Is the trabecular bone score useful for assessing bone quality in patients with axial spondyloarthritis and syndesmophytes? / ¿Es útil la puntuación de hueso trabecular en la valoración de la calidad ósea en pacientes con espondiloartritis axial y sindesmofitos?

INTRODUCTION AND OBJECTIVES: Syndesmophytes appear to falsely raise lumbar bone mineral density values, thereby hindering the diagnosis of osteoporosis by dual-energy X-ray absorptiometry in patients with axial spondyloarthritis. The objective of the study was therefore to analyse the influence of syndesmophytes at the lumbar level on trabecular bone scores and lumbar and femoral neck bone mineral density values and to assess the clinical and analytical factors associated with trabecular bone scores in axial spondyloarthritis. MATERIAL AND METHODS: From January 2017 to June 2018, a cross-sectional study consecutively included patients with axial spondyloarthritis according to Assessment in Ankylosing Spondylitis criteria. We assessed the trabecular bone scores and bone mineral density values and recorded clinical, demographic, disease-related and laboratory variables. RESULTS: The study included 82 patients with axial spondyloarthritis (38 with syndesmophytes and 44 without syndesmophytes). The mean age of the patients with and without syndesmophytes was 55.7±10.27years and 44.36±11.85years, respectively (P<.001). The mean trabecular bone score for the patients with and without syndesmophytes was 1.345±0.14 and 1.41±0.11, respectively (p < 0.05). There was an association between higher body mass index, erythrocyte sedimentation rate, disease duration and the number of levels affected by syndesmophytes and a greater risk of fracture as measured by the trabecular bone score. CONCLUSION: Trabecular bone scores do not appear to be masked by the presence of syndesmophytes.

Calcium and phosphorus metabolism and lithogenic factors in patients with osteoporotic fracture.

OBJECTIVES: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones MATERIAL AND METHODS: 67 patients with osteoporotic fractures surgically treated in trauma service are included. The area of the fracture site, fracture mechanism and the presence of osteoporosis were the factors taken into account to diagnose osteoporotic fracture. Mineral metabolism, calciuria, oxaluria, uricosuria and citraturia in 24hours urine were analyzed. The presence of abnormal calcium and phosphorus metabolism was proved comparing hypercalciuria patients with normocalciuria ones. RESULTS: 12 men and 55 women with mean age 68.8±14.5 years old were included. Mean Body Mass Index (BMI) was 27.4±4.1kg/m2. 42% of patients showed hypercalciuria, 34% hyperoxaluria, 34% hypocitraturia and 7% hyperuricosuria. Statistically significant differences were observed only in fasting calcium/creatinine ratio (0.17 vs. 0.08; P<.0001) when comparing patients with hypercalciuria with those with normocalciuria. CONCLUSIONS: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions.

How to prevent and treat pharmacological hypoglycemias.

A 58 year-old woman with type 2 diabetes diagnosed 3 years before came to our clinic. Her treatment was metformin 850 mg every 12 hours and glimepiride 4 mg every 24 hours. After the initiation of glimepiride 9 months before her weight has increased 5 kg, and she suffers frequent hypoglycemias which have affected her while driving. Her BMI is 35.5 kg/m². She has a normal eye fund exam. She has hypertension treated with telmisartán and hidroclorotiazide with adequate control, and also hypercholesterolemia treated with atorvastatine 40 mg every 24 hours. Her blood test shows an HbA1c of 7.0%, normal values of microalbuminuria, total cholesterol 149 mg/dl, HDL cholesterol 52 mg/dl, LDL cholesterol 98 mg/dl and triglycerides 123 mg/dl. Her blood pressure is 129/81 mmHg, there was no orthostatic hypotension, and her peripheral neurological examination shows normal results. In summary, our case is a young woman with type 2 diabetes and obesity, without chronic complications and which has frequent hypoglycaemia. How must this woman be evaluated and treated?

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

UNLABELLED: The 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. INTRODUCTION: Recent 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. METHODS: We 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. RESULTS: Serum 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 64.52 ± 27.21 pmol/L, non-ADT 48.24 ± 15.93 pmol/L, healthy controls 38.48 ± 9.19 pmol/L, p < 0.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: r = -0.309, p = 0.029; bioavailable testosterone: r = -0.280, p = 0.049; free testosterone: r = -0.299, p = 0.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group. CONCLUSIONS: Circulating 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.

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

SUMMARY: Fractures 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. INTRODUCTION: Fractures 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. METHODS: This is a cross-sectional study including 91 subjects with prostate cancer (54 % 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. RESULTS: SHBG levels were inversely related to BMD (femoral neck: r = -0.299, p = 0.00; total hip: r = -0.259, p = 0.019). Subjects with osteoporosis had higher SHBG concentrations than patients without osteoporosis (60.97 ± 39.56 vs 44.45 ± 23.32 nmol/l, p = 0.022). Patients with SHBG levels in the first quartile (>57.6 nmol/l) had an odds ratio (OR) for osteoporosis of 2.59 (95 % CI, 1.30-5.12; p = 0.009) compared with patients with lower SHBG levels. In patients with SHBG >57.6 nmol/l, the OR for vertebral fractures was 2.34 (95 % CI, 1.15-4.78; p = 0.034). The calculated OR was higher after adjustment for age (OR, 5.16; 95 % CI, 1.09-24.49; p = 0.039), estrogens (OR, 6.45; 95 % CI, 1.44-28.95; p = 0.023), and androgens (OR, 5.51; 95 % CI, 1.36-22.37; p = 0.017). CONCLUSIONS: In 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.

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.

Diabetes and osteoporosis: Action of gastrointestinal hormones on the bone. / Diabetes y osteoporosis: acción de las hormonas gastrointestinales sobre el hueso.

A 62-year-old woman consulted for evaluation of treatment for her type 2 diabetes diagnosed four years ago. He had been received treatment with metformin 850mg twice, with no chronic associated complications. She had hypertension and dyslipidemia. She was being treated with candesartan/hydrochlorothiazide 32/12.5mg and atorvastatin 40mg. Her weight was 92kg and height 162cm (BMI, 35.1kg/m(2)). The last analysis showed fasting glucose 168mg/dl and glycated hemoglobin 7.5%, Microalbuminuria was negative. Blood pressure and lipid profile were within the therapeutic range. Two years ago she suffered a nontraumatic Colle's fracture in her left arm for which she was taking a daily calcium and vitamin D supplement and weekly alendronate. In summary, this is an obese female patient with type 2 diabetes mellitus and inadequate metabolic control, She also has a history of fragility fracture. How should this patient be evaluated and treated?

[Cardiovascular disease, osteoporosis and risk of fracture]. / Enfermedad cardiovascular, osteoporosis y riesgo de fractura.

A 60-year-old man, who did administrative work, consulted for evaluation of the presence of osteoporosis. He smoked ten cigarettes a day and drank alcohol occasionally. Eight years ago he suffered a Colle's fracture in his right arm after an incidental fall, which resolved without complications. His mother had a hip fracture when she was 78 years old. The patient weighed 89.4 kg and his height was 165 cm (BMI 38 kg/m(2)). The DXA showed a T-score -2.4 at lumbar spine and -1.9 at femoral neck. He had suffered a myocardial infarction one year ago and is presently taking statin, a beta-blocker and enalapril. In summary, this is a male with a background of fracture due to fragility, with lumbar BMD close to those established as diagnostic of osteoporosis and he also has cardiovascular disease. How should this patient be evaluated and treated?

Relationship between serum levels of osteocalcin and atherosclerotic disease in type 2 diabetes.

AIMS: To analyze the relationship between serum levels of osteocalcin and parameters of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study of 78 patients with T2DM evaluated intima-media thickness, and the prevalence of coronary heart disease, atherosclerotic plaques and aortic calcifications. Serum osteocalcin levels were also determined by radioimmunoassay. RESULTS: The patients' mean age was 57.8±6.4 years (duration of diabetes: 13.4 years; mean HbA(1c) level: 8.01%), and 37.2% had coronary heart disease, 56% had an abnormal intima-media thickness, 26.9% had carotid plaques and 32.1% had aortic calcifications. Coronary heart disease was associated with higher levels of osteocalcin in male vs female patients (1.95±1.36 vs 0.93±0.86 ng/mL, respectively; P=0.006). Also, higher concentrations of osteocalcin were found in female patients with vs without abnormal intima-media thicknesses (2.17±1.84 vs 1.25±0.67 ng/mL, respectively; P=0.042), carotid plaques (2.86±2.10 vs 1.43±1.09 ng/mL, respectively; P=0.03) and aortic calcifications (2.85±1.97 vs 1.26±0.83 ng/mL, respectively; P=0.002). Serum osteocalcin levels were associated with coronary heart disease on multivariate logistic regression (odds ratio: 2.27, 95% confidence interval: 1.21-4.25; P=0.01). CONCLUSION: In T2DM patients, serum osteocalcin levels were associated with parameters of atherosclerosis, suggesting that osteocalcin is involved not only in bone metabolism, but also in atherosclerotic disease.

Results from a national survey on the management of primary hyperparathyroidism.

BACKGROUND: Management of primary hyperparathyroidism (PHPT) continues to be challenging. At the Third International Workshop on PHPT, recent data on this disease were reviewed and new clinical recommendations were developed. There are few data on the influence of new guidelines in clinical practice. AIM: We designed an online survey that was sent to all Spanish hospital endocrinology services. METHODS: The questionnaire included 28 questions about diagnosis and management of PHPT. Ninety-nine of 131 sites (76%), giving health coverage to 70% of Spanish population, completed the survey. RESULTS: The reported incidence of PHPT was 9.95/100,000 person-years. Heighty percent of patients were asymptomatic. Each center performed a median (Q1, Q3) of 12 (6, 20) parathyroidectomies/year. The median (Q1, Q3) percentage of curative interventions (at first trial) was 90% (80, 95). The main reasons for not performing surgery were, by decreasing frequency: surgery contraindication, patient's refusal, loss of monitoring, limited surgery experience. Localization techniques were used in 83% of cases. The main criteria for parathyroidectomy in asymptomatic patients were Ca≥2.875 mmol/l (79%), Tscore ≤-2.5 SD at any site (91%), age <50 yr (80%) and glomerular filtration rate <60 ml/min/1.73 m 2 (82%). Minimally invasive surgery was performed in 42% of centers. Frequency of biochemistry and bone density determinations for non-surgically managed patients was in accordance with international guidelines. CONCLUSIONS: The clinical practice of Spanish endocrinologists is consistent with the recommendations of the guidelines from the Third International Workshop for the management of PHPT.

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

Large-scale ELISA testing of Spanish red deer for paratuberculosis.

A role of wildlife species as paratuberculosis reservoirs is strongly suspected based on field and molecular epidemiologic evidence. This paper presents the first large-scale data on enzyme-linked immunosorbent assay (ELISA) against Mycobacterium avium subspecies paratuberculosis (MAP) antibodies in red deer from Spain, and tests the effect of host and environmental risk factors on antibody levels. A total of 257 out of 852 serum samples tested positive, yielding a total seroprevalence of 30.16% (95% CI 27.08-33.24). Sampling locality, presence of cattle and increasing age explained the variation in the individual ELISA optical density (OD) results. Data presented in this study strongly suggest that Spanish red deer are exposed to MAP. While contact with cattle was statistically significant, some wild populations showed the highest positivity to the ELISA. The results support the need of a careful study of MAP prevalence based on culture and molecular tools in order to clarify if deer play a significant role as paratuberculosis reservoirs for livestock, and if deer paratuberculosis is affecting hunting harvest, trophy quality, or wild animal welfare in Spain.