Mariela Varsavsky

Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids.

SummaryThe role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone.IntroductionRecent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism.MethodsWe performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients.ResultsSerum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52u2009±u200927.21xa0pmol/L, non-ADT 48.24u2009±u200915.93xa0pmol/L, healthy controls 38.48u2009±u20099.19xa0pmol/L, pu2009<u20090.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: ru2009=u2009−0.309, pu2009=u20090.029; bioavailable testosterone: ru2009=u2009−0.280, pu2009=u20090.049; free testosterone: ru2009=u2009−0.299, pu2009=u20090.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group.ConclusionsCirculating sclerostin levels are significantly increased in patients with PC and particularly in those receiving ADT. The inverse relationship between serum sclerostin and testosterone in these patients suggests that androgens are key regulators of bone metabolism in this population.

Serum osteoprotegerin: bone or cardiovascular marker in Type 2 diabetes males?

Background: The role of osteoprotegerin (OPG) as a marker of cardiovascular disease (CVD) in Type 2 diabetes (T2DM) is not well established. Moreover, the relationship between OPG, osteoporosis, and vertebral fractures in T2DM remains to be elucidated. Aim: To determine the role of serum OPG in the prediction of CVD and bone disease in T2DM males. Subjects and methods: Cross-sectional study with 68 males, 43 with T2DM and 25 subjects without diabetes. We measured: serum OPG by inmunoassay, the presence of CVD (coronary heart disease, cerebrovascular and peripheral artery disease), surrogate markers of CVD [intima-media thickness (IMT) and aortic calcification] and bone disease (bone mineral density and prevalent vertebral fractures). Results: OPG serum levels (in pmol/l) were significantly higher in T2DM males with abnormal IMT (5. 12±1. 59 vs 3. 76±1. 98), carotid plaque (5. 46±1. 67 vs 4. 20±1. 81), aortic calcification (5. 91±1. 39 vs 4. 07±1. 76), hypertension (5. 11 ±1. 86 vs 3. 81 ±1. 47), and peripheral artery disease (6. 24±1. 64 vs 4. 21 ±1. 63, p<0. 05 for all comparisons). In the logistic regression analysis (after adjustment for age and main cardiovascular risk factors), serum OPG (per 1 pmol/l increase in OPG) was associated with increased risk of abnormal IMT [odds ratio (OR) 1. 84, confidence interval (CI) 1. 21–2. 79, p=0. 004), carotid plaque (OR 1. 71, CI 1. 13–2. 58, p=0. 012), aortic calcification (OR 2. 21, CI 1. 27–3. 84, p=0. 05) and peripheral artery disease (OR 4. 02, CI 1. 65–9. 8 p=0. 002). However, OPG were not related to bone mass or vertebral fractures. Conclusions: Our results suggest that in T2DM males OPG serum concentrations constitute a marker of CVD, but not a marker of bone disease.

SHBG levels are associated with bone loss and vertebral fractures in patients with prostate cancer

SummaryFractures are increased among prostate cancer patients. No data have been reported in patients with prostate cancer about the relation between serum sex hormone-binding globulin (SHBG) and bone metabolism. We found that SHBG levels were inversely related to bone mass and vertebral fractures in this population.IntroductionFractures are increased among prostate cancer patients, especially those on androgen deprivation therapy (ADT), but few data are available on the role of SHBG in their bone status. Our objective was to analyze the relation between serum SHBG and bone metabolism in prostate cancer patients.MethodsThis is a cross-sectional study including 91 subjects with prostate cancer (54xa0% with ADT). We measured serum levels of SHBG and sex steroids, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and prevalent radiographic vertebral fractures.ResultsSHBG levels were inversely related to BMD (femoral neck: ru2009=u2009−0.299, pu2009=u20090.00; total hip: ru2009=u2009−0.259, pu2009=u20090.019). Subjects with osteoporosis had higher SHBG concentrations than patients without osteoporosis (60.97u2009±u200939.56 vs 44.45u2009±u200923.32xa0nmol/l, pu2009=u20090.022). Patients with SHBG levels in the first quartile (>57.6xa0nmol/l) had an odds ratio (OR) for osteoporosis of 2.59 (95xa0% CI, 1.30–5.12; pu2009=u20090.009) compared with patients with lower SHBG levels. In patients with SHBG >57.6xa0nmol/l, the OR for vertebral fractures was 2.34 (95xa0% CI, 1.15–4.78; pu2009=u20090.034). The calculated OR was higher after adjustment for age (OR, 5.16; 95xa0% CI, 1.09–24.49; pu2009=u20090.039), estrogens (OR, 6.45; 95xa0% CI, 1.44–28.95; pu2009=u20090.023), and androgens (OR, 5.51; 95xa0% CI, 1.36–22.37; pu2009=u20090.017).ConclusionsIn prostate cancer patients, SHBG levels were inversely related to bone mass and vertebral fractures. Determination of the serum SHBG level may constitute a useful and straightforward marker for predicting the severity of osteoporosis in these patients.

Documento de consenso de osteoporosis del varón

OBJECTIVEnTo provide practical recommendations to assess and treat osteoporosis in males.nnnPARTICIPANTSnMembers of the Bone Metabolism Working Group of the Spanish Society of Endocrinology.nnnMETHODSnRecommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in Medline (PubMed) using the following associated terms: «osteoporosis», «men», «fractures», «bone mineral density», «treatment», «hypogonadism», and «prostate cancer». Papers in English and Spanish with publication date before 30 August 2017 were included. Current evidence for each disease was reviewed by 2group members. Finally, recommendations were discussed in a meeting of the working group.nnnCONCLUSIONSnThe document provides evidence-based practical recommendations for diagnosis, assessment, and management of osteoporosis in men and special situations such as hypogonadism and prostate cancer.

Osteomalacia tumoral: un síndrome paraneoplásico emergente

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies.

Recomendaciones sobre el efecto de los fármacos antidiabéticos en el hueso

OBJECTIVEnTo provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture.nnnPARTICIPANTSnMembers of the Bone Metabolism Working Group of the Spanish Society of Endocrinology.nnnMETHODSnThe GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND osteoporosis, fractures, bone mineral density, bone markers, calciotropic hormones. Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group.nnnCONCLUSIONSnThe document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk.