patient (1/39; 3%) did not meet both the Bristol and Jansson criteria because of unifocal disease and lack of bone biopsy. Conclusion This retrospective chart review validates the newly proposed classification criteria for CNO. Older diagnostic criteria (Jansson and Bristol) both require advanced imaging and at times bone biopsy for fulfillment. We conclude that the newly proposed criteria is easy to apply even in the absence of a bone biopsy or advanced imaging studies. The newly proposed criteria will aid in the development of a homogeneous cohort for future studies about CNO. Disclosure A.M. Patel: Member of speakers’ bureau; ABBVIE, AMGEN, SANOFI. K.S. Lee: None. A.J. Kim: None.