Hematological Diseases and Osteoporosis.

Secondary osteoporosis is a common clinical problem faced by bone specialists, with a higher frequency in men than in women. One of several causes of secondary osteoporosis is hematological disease. There are numerous hematological diseases that can have a deleterious impact on bone health. In the literature, there is an abundance of evidence of bone involvement in patients affected by multiple myeloma, systemic mastocytosis, thalassemia, and hemophilia; some skeletal disorders are also reported in sickle cell disease. Recently, monoclonal gammopathy of undetermined significance appears to increase fracture risk, predominantly in male subjects. The pathogenetic mechanisms responsible for these bone loss effects have not yet been completely clarified. Many soluble factors, in particular cytokines that regulate bone metabolism, appear to play an important role. An integrated approach to these hematological diseases, with the help of a bone specialist, could reduce the bone fracture rate and improve the quality of life of these patients.

Therapeutic Options for the Management of Aromatase Inhibitor- Associated Bone Loss.

BACKGROUND: Breast cancer is the most commonly occurring cancer in women worldwide. Early breast cancer is a kind of invasive neoplasm that has not proliferated beyond the breast or the axillary lymph nodes. Current therapeutic strategies for breast cancer mainly include local therapies such as surgery or radiotherapy and systemic therapies like chemotherapy, endocrine, and targeted therapy. Nowadays, the adjuvant treatment for hormone receptor-positive early breast cancer in postmenopausal women remains the main effective systemic therapy which can improve disease- free survival and overall survival; it involves several endocrine treatment regimens, including Selective Estrogen Receptor Modulators (SERMs), Aromatase Inhibitors (AIs), or a combination of them. AIs have been shown to be more effective in preventing recurrence in postmenopausal women with early breast cancer when compared with tamoxifen, thus representing the standard of care for adjuvant endocrine therapy. Although AIs are usually well-tolerated, they can have some side effects. Apart from the appearance of arthralgias or myalgias and cardiovascular events, AI therapies, reducing already low endogenous postmenopausal estradiol levels, cause increased bone loss and increase fracture risk in postmenopausal women. OBJECTIVES: The objective of this review is to evaluate the therapeutic options in the management of Aromatase Inhibitor-Associated Bone Loss (AIBL). METHODS: We reviewed the current literature dealing with different therapeutic options in the treatment of AIBL. RESULTS: Clinical practice guidelines recommend a careful evaluation of skeletal health in all women with breast cancer before AI therapy initiation. Adequate calcium and vitamin D intake have also been suggested. Pharmacological attempts to minimize AI-related bone loss have focused on the use of antiresorptive agents, such as bisphosphonates and denosumab to protect bone integrity and reduce the risk of fractures. Furthermore, clinical trials have shown that by making the bone microenvironment less susceptible to breast cancer metastasis, these drugs are able to increase disease- free survival. CONCLUSIONS: AI, that are the pillar of the systemic treatment for patients with hormone receptorpositive breast cancer, are associated with different side effects, and in particular, osteoporosis and fractures. Both bisphosphonates and denosumab are able to prevent this negative effect.

Paget's Disease of Bone and Cardiovascular Risk: A Pilot Study.

BACKGROUND: The association between Paget's disease of bone (PDB) and increased cardiovascular (CV) risk has been suggested, but the literature is conflicting. OBJECTIVE: Our study aimed to evaluate two markers of CV risk, namely, common carotid artery intimamedia thickness (cIMT) and the aortic pulse wave velocity (PWV) in patients with PDB. METHODS: We enrolled 12 patients with PDB and 58 control subjects, matched for age. The diagnosis of PDB was based on clinical, radiological and biochemical parameters. RESULTS: Patients with PDB showed higher PWV values than the controls, whereas cIMT was slightly but not significantly increased. CONCLUSION: These findings, although limited by the small study population, represent an original observation that deserves further study. The higher arterial stiffness in PDB could be related to the increased bone turnover or the high levels of oxidative stress that characterize this population.

Familiar osteopoikilosis: Case report with differential diagnosis and review of the literature.

Osteopoikilosis (OP) is a rare autosomal dominant sclerosing bone disease, caused by heterozygous mutations in the LEMD3 gene. It is characterised by numerous focal lamellar bone compact deposits in the spongiosa. In this case report, we describe a famliar case of OP and review the literature.

Early vascular ageing biomarkers in osteoporotic outpatients: a pilot study.

Osteoporosis and atherosclerosis are significant public health problems that often coexist, especially in the elderly. Although some studies have reported an age-dependent relationship, others have suggested a causal relationship between osteoporosis and atherosclerosis. The aim of our study was to evaluate the cardiovascular risk in a population of patients with osteoporosis by measuring carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cf-PWV). A total of 58 patients with osteoporosis and an equal number of healthy control subjects were enrolled. All subjects underwent (1) a bone densitometry examination using dual X-ray absorptiometry, (2) a vascular evaluation for the measurements of cIMT and cf-PWV and (3) a blood sample for the evaluation of lipids and phosphocalcic metabolism. Patients with osteoporosis had a significant increase in cIMT and cf-PWV. There was also a significant inverse correlation between the femoral neck BMD and cf-PWV values. In conclusion, osteoporotic outpatients have earlier vascular ageing, with an increase of arterial stiffness. These data support a possible association between osteoporosis and atherosclerosis independent of age.

Pathogenesis of Thalassemia Major-associated Osteoporosis: A Review with Insights from Clinical Experience

Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and impaired remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective growth hormone-insulin-like growth factor-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The receptor activator of nuclear factor kappa-ß (RANK)/RANK ligand/osteoprotegerin and the Wnt/ß-catenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type 1 alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, thus the puzzle of the pathogenesis of TM-induced osteoporosis remains far from being solved.

A strange case of dyspnoea.

Acquired neuralgic amyotrophy, described for the first time by Parsonage and Turner, is a rare idiopathic disease that may occur in otherwise normal healthy individuals. It typically begins with sudden, unilateral shoulder pain that may also involve the neck and/or arm. Less frequently, the disease involves nerves other than those of the brachial plexus, such as phrenic nerves, resulting in dyspnoea. The diagnosis is based on the clinical presentation and is generally supported by electroneurography/electromyography. We report the case of a 45-year-old white man who was referred to our clinic for acute dyspnoea preceded by severe neck and right shoulder pain. Corticosteroid therapy ameliorated the clinical picture, but without a complete recovery.

Peripheral artery disease and osteoporosis: Not only age­related (Review).

Osteoporosis and atherosclerosis are two chronic degenerative diseases that share several biochemical pathways and risk factors. Previous studies have associated osteoporosis with carotid atherosclerosis, cardiovascular mortality and stroke, but data on the relationship with peripheral artery disease are few and conflicting. The OPG/RANK/RANKL system and Wnt/beta catenin signaling seem to be deeply involved in the pathogenesis of bone alterations and atherosclerotic processes also affect arteries of the lower extremities. Hypovitaminosis D could also play a role in the relationship of these two diseases. New and larger studies are necessary to shed light on this association and to design new drugs able to act in both these chronic degenerative diseases.

Sclerostin is a possible candidate marker of arterial stiffness: Results from a cohort study in Catania.

Osteoporosis and cardiovascular disease are worldwide public health issues. Recent evidence indicates a possible role of the canonical Wnt/ß-catenin signalling pathway as a common mediator between these two diseases. The aim of the present study was to investigate the relationship between serum concentrations of sclerostin and Dkk1, two extracellular inhibitors of Wnt/ß-catenin signalling, with carotid intima-media thickness (CIMT) and with arterial stiffness, evaluated by measuring the pulse wave velocity (PWV) in an ambulatory population of adults. To this aim, 67 subjects were recruited in the 'Atherosclerosis and osteoporosis: identification of common pathogenetic factors' investigation. Serum sclerostin levels correlated positively with CIMT (r=0.314, p=0.03) and inversely with the augmentation index, a marker of arterial stiffness (r=-0.286, p<0.05), whereas Dkk1 did not. Moreover, in a multivariate linear regression model, sclerostin [ß -0.1472; p=0.0023; standard error (SE)=0.04620] was an independent predictor of PWV in the study subjects. Our study shows that, following adjustment for confounders, sclerostin is an independent predictor of arterial stiffness in an ambulatory population, whereas Dkk1 is not.

The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus.

The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/ß-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of ß-catenin activity in the vascular cells.