Bone Metastases In Cancer Patients Research Articles

Revealing the therapeutic potential of teriparatide: a review

Teriparatide is an FDA-approved medication for osteoporosis that presents promising results in treating various musculoskeletal conditions. It helps in improving the bone mineral density and preventing fractures in individuals with osteoporosis. Its effectiveness in treating non-union and delayed union fractures, atypical femoral fractures, and spinal fusion procedures makes it valuable in improving bone healing and reducing complications. Teriparatide also improves bone density and strength in individuals with osteogenesis imperfecta, helps prevent and treat hypocalcaemia post-thyroidectomy, and helps in the management of hypoparathyroidism. In MRONJ, teriparatide improves lesion resolution and reduces bony defects. Furthermore, it potentially prevents bone metastasis in cancer patients without stimulating tumour growth. Nevertheless, teriparatide may cause short-term side effects like nausea and long-term concerns pertaining to the risk of osteosarcoma. Recent European alliance of associations for rheumatology guidelines have highlighted teriparatide's superior effectiveness in achieving bone mineral density thresholds and reducing fracture risks. Further clinical trials are necessary to determine optimal dosages and treatment durations of teriparatide. The off-label use of teriparatide should be considered only under the guidance of a healthcare professional when standard options are unavailable or inadequate.

Diffused Pulmonary Uptake of Tc-99m Methylene Diphosphonate Bone Scan in Patient with Prostate Cancer without Blood Test and Correlative/Cross-Sectional Imaging Abnormalities: A Case Report

Introduction: Bone scan using Tc-99m methylene diphosphonate (MDP) is a commonly used procedure for evaluating bone metastasis in cancer patients. Extra-osseous pulmonary uptake in bone scans is mostly an incidental finding and occurs in a multitude of disorders. Clinicians should be alert to any findings on clinical or complementary diagnostic tools. We presented a case of prostate cancer male patients who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan without any blood test and correlative/cross-sectional imaging abnormality Case Presentation: An 80-year-old male with adenocarcinoma of the prostate with a Gleason score of 6 (3+3). The PSA level was 0.009. The patient had a history of recurrent atrial fibrillation (AF), postural dizziness, HTN, Gout, and chronic renal failure, but all of these comorbidities were under control. The patient underwent a bone scan to annually check for the presence of bone metastases. Three hours after administering 740 MBq Tc-99m MDP intravenously. The reports didn’t show any increased uptake that would indicate metastases in the bones. Instead, diffuse bilateral pulmonary uptake and a mild increase in cardiac uptake were present. On the same day, a computed tomography (CT) scan of the thorax revealed 3 micro-nodules in the right upper lung that were described as benign lesions, and a chest X-ray confirmed normal results. The patient’s laboratory results were within normal range, and there were no clinical lung symptoms or complaints. Considering the patient history of persistent AF, chronic renal failure, and a complaint of postural dizziness, the bone scan finding may indicate involvement of amyloidosis. The relationship between amyloidosis and cancer was also widely noted. Conclusions: Tc-99m MDP may play a role in evaluating amyloidosis involvement in an uncommon place such as the lungs. Future research should focus on analyzing diagnostic options in the patient’s condition in this situation. Keywords: cancer, diffused pulmonary uptake, amyloidosis, bone scan

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate.

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or β--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.

Influence of Cholesterol on the Regulation of Osteoblast Function.

Bone is a dynamic tissue composed of cells, an extracellular matrix, and mineralized portion. Osteoblasts are responsible for proper bone formation and remodeling, and function. These processes are endergonic and require cellular energy in the form of adenosine triphosphate (ATP), which is derived from various sources such as glucose, fatty acids, and amino acids. However, other lipids such as cholesterol have also been found to play a critical role in bone homeostasis and can also contribute to the overall bioenergetic capacity of osteoblasts. In addition, several epidemiological studies have found a link between elevated cholesterol, cardiovascular disease, an enhanced risk of osteoporosis, and increased bone metastasis in cancer patients. This review focuses on how cholesterol, its derivatives, and cholesterol-lowering medications (statins) regulate osteoblast function and bone formation. It also highlights the molecular mechanisms underlying the cholesterol-osteoblast crosstalk.

TRPV1 in dorsal root ganglion contributed to bone cancer pain.

Tumor growth in situ or bone metastases in cancer patients all can induce bone cancer pain. It is frequently occurred in patients with breast, prostate, and lung cancer. Because of the lack of effective treatment, bone cancer pain causes depression, anxiety, fatigue, and sleep disturbances in cancer patients, disrupts the daily quality of life, and results in huge economic and psychological burden. Over the past years, transient receptor potential channels (TRPs), especially TRP vanilloid 1 (TRPV1) in dorsal root ganglion (DRG), have been considered to be involved in bone cancer pain. The characteristic of TRPV1 had been well studied. The mechanisms under TRPV1 regulation in DRG with bone cancer pain are complex, including inflammatory mediators, endogenous formaldehyde, and other mechanisms. In the present review, we summarize the role and potential mechanism of TRPV1 in DRG in bone cancer pain. As the primary sensory neurons, targeting the TRPV1 channel in DRG, might have fewer side effects than in central. We hope systematically understand of TRPV1 modulation in DRG will bring more effective strategy.

PSAT164 Incidence and Severity of Hypocalcemia in Association with Antiresorptive Therapy in Cancer Patients with Bone Metastasis: An Integrated Health Network Experience

Abstract Introduction Antiresorptive therapy (ArT) has been known to decrease the risk of skeletal-related events (SRE), such as bone pain and pathological fractures, in cancer patients with bone metastasis (BM). While beneficial, ArT may cause adverse effects in this population including hypocalcemia, which can be severe and life-threatening. We examined the incidence, severity, and risk factors for hypocalcemia associated with the use of ArT to treat BM in cancer patients. Methods We conducted a retrospective review of the electronic medical records of adult patients with advanced cancer complicated by BM who were treated at our institution between January 2016 and November 2020. Our primary aim was to compare the incidence and severity of hypocalcemia with the use of IV Zoledronic acid (ZA), a bisphosphonate, vs SQ Denosumab (DM), a RANKL inhibitor, to treat BM in cancer patients.Our secondary aim was to compare risk factors associated with severe hypocalcemia (defined as albumin-corrected serum calcium < 7 mg/dL). Inclusion criteria were patients aged 19-99 years with a history of cancer with known BM, who received either ZA or DM. Results We reviewed 860 EMRs of patients treated within the specified period. 392 patients met inclusion criteria, among them, 297 (76%) and 95 (24%) received DM and ZA, respectively. There were no between-group differences in age, ethnicity, or weight. The median patient age was 71 years (range: 27–96). There were, however, between-group differences in gender (p=0.01) and cancer diagnoses (p=0.03). Females comprised 53.9% of the DM group vs. 40% of the ZA group. The top three cancer diagnoses were (DM vs ZA groups): breast (40.1% vs 26.3%), prostate (25.9% vs 40%), and lung cancer (17.8% vs 15.8%). Overall incidence of hypocalcemia was 48.8% (n=144) and 45.3% (n= 43) with the use of DM and ZA, respectively (p=NS). Severe hypocalcemia was more frequently observed with the use of DM vs ZA (6.6% vs 1.1%, p <0.05). Median (IQR) corrected serum calcium concentration following ArT (when trending calcium for the individual patient) was 8.4 (7.9-8.8) and 8.6 (8.2-8.8) mg/dL for DM a ZA groups, respectively (p=0.1). There were no between-group differences in risk factors for hypocalcemia, such as renal function (eGFR), concentrations of 25-hydroxy vitamin D, albumin, phosphorus, magnesium, or TSH. However, there was a between-group difference in the concentration of alkaline phosphatase (median 83 vs 101 IU/L for DM vs ZA, p= 0.02). There were no between-group differences in the type of BM (osteolytic vs osteoblastic, p=0.9) Conclusion: Severe hypocalcemia was significantly more common with the use of DM compared to ZA for the treatment of BM in cancer patients treated at our institution. Our study was limited by its retrospective design and the between-group differences in gender distribution and cancer diagnoses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Non-cancer Causes of Death Following Initial Synchronous Bone Metastasis in Cancer Patients.

PurposeTo investigate the non-cancer causes of death (COD) in cancer patients with synchronous bone metastasis (BM) that is based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe retrospective cohort study included malignant cancer patients with synchronous BM diagnosed from 2010 to 2018 in the SEER database. The frequencies and proportion of non-cancer COD were calculated and analyzed in different genders, ages, and races subgroups.ResultsA total of 97,997 patients were deceased and included into the current study and 6,782 patients were died of non-cancer causes with a male predominance (N = 4,515, 66.6%). Around half of deaths (N = 3,254, 48.0%) occurred within 6 months after diagnosis while 721 patients were deceased after 3 years. Lung and bronchus cancer, prostate cancer, breast cancer, kidney and renal pelvis cancer, and liver cancer were proved to be the top five cancer types resulting in non-cancer caused death. Cardiovascular and cerebrovascular diseases were the leading non-cancer cause of death (N = 2,618), followed by COPD and associated conditions (N = 553) and septicemia, infectious and parasitic diseases (N = 544). Sub-analyses stratified by gender, age and race were performed and the similar results with slightly difference were observed.ConclusionsCardiovascular and cerebrovascular diseases were the main non-cancer cause of death in cancer patients with synchronous BM. Other non-cancer causes included COPD, septicemia, infectious and parasitic diseases, and so on. These findings should be considered by physicians. Physicians can counsel cancer patients with BM regarding survivorship with death causes screening and focus on prevention of non-cancer deaths.

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.Clinical trial registration: Not applicable.

68Ga-P15-041, A Novel Bone Imaging Agent for Diagnosis of Bone Metastases.

Objectives 68Ga-P15-041 (68Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer, which can be readily prepared by using a simple kit formulation and an in-house 68Ga/68Ge generator. The aim of this study is to assess the potential human application of 68Ga-P15-041 for clinical PET/CT imaging and to compare its efficacy to detect bone metastases of different cancers with 99mTc-MDP whole-body bone scintigraphy (WBBS).MethodsInitial kinetic study using Patlak analysis and parametric maps were performed in five histopathologically proven cancer patients (three males, two females) using 68Ga-P15-041 PET/CT scan only. Another group of 51 histopathologically proven cancer patients (22 males, 29 females) underwent both 99mTc-MDP WBBS and 68Ga-P15-041 PET/CT scans within a week, sequentially. Using either pathology examination or follow-up CT or MRI scans as the gold standard, the diagnostic efficacy and receiver operating characteristic curve (ROC) of the two methods in identifying bone metastases were compared (p <0.05, statistically significant).ResultsFifty-one patients were imaged, and 174 bone metastatic sites were identified. 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS detected 162 and 81 metastases, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS were 93.1% vs 81.8%, 89.8% vs 90.7%, 77.5% vs 69.2%, 97.2% vs 93.4% and 90.7% vs 88.4%, respectively. Our results showed that the mean of SUVmax was significantly higher in metastases than that in benign lesions, 15.1 ± 6.9 vs. 5.6 ± 1.3 (P <0.001). Using SUVmax = 7.6 as the cut-off value by PET/CT, it was possible to predict the occurrence of metastases (AUC = 0.976; P <0.001; 95% CI: 0.946–0.999). However, it was impossible to distinguish osteoblastic bone metastases from osteolytic bone lesions. Parametric maps based on Patlak analysis provided excellent images and highly valuable quantitative information.Conclusions 68Ga-P15-041 PET/CT, offering a rapid bone scan and high contrast images in minutes, is superior to the current method of choice in detecting bone metastases. It is reasonable to suggest that 68Ga-P15-041 PET/CT could become a valuable routine nuclear medicine procedure in providing excellent images for detecting bone metastases in cancer patients. 68Ga-P15-041 could become a valuable addition expanding the collection of 68Ga-based routine nuclear medicine procedures where 18F fluoride is not currently available.

Clinical impact of targeted single-photon emission computed tomography/computed tomography (SPECT/CT) bone scintigraphy on the assessment of bone metastasis in cancer patients.

We investigated the clinical impact of single-photon emission computed tomography/computed tomography (SPECT/CT) bone scintigraphy combined with 16-slice CT on metastatic workup and treatment planning in a large cancer patient series. Between January 2019 and January 2020, a total of 600 cancer patients were prospectively evaluated with whole-body planar bone scan (wbPBS) for staging or restaging purposes. 272/600 had equivocal lesions on wbPBS and 265/272 underwent additionally a targeted SPECT/CT bone scintigraphy on designated regions. Findings were classified as benign (score 1), metastatic (score 2) and inconclusive (score 3). Findings from SPECT/CT bone scintigraphy were compared with the results of wbPBS. A total of 668 lesions were considered as unclear οn wbPBS and were re-evaluated through targeted SPECT/CT bone scintigraphy. Definite diagnostic findings on SPECT/CT bone scintigraphy were obtained in 227/265 (85.7%) patients and in 592/668 (88.6%) lesions vs. 15.4% of wbPBS alone. On per-patient analyses, 38.9% of patients were considered definitely nonmetastatic and 46.8% as definitely metastatic. On per lesion analyses using SPECT/CT bone scintigraphy, corresponding diagnostic rates were 47.5 and 41.2%. Although the addition of SPECT/CT bone scintigraphy significantly reduced the rate of equivocal wbPBS results (83.1%), it failed to provide a conclusive diagnosis in a relatively small proportion of lesions 76/668 (11.4%) in 38 patients. SPECT/CT bone scintigraphy afforded a significant reduction of the number of patients with equivocal findings who needed further evaluation with other imaging modalities, preventing unnecessary delays in diagnosis and potential changes in disease staging and treatment planning. Moreover, SPECT/CT bone scintigraphy slightly increased diagnostic sensitivity.

Clinical value of dual-phase F-18 sodium fluoride PET/CT for diagnosing bone metastasis in cancer patients with solitary bone lesion.

The present study aimed to investigate whether dual-phase F-18 sodium-fluoride (NaF) positron emission tomography/computed tomography (PET/CT) could improve the diagnostic accuracy of detecting bone metastasis in cancer patients with a solitary bone lesion compared to conventional F-18 NaF PET/CT. We retrospectively enrolled 113 cancer patients who underwent dual-phase F-18 NaF PET/CT for the differential diagnosis of a solitary bone lesion seen on bone scintigraphy. According to the dual-phase PET/CT protocol, an early-phase scan was acquired immediately after radiotracer injection and a conventional F-18 NaF PET/CT scan was performed. The diagnostic abilities of the visual analysis of conventional and dual-phase PET/CT scans and two quantitative parameters (lesion-to-blood pool uptake ratio on early-phase scan and lesion-to-bone uptake ratio on conventional scan) for detecting bone metastasis were compared. The final diagnosis of bone metastasis was made by histopathological confirmation or follow-up imaging studies. A metastatic bone lesion was diagnosed in 28 patients (24.8%). The sensitivity, specificity, and accuracy were 100.0%, 70.6%, and 77.9%, respectively, for visual analysis of conventional F-18 NaF PET/CT, 92.9%, 42.4%, 54.9%, respectively, for lesion-to-bone uptake ratio, 96.4%, 88.2%, and 90.3%, respectively, for visual analysis of dual-phase PET/CT, and 92.9%, 81.2%, and 83.2%, respectively, for lesion-to-blood pool uptake ratio. Visual analysis of dual-phase PET/CT was shown to have the highest area under the receiver operating characteristic curve value (0.923; 95% CI, 0.858-0.965) among all parameters. Dual-phase F-18 NaF PET/CT showed a high diagnostic ability for detecting bone metastasis with improved specificity and accuracy compared to conventional F-18 NaF PET/CT in cancer patients. Dual-phase F-18 NaF PET/CT might help diagnose bone metastasis in patients with malignancies who were shown to have a solitary bone lesion on bone scintigraphy.

The rise of metastatic bone disease in Ireland.

To describe the expected rise of metastatic bone disease in Ireland, the relative primary types, and the locations of spread within the skeleton. This was a population-based epidemiological study using cancer registry data. We included patients with known metastatic cancer to bone, within 1year of the primary diagnosis, during the years 1994 to 2012 inclusive. Our main outcome measures were age-specific, gender-specific and age-standardised incidence rates of bone metastasis, primary types and metastatic location within the skeleton. There were 14,495 recognised cases of bone metastasis in Ireland, 1994-2012 inclusive. Cases consistently rose over the time period, with 108% case increase and 51% age-standardised incidence rise. Annual percentage change increased across both genders and over all age groups. Most of this rise was not due to demographic population change. Breast, prostate and lung accounted for the majority of primary types. GI cancers were the fourth most common primary type. There were proportional increases in breast and lung, with proportional decreases in prostate. The spine was the major metastatic site. Bone metastasis is a significant and rising healthcare concern in Ireland. This rise is disproportionate to demographic changes. Breast, prostate and lung cancers account for the majority. GI cancers are implicated in an unexpectedly high number of cases. Spine is the most common location of bony metastasis, especially at presentation. Prudent healthcare planning is necessitated to prepare for the growing consequences of bone metastasis in cancer patients.

Clinical-morphological and laboratory predictors of «superscan» scintigraphy phenomenon in prostate cancer

Introduction. Detection of bone metastases in cancer patients is of great importance in the choice of treatment tactics and assessment of the disease prognosis. The article discusses the «superscan» phenomenon on bone scintigraphy in detecting skeletal metastases in prostate cancer (PC) patients. When analyzing published reports, we found only one large prospective study and a few case report publications on the detection of «superscan» in patients with generalized skeletal involvement. The purpose of the study was to determine the laboratory and clinical morphological parameters associated with «superscan» scintigraphic phenomenon in patients with prostate cancer. Material and Methods . Of 2474 prostate cancer patients who underwent bone scintigraphy, 48 had the «superscan» phenomenon. Clinical, laboratory and morphological parameters were: age of the patients, tumor stage by TNM (7th edition, 2010), histological type of the tumor, Gleason index, prostate specific antigen (PSA) level, pain syndrome (on a 5-point verbal scale of pain estimates, 1982), the presence of castration-resistant prostate cancer, hemoglobin level and erythrocyte sedimentation rate (ESR). Results . The «superscan» phenomen was found to occur most often in prostate cancer patients aged 60-69 years. Stage III and IV tumors were detected in 97.9 % of cases, lymphatic invasion in 20.8 %, and visceral metastases in 12.5 %. In addition, the phenomenon was associated with high PSA levels (the mean PSA level was 100 ng/ml, range: 26-4957) and the presence of moderately and poorly differentiated (Gleason ≥7)) tumors. Chronic pain syndrome at the time of detection of «superscan» was observed in 47.9% of patients, castration resistance - in 16.6 %. The median hemoglobin level was 114 (75-139) g/l and ESR was 34 (14-62) mm/h. Conclusion . The most significant factors associated with the «superscan» scintigraphy phenomenon in prostate cancer patients were the primary tumor extension, high PSA level and low-grade tumors. New data on the association between the «superscan» phenomenon and the levels of hemoglobin and ESR have been obtained. Further studies on the relationship between the «superscan» phenomenon and pain syndrome and castration resistance are required.

Comparison of sublingual buprenorphine and intravenous morphine in reducing bone metastases associated pain in cancer patients.

Bone metastases is one of the most common causes of pain in cancer patients and have a significant effect on their quality of life. The most common symptom of bone metastases is pain that gradually develops. Morphine is used to relieve pain in these patients, but poorly accepted due to its adverse events. Therefore, the current study was aimed to compare the effect of sublingual buprenorphine, with certainly lower complications with morphine. Fourth patients were divided into 2 groups. In group A, metastatic cancer patients received 2.5 mg of intravenous morphine. Furthermore, in group B, sublingual tablet of buprenorphine (one-fourth of a 500 μg tablet) was administered sublingually. Pain was measured 15, 30, and 45 minutes after the onset of pain using visual analog scale ruler. Based on the obtained data, two groups A and B were compared using SPSS 23 software. There was a significant difference between the patient's pain intensity after 15 and 30 minutes from the onset of pain in both groups. Due to the fact that the duration of the effect of morphine is 3-4 hours and the duration of the effect of sublingual buprenorphine is 6-8 hours, morphine showed fast acting forms of opioids (P= 0.001). The required dose level on the first day was similar in both groups and there was no statistically significant difference between the two groups. While on the second and third days, the median dose in group A (morphine) was greater than group B (buprenorphine), indicating prolonged duration of action for buprenorphine compared with morphine, thus requiring lower subsequent doses. The results of this study suggested that sublingual buprenorphine is a higher effective drug compared to intravenous morphine during and after operation. With regard to easy and painless administration, it seems that its use can be useful in controlling pain due to bone metastases in cancer patients.

Identification and Characterization of Predictive Factors of Onset of Bone Metastases in Cancer Patients

Identification and Characterization of Predictive Factors of Onset of Bone Metastases in Cancer Patients

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ.

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials.

Multidisciplinary treatment of pain caused by bone metastases in cancer patients: two case reports

Over 50% patients with malignant neoplasms suffer pain. In Poland, about 200,000 people annually have to contend with this problem. It can arise from the prolonged lifespan of cancer patients, the development of iatrogenic pain syndromes, pain associated with cancer cachexia, or decreased efficacy of analgesics due to induced opioid tolerance. The commonly used term “cancer pain” actually refers to all types of pain. In order that each patient is optimally treated, it is necessary to identify the type and cause of their pain. One of the more difficult types of pain to treat is that due to bone metastases; with its inflammatory and neuropathic components. Every patient has the right to proper pain treatment, with the goal of achieving the maximum analgesic effect while minimizing any side effects.

Analysis of metastatic involvement in bone using anatomical and functional information from 18F-FDG PET/CT.

Although the overall incidence of bone metastasis is not known, over one-half of the people who die of cancer in the USA every year are thought to have bone involvement. In this study we have developed a method to quantify the metabolic and anatomic changes induced by different types of bone metastases in cancer patients using PET/CT images. Seventy-three cancer patients with no previous history of chemotherapy or radiotherapy who had definite bone metastases documented by PET/CT and other conventional modalities were selected for this study. PET and computed tomography (CT) images were resampled to the same pixel size. Thereafter, the bone structure was segmented using thresholding. The 50% of the maximum standardized uptake value within the bone mask was used to identify bone lesions in each slice. Using the final regions of interest defined at 70% of the maximum, the lesion characteristics including the mean Hounsfield Units were computed from the PET/CT images. The lesions were subjected to visual confirmation by an experienced physician who also categorized them on the basis of the appearances in CT as lytic, sclerotic, mixed, or no-change type. The lesion characteristics were compared using statistical methods. In all, 340 bony lesions in 73 patients with different cancer types were analyzed. The lesions were further categorized into four groups on the basis of their anatomical location. The spine hosts the largest number of lesions. The lumbar bones are the most preferential sites within the spine. Statistical comparison of CT values indicated that the difference between no-change and lytic types was significant. Uptake period did not seem to have a significant impact on no-change and sclerotic types. Quantitatively, maximum standardized uptake value for lytic, no change, mixed, and sclerotic lesions were 7.4, 6.1, 8.2, and 7.2, respectively. A quantitative method provides a convenient way that may serve as a useful tool in monitoring and assessing the response to therapy.

Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases.

Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients.

The effect of resistance training during radiotherapy on spinal bone metastases in cancer patients – A randomized trial

PurposeTo compare the effects of resistance training versus passive physical therapy on bone density in the metastatic bone during radiation therapy (RT) as combined treatment in patients with spinal bone metastases. Secondly, to quantify pathological fractures after combined treatment. Material and methodsIn this randomized trial, 60 patients were allocated from September 2011 until March 2013 into one of the two groups: resistance training (group A) or passive physical therapy (group B) with thirty patients in each group during RT. Bone density in metastatic and non-metastatic vertebral bone was assessed at baseline, 3 and 6months after RT. ResultsBone density in all metastases increased significantly by 28.3% (IQR 11.4–139.0) and 80.3% (IQR 32.6–250.6) after 3 and 6months in group A (both p<0.01). The bone density in group A was significantly increased compared to control group after 3 and 6months (both p<0.01, median 59.7; IQR 21.1–98.3 and median 62.9; IQR −9.7 to 161.7). The bone density data in group B showed no significant increase over the course of time (p=0.289, median 5.5, IQR 0.0–62.2 and p=0.057, median 52.1, IQR 0.0–162.7). 23.3% of the patients in group A and 30.0% of the patients in group B had pathological fractures, no fracture was assigned to intervention, and no difference between groups after 3 and 6months was observed (p=0.592 and p=0.604). ConclusionsOur trial demonstrated that resistance training concomitant to RT can improve bone density in spinal bone metastases. This combined treatment is effective, practicable, and without side effects for patients. Importantly, the pathological fracture rate in the intervention group was not increased. The results offer a rationale for future large controlled investigations to confirm these findings.Trial registration: Clinical trial identifier NCT01409720.