Prevention Of Bone Complications Research Articles

Comparison of two parathyroid hormone (pth) assay methods in the monitoring of black african hemodialysis patients in the ivory coast (Maglumi® vs Vidas Biomerieux® Kits)

Parathyroid hormone (PTH) testing is recommended once or twice a year to prevent bone complications resulting from chronic kidney disease. However, its interpretation is subject to many factors, including the generation of the PTH test used. For this reason, it is recommended that each laboratory establish its own PTH Upper Limit of Normality (ULN). In order to guarantee optimal management of hemodialysis patients in the public sector in Côte d'Ivoire (West Africa), it proved important to compare the diagnosis of hyperparathyroidism made using two platforms used in the laboratory in charge of monitoring these patients: PTH VIDAS® (3rd Generation) and PTH MAGLUMI® (2nd Generation). This was a cross-sectional study of 65 haemodialysis patients in Abidjan. PTH determinations were performed simultaneously on VIDAS® and MAGLUMI® platforms. The results obtained were interpreted on the basis of PTH threshold values pre-established in the laboratory. 86.15% of patients had concordant diagnoses on both platforms, compared with 13.85% with discordant diagnoses. Statistical analysis of these results showed a non-statistically significant difference.: The limitation posed by differences in PTH concentration given by different platforms can be circumvented by using PTH ULN stablished for each platform for a given population. Conclusion: The diagnoses made by the two platforms are thus superimposable using their respective PTH ULN.

Assessment of Serum Minerals in Subclinical Hypothyroid and Overt Hypothyroid Patients.

BackgroundHypothyroidism, the commonest form of hormonal dysfunction, is due to thyroid hormone deficiency or its impaired activity. Homeostasis of the metabolism of minerals is regulated by thyroid hormones. If there is any disorder of the thyroid it will lead to disturbances of metabolism of minerals.AimTo study and compare serum calcium and serum phosphorus levels in patients of subclinical hypothyroidism and correlation of these parameters with thyroid-stimulating hormone (TSH) levels.Materials and methodsThis study included 70 patients with subclinical hypothyroidism, 70 patients with overt hypothyroidism, and 70 age- and sex-matched healthy controls. Thyroid profile (estimation of free triiodothyronine [FT3], free thyroxine [FT4], TSH) was done. In both cases and controls serum calcium and serum phosphorus levels were estimated.ResultsSerum calcium and phosphorus levels in patients of subclinical hypothyroidism was 8.75 ± 0.40 mg/dL and 3.80 ± 0.62 mg/dL, respectively. In patients with hypothyroidism it was 8.37 ± 0.52 mg/dL and 4.10 ± 0.75 mg/dL, respectively, and in controls it was 9.67 ± 0.97 mg/dL and 3.70 ± 0.71 mg/dL, respectively. Difference between these groups was statistically significant (p<0.05 ). Mean serum calcium and phosphorus for patients with TSH level <10 was 8.81 ± 0.33 mg/dL and 3.67 ± 0.60 mg/dL, respectively, and for TSH level >10 was 8.59 ± 0.51 mg/dL and 4.12 ± 0.54 mg/dL, respectively. The difference between both groups was statistically significant (p<0.05) for calcium, phosphorus .ConclusionsIn subclinical hypothyroidism serum calcium and serum phosphorus levels are significantly altered. Regular follow-up and estimating serum levels of these minerals in subclinical hypothyroidism patients should be done so it is beneficial to give mineral supplementations to prevent bone complications during the treatment of the disease.

Pancreatic Iron and Bone Health in Thalassemia Major

Background. It has been shown that serum ferritin and heart iron content are good indicators of bone mineral density (BMD) in patients with beta thalassemia major (TM). In the present study we explored for the first time the relationship between pancreatic iron and BMD and bone markers in TM.Methods. We considered 135 TM patients (68 M, mean age 37.79±7.74 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) Network. BMDs of the lumbar vertebrae (L1-L4) and femoral neck were measured by dual X-ray absorptiometry (DEXA) and were expressed as T-scores. Pancreatic iron overload was quantified by the T2* Magnetic Resonance Imaging (MRI) technique. Blood samples were collected for the measurement of bone formation markers (procollagen 1 amino-terminal propeptide-P1NP, osteocalcin and bone-specific-BAP alkaline phosphatise), bone resorption marker (carboxy-terminal telopeptide of type I collagen-CTX), calcium, and vitamin D.Results. Pancreatic T2* values were significantly associated to lumbar T-scores (R=0.207, P=0.017) as well as to femoral T-scores (R=0.242, P=0.005). The correlations remained significant also in patients without diabetes. Pancreatic iron (global pancreas T2*<26 ms) was detected in 8 patients. Patients with pancreatic iron showed significant lower lumbar T-scores (-2.61±0.89 vs -1.60±0.89; P=0.031) as well as femoral T-scores (-2.12±1.17 vs -1.03±0.97; P=0.009) and 7 of them (87.6%) had lumbar and femoral T-scores indicating osteopathy (osteopenia or osteoporosis).As regards as the markers, pancreatic T2* values were negatively correlated to BAP (R=-0.196 P=0.031) and positively correlated to vitamin D (R=0.220, P=0.014).Conclusion. A significant correlation, although not strong, was detected between pancreatic iron overload and bone disease. From a different point of view, our results support the role of endocrinopathies in thalassemic osteopathy and underline the critical role of a multi-disciplinary intervention in preventing bone complications. DisclosuresPepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

In silico exploration of binding of selected bisphosphonate derivatives to placental alkaline phosphatase via docking and molecular dynamics

Bisphosphonates constitute a group of pyrophosphate analogues therapeutically active against bone diseases. Numerous studies confirm their anticancer and antimetastatic potential as well as ability to relieve pathological pain. Although this is a known class of compounds, many aspects of their action remain unexplained and their new interaction partners are still being discovered. Due to the structural similarity to pyrophosphate, their interaction with pyrophosphate-recognizing enzymes seems to be feasible. In current work, the placental alkaline phosphatase (PLAP) is considered as a potential target for these class of compounds. PLAP is one of the enzymes responsible for degradation of pyrophosphate with high clinical significance. An elevation of PLAP level are considered as a potential cancer marker. An in silico study of complexes formed between selected phosphate derivatives and PLAP was performed. It indicates that all tested compounds: alendronic acid, clodronic acid, etidronic acid, zoledronic acid, imidodiphosphoric acid, pyrophosphoric acid, medronic acid, chloromethylenediphosphonic acid and hypophosphoric acid form a complexes with PLAP, stabilized by hydrogen bonds, hydrophobic and van der Waals interactions. Zoledronic acid, drug used in prevention of bone complications during cancer treatment was found to have the lowest estimated energy of binding (−6.6 kcal/mol). In silico study yielded very low energy of binding also for hypophosphate, equal −6.4 kcal/mol, despite having no identified hydrogen bonds. Subsequent molecular dynamic simulations, followed by molecular mechanics generalized-born surface area with pairwise decomposition calculations confirmed the stability of protein-ligand complexes. The results indicate that selected phosphate derivatives may potentially interact with the enzyme, changing its function, what should be investigated during in vitro studies.

Real-world use of denosumab and bisphosphonates in patients with solid tumours and bone metastases in Germany

PurposeBisphosphonates and denosumab prevent bone complications in patients with bone metastases from solid tumours. This retrospective, longitudinal, cohort study provides data on their real-world use in this setting in Germany.MethodsAdults with bone metastases from breast, prostate or lung cancer who were newly initiated on a bisphosphonate or denosumab between 1 July 2011 and 31 December 2015 were identified from a German healthcare insurance claims database. Primary outcomes included persistence, compliance, discontinuation and switch rates at 12 months.ResultsThis study included 1130 patients with bone metastases: 555 (49%) had breast cancer, 361 (32%) prostate cancer and 242 (21%) lung cancer. Mean age was 65 years for patients with breast or lung cancer and 74 years for those with prostate cancer. Across all tumour types, compared with any bisphosphonate, 12-month persistence was higher with denosumab (breast cancer 78% vs 54–58%, prostate cancer 58% vs 50%, lung cancer 68% vs 34–60%), median time to discontinuation was longer with denosumab and switch rates were lower for denosumab (breast cancer 5% vs 14–19%, prostate cancer 2% vs 11%, lung cancer 3% vs 7–12%). Compliance at 12 months was longer for denosumab than for any bisphosphonate in breast cancer (75% vs 42–48%) and in prostate cancer (47% vs 36%).ConclusionsPatients initiated on denosumab following a diagnosis of bone metastases from breast, prostate or lung cancer had greater medication persistence, longer time to discontinuation, improved compliance and lower switch rates than those initiated on a bisphosphonate.

HTLV-1 viral oncogene HBZ drives bone destruction in adult T cell leukemia.

Osteolytic bone lesions and hypercalcemia are common, serious complications in adult T cell leukemia/lymphoma (ATL), an aggressive T cell malignancy associated with human T cell leukemia virus type 1 (HTLV-1) infection. The HTLV-1 viral oncogene HBZ has been implicated in ATL tumorigenesis and bone loss. In this study, we evaluated the role of HBZ on ATL-associated bone destruction using HTLV-1 infection and disease progression mouse models. Humanized mice infected with HTLV-1 developed lymphoproliferative disease and continuous, progressive osteolytic bone lesions. HTLV-1 lacking HBZ displayed only modest delays to lymphoproliferative disease but significantly decreased disease-associated bone loss compared with HTLV-1-infected mice. Gene expression array of acute ATL patient samples demonstrated increased expression of RANKL, a critical regulator of osteoclasts. We found that HBZ regulated RANKL in a c-Fos-dependent manner. Treatment of HTLV-1-infected humanized mice with denosumab, a monoclonal antibody against human RANKL, alleviated bone loss. Using patient-derived xenografts from primary human ATL cells to induce lymphoproliferative disease, we also observed profound tumor-induced bone destruction and increased c-Fos and RANKL gene expression. Together, these data show the critical role of HBZ in driving ATL-associated bone loss through RANKL and identify denosumab as a potential treatment to prevent bone complications in ATL patients.

Cost-effectiveness of denosumab for the prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Aims: Bone complications (also known as skeletal-related events [SREs]) pose significant health and financial burdens on patients with bone metastases. Denosumab demonstrated superiority over zoledronic acid in delaying the time to first SRE. This study examined the lifetime cost-effectiveness of denosumab vs zoledronic acid from both US payer and societal perspectives.Methods: This analysis used a lifetime Markov model and included patients with breast cancer, prostate cancer, and other solid tumors and bone metastases. The societal perspective included direct medical, direct non-medical, and indirect costs associated with denosumab and zoledronic acid; the payer perspective included direct medical costs only. Bone complication rates for each tumor type were estimated from three pivotal phase 3 studies and modified to reflect real-world incidence.Results: From a societal perspective, compared with zoledronic acid, denosumab use resulted in an incremental cost of $9,043, an incremental benefit of 0.128 quality-adjusted life-years (QALYs), a lifetime cost per QALY of $70,730, and a net monetary benefit (NMB) of $10,135 in favor of denosumab. Direct drug costs for denosumab ($28,352) were higher than zoledronic acid/untreated ($578), but were offset by reduced costs associated with bone complications. From a payer perspective, denosumab use was associated with an incremental cost of $13,396, and an incremental benefit of 0.128 QALYs, for a cost of $104,778 per QALY and an NMB of $5,782 in favor of denosumab.Limitations: Some model inputs had limited information and, given that the results may be sensitive to changes in these inputs, our findings should be interpreted within the context of the data inputs and modeling assumptions used in the analysis.Conclusions: Denosumab is a cost-effective option to prevent bone complications in patients with solid tumors when considering both payer and broader societal perspectives.

Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.

Assessment of mineral status in subclinical hypothyroidism patients – A case control study

One of the important functions of thyroid hormones is homeostasis of mineral metabolism. So thyroid disorders usually lead to disturbances in mineral metabolism. Objective: To analyze serum levels of minerals like calcium, phosphorus and magnesium in patients of subclinical hypothyroidism and to correlate these parameters with TSH levels in cases. Materials and Methods: The study group included 70 patients who are diagnosed with subclinical hypothyroidism and 70 healthy controls who are age and sex matched with cases. Thyroid profile which includes estimation of serum T3, T4, TSH was done. Serum calcium, phosphorus and magnesium were also estimated in both cases and controls. Results: The study showed that in subclinical hypothyroidism patients serum calcium levels were significantly low with mean values of 8.9±0.62 and p Conclusion: The serum levels of minerals like calcium, phosphorus and magnesium levels are significantly altered in subclinical hypothyroidism. Frequent follow up and checking the levels of these minerals in SCH patients should be done. Along with the treatment of the disease, it is necessary to give mineral supplements to prevent bone complications. Keywords: Calcium, Phosphorus, Magnesium, Subclinical hypothyroidism, Thyroid stimulating hormone, Thyroid hormones.

Diagnosis of metastases in castration-resistant prostate cancer patients: Decision algorithm in imaging tests

IntroductionIn castration-resistant prostate cancer (CRPC), early detection of metastases is essential for the selection of treatment, and prevention of bone complications. However detecting incipient metastases remains a challenge as the conventional radiological tests (bone scintigraphy or computerised tomography) lack sufficient sensitivity. Diagnostic imaging techniques are currently available that have greater sensitivity and specificity, but are little used due to shortfalls in the recommendations. ObjectiveTo create an algorithm that indicates the most suitable diagnostic imaging techniques for the different M0 CRPC patient profiles based on the scientific evidence. Evidence acquisitionMeetings were held with eight experts in Urology, Pathological Anatomy, Radiodiagnostics and Nuclear Medicine organised by the Andalusian Association of Urology, in which the recommendations and scientific evidence on each of the diagnostic imaging techniques were reviewed. Summary of the evidenceWe present the current recommendations for the detection of metastasis in M0 CRPC patients, the patients that would benefit from early detection, and summarise the evidence to support the use of each of the new techniques. ConclusionsTechniques such as 18F-Choline PET/CT or DWWB MRI and probably open MRI have been demonstrated to have good sensitivity and specificity for patients with low PSA (<10ng/ml). Their inclusion in routine clinical practice will help improve the early detection of metastasis in CRPC patients.

Long Acting Zoledronic Acid Treatment for Vertebral Fracture Prevention in Multipl Myeloma Patients with Osteoporosis

BACKGROUND: Zoledronic acid (zoledronate) is the most commonly used bisphosphonate derivative for the prevention of bone related complications in patients with multiple myeloma. Monthly given and yearly given long acting zoledronate are two different forms of zoledronate. Monthly given zoledronate is the novel agent accepted as the standard treatment for the prevention of multiple myeloma bone related complications. Yearly given long acting zoledronate has no data on the use of multiple myeloma bone disease prevention. AIM:Our primary goal is investigating the vertebral fracture protective effects of a long acting zoledronat agent(Aclasta®) in multiple myeloma patients with associated osteoporosis .We choose vertebrae as the target because bones with the most frequent fractures in multiple myeloma are the vertebrae. As a secondary goal ;we planned to evaluate in preventing fracture development in other bones. METHODS:Patients diagnosed with active multiple myeloma in the Sanlıurfa Mehmet Akif Inan Education and Research Hospital Hematology Clinic at year 2017 were evaluated. Patients fulfilled the inclusion criteria(men and women over the age of 18 and newly diagnosed patients with multiple myeloma,who have lomber vertebra( L1-L4 total or L2-L4) or total femur or femur neck measurements of “(-)1 or lower of any of the T-values” by bone mineral densitometry). Five pa tients were identified who fulfilled these criteria. Four of the patients were female and one patient was male,the age range was between 42 and 76 years.All patients received weekly VCD (bortezomib 1.3 mg /m2 cyclophosphamide 500 mg ,dexamethasone 20 mg) intravenously.During the first administration of chemotherapy , long acting zoledronat (Aclasta®),5 mg was administered with a half-hour intravenous infusion . Simultaneously with the first administration of long acting zolendronat(Aclasta®),600 mg elemental calcium and 400 U vitamin D3 were administered daily to the patients. At the first evaluation time point ,sixth month of treatment beginning ,MRI evaluation of the vertebral column was planned to undergo for all five patients.At the same time patients were questioned for complaints consistent with bone fractures before each chemotherapy session and patients with suspected fracture are planned to be evaluated with MRI.RESULTS: All patients were in complete remission at the end of the induction treatment.Two of the patients had autologous stem cell transplants.One patient had a tooth extraction before autologous bone marrow transplantation.Any jaw complications did not develop in this patient.None of the five patients developed myeloma-related bone complications ,neither vertebral nor other bones, at the sixth month of therapy.No adverse effects(electrolyte disorders ,albuminuria,etc.) were observed in patients during the administration and follow up period of the drug.CONCLUSION: It is universaly recommended to apply zoledronate once a month for intravenously at least two years in patients with myeloma. Before every application serum creatinine, serum electrolytes, serum calcium levels and every 3 months albuminuria should be evaluated . Zoledronates have side effects such as fatigue (30%), low blood pressure (11%) and nausea (29%) .Every month we need blood testing to detect electrolyte abnormalities before the therapy and follow up albuminüria as possible side effects of the drug.There is a risk of exposure to side effects every month too.But most important point is ease of application and the cost. Monthly treatment's cost is 1080 USD with it's cheapest generic (U.S market price).When we compare monthly zoledronate with the application of yearly long-acting zoledronate , patients will not have to live all the above-mentioned side effects ,necessity of laboratory evaluation every month, and the cost is only 350 USD with cheapest generic(U.S market price).Long-acting zoledronate is more advantageous considering factors such as cost, ease of administration and frequency of side effects. What is missing here is the large clinical efficacy studies. Our study is first study in the literature and the result are not inconclusive because patient group is very small.But at the same time, we are thinking that long acting zoledronate is a promising agent for preventing bone complications in multiple myeloma patients.So we are planning a phase 3 study to reevaluate our proposal in a larger patient group. DisclosuresNo relevant conflicts of interest to declare.

Diagnóstico de metástasis en pacientes con cáncer de próstata resistente a la castración: algoritmo de decisión en pruebas de imagen

IntroductionIn castration-resistant prostate cancer (CRPC), early detection of metastases is essential for the selection of treatment, and prevention of bone complications. However detecting incipient metastases remains a challenge as the conventional radiological tests (bone scintigraphy or computerised tomography) lack sufficient sensitivity. Diagnostic imaging techniques are currently available that have greater sensitivity and specificity, but are little used due to shortfalls in the recommendations. ObjectiveTo create an algorithm that indicates the most suitable diagnostic imaging techniques for the different M0 CRPC patient profiles based on the scientific evidence. Evidence acquisitionMeetings were held with eight experts in Urology, Pathological Anatomy, Radiodiagnostics and Nuclear Medicine organised by the Andalusian Association of Urology, in which the recommendations and scientific evidence on each of the diagnostic imaging techniques were reviewed. Summary of the evidenceWe present the current recommendations for the detection of metastasis in M0 CRPC patients, the patients that would benefit from early detection, and summarise the evidence to support the use of each of the new techniques. ConclusionsTechniques such as 18F-Choline PET/CT or DWWB MRI and probably open MRI have been demonstrated to have good sensitivity and specificity for patients with low PSA (<10ng/ml). Their inclusion in routine clinical practice will help improve the early detection of metastasis in CRPC patients.

Radiothérapie conformationnelle des métastases osseuses vertébrales

Analgesic external beam radiation therapy is a standard of care for patients with uncomplicated painful bone metastases and/or prevention of bone complications. In case of fracture risk, radiation therapy is performed after surgery in a consolidation of an analgesic purpose and stabilizing osteosynthesis. Radiotherapy is mandatory after vertebroplasty or kyphoplasty. Spinal cord compression – the only emergency in radiation therapy – is indicated postoperatively either exclusively for non surgical indication. Analgesic re-irradiation is possible in the case of insufficient response or recurrent pain after radiotherapy. Metabolic radiation, bisphosphonates or denosumab do not dissuade external radiation therapy for pain relief. Systemic oncological treatments can be suspended with a period of wash out given the risk of radiosensitization or recall phenomenon. Better yet, the intensity modulated radiotherapy and stereotactic radiotherapy can be part of a curative strategy for oligometastatic patients and suggest new treatment prospects.

PREVENTION OF COMPLICATIONS IN CASTRATE-REFRACTORY PROSTATE CANCER PATIENTS WITH BONE METASTASES

Abstract: Prostate cancer (PC) is one of the most urgent problems in modern oncourology. Every year the world is recording more than 900 thousands new cases of prostate cancer. For this reason, the diagnosis and treatment of this disease has recently been given more attention, both abroad and in the Russian Federation. Despite improvements in diagnostic methods and implementation of programs for active detection of the disease in its early stages, the number of patients suffering from advanced forms of prostate cancer remains high. Currently, the main method of treatment in patients with metastatic prostate cancer remains the hormone therapy (HT). Patients with metastatic prostate cancer most frequently have localization of metastatic lesions in the lymph nodes and bones. Frequent localization of metastatic lesions in the bones is due to tumor cell tropism of prostate cancer to the bone. Metastatic bone disease, as well as long-term HT conducted in patients with metastatic prostate cancer, leads to irreversible disruption of bone remodeling, which may be accompanied by osteoporosis and fragility fractures. Bone metastases in patients with PC are the most common cause of complications and significantly impair the quality of life of patients. Therapy underlying the prevention of bone complications can be specific, aimed directly at the tumor tissue and non-specific, to strengthen bones and decrease its resorption processes. The article provides an overview of the literature covering the effectiveness of modern drugs, aimed at non-specific prevention of bone complications in patients with metastatic prostate cancer, such as bisphosphonates, and inhibitors of the ligand RANKL, as well as an overview of studies to assess the effectiveness of domestic analogue zolendronovoy acid preparation Resorba in the prevention of osteoporosis.

Prevalence of bone metastases and bone-targeting agent use among solid tumor patients in the United States.

PurposePatients with bone metastases are at an increased risk of experiencing morbidity due to bone complications, and bone-targeting agents (BTA) are indicated for the prevention of these complications. Population-based estimates of the prevalence of bone metastases associated with solid tumors, and current treatment patterns for these patients, are limited. This study was undertaken to estimate the prevalence of bone metastases from solid tumors and to describe recent trends in the use of BTA in the US.MethodsWe estimated the prevalence of bone metastases in the US in 2012 using data from Medicare fee-for-service and PharMetrics Plus, a large commercial claims database. We evaluated the proportion of patients with bone metastases who were treated with BTA in 2012, timing of initiation of BTA relative to bone metastasis diagnosis, and persistence on BTA, overall and by primary tumor type and treatment.ResultsThere were ~330,000 (168,063 Medicare fee-for-service; 162,239 other) patients aged ≥18 years living with solid tumors and bone metastases in 2012. BTA were used by 43% (Commercial) to 47% (Medicare) of patients in 2012, with the greatest use among breast cancer patients. Over half (Medicare: 57%; Commercial: 53%) of BTA-treated patients initiated BTA after experiencing a bone complication.ConclusionOf the estimated 330,000 solid tumor patients living with bone metastases in the US in 2012, many may have received less than optimal care to prevent bone complications during the calendar year.

Management of metastatic hormone-sensitive prostate cancer.

In 2014, prostate cancer will affect roughly 15% of American men during their lifetimes with about 230,000 new cases and 29,000 deaths per year. If required, most can be treated with curative surgery or radiotherapy. Upon relapse, androgen deprivation therapy (intermittent or continuous) is the cornerstone of treatment for hormone-sensitive disease. Response is variable and treatment is associated with a significant risk of toxicity. Recently, significant advances in survival have been demonstrated with chemohormonal therapy in men with high-volume disease. In addition, new findings have informed the approach to preventing bone complications in patients on therapy for metastatic hormone-sensitive prostate cancer. Devising clinical prediction tools and biomarkers is needed to select patients most likely to benefit from certain therapies and allow for a personalized approach.

A new emergency in oncology: Bone metastases in breast cancer patients (Review)

Breast cancer (BC) is the most common tumour in females and as a result, the management of such patients is a major public health issue. A high percentage of BC patients develop bone metastases (BMs), occasionally even several years following the initial diagnosis. BMs are responsible for high morbidity and a reduced quality of life with the onset of various clinical complications defined as skeletal-related events (SREs), including pathological fractures, spinal cord compression, hypercalcaemia, bone marrow infiltration and severe bone pain, requiring palliative radiotherapy. Such complications reduce functional independence and quality of life, decrease survival rates and increase healthcare costs. The current treatment for metastatic BC aims to achieve meaningful clinical responses, an improved quality of life, long-term remission, prolonged survival and in a small percentage of cases, a complete cure. The treatment of this malignancy has become progressively complex, including well-known antitumour agents or bone-targeted molecules aimed at preventing bone complications and improving patient quality of life and the treatment outcome of a multidisciplinary programme. The importance of a multi disciplinary approach in the management of BMs is also widely accepted. The major complication of BMs are SREs which are responsible for reducing prognoses and patient quality of life and are correlated with high rates of hospitalisation with the subsequent social and economic consequences. For these reasons, it is crucial to prevent where possible or to identify and treat SREs promptly in an attempt to mitigate the ever-increasing clinical and economic burden.

Preventing bone complications in prostate cancer

Bone metastases alone or in combination with androgen deprivation therapy-related bone loss places prostate cancer patients at greater risk for skeletal morbidities, including pain, pathologic fracture and spinal cord compression. These events significantly impair the patient's quality of life and place a significant burden on health-care resources. This review focuses on the management options for reducing skeletal morbidity in patients with prostate cancer, including life-style modifications, food supplementation, osteoclast-targeted therapy and selective estrogen-receptor modulators. The use of osteoclast-targeted therapy (denosumab and zoledronic acid) is supported by the strongest evidence and has been US Food and Drug Administration-approved for the treatment of patients with PCa at high risk of osteoporotic fractures and for the reduction of the risk of skeletal-related events in patients with castration-resistant prostate cancer. Ongoing trials are studying the potential role of osteoclast-targeted therapy in other settings throughout the course of the disease.

Bone disease in adult patients with β-thalassaemia major: a case–control study

Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case-control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with β-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients.

Preventing Bone Complications in Advanced Prostate Cancer

The diagnosis and treatment of prostate cancer have steadily been improving since the late 1980s. However, clinicians still confront a large group of men developing disease metastatic to bone. Adequate control of bone complications plays a fundamental role in achieving control of symptoms and quality of life in this group. Androgen deprivation therapy, the standard treatment for advanced prostate cancer, increases the risk of various complications, including bone disease. This review addresses the prevention of bone complications related not only to prostate cancer metastases but also to impaired bone integrity caused by androgen deprivation therapy.