GUIDELINES FOR THE PREVENTION, DETECTION AND THERAPY OF VITAMIN D DEFICIENCY IN ADULTS.

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin D.

Fragility spinal fractures among cirrhotic liver transplant candidates in Croatia.

INTRODUCTION: Existing data on fragility spinal fractures prevalence in liver transplant candidates are scarce and inconsistent. This may be due to other comorbidities, besides hepatic osteodystrophy (HO), that contribute to bone loss and fragility fracture prevalence in chronic liver disease (CLD). OBJECTIVES: The aim of this study was to investigate the prevalence of spinal thoracic and lumbar fragility fractures among cirrhotic, non-chronic kidney disease (CKD), non-diabetic liver transplant candidates and to explore their relationship with clinical characteristics, laboratory markers and dual-energy x-ray absorptiometry (DXA) results. MATERIAL AND METHODS: This cross-sectional observational study was conducted at Merkur University Hospital, Croatia, between February 2019 and May 2023. Adult patients with liver cirrhosis referred for liver transplantation were included. Patients with acute infection, CKD, diabetes mellitus, malignancies, inflammatory bone diseases and those on corticosteroid or antiresorptive therapy were excluded. Clinical, laboratory and radiological assessment was carried out and patients were accordingly allocated into non-fractured and fractured group for the purpose of statistical analysis. RESULTS: A total of 90 patients were included in the study. There was 123 fractures, 87 (70.7 %) in the thoracic and 36 (29.3 %) in the lumbar region. Eighty-nine (72.4 %) fractures were grade 1, 31 (25.2 %) were grade 2 and 3 (2.4 %) were grade 3. Patients in the fractured group were significantly older (p < 0.001). No significant differences between fractured and non-fractured group according to laboratory and DXA parameters were noted. Subgroup with lumbar fractures had significantly lower bone mineral density values at L1-L4 region. Statistically significant negative correlation between bone specific alkaline phosphatase (BALP) and hip total BMD (rho = -0.414, p < 0.001) and spine total BMD (rho = -0.258, p = 0.014) values was found. CONCLUSION: Present study confirmed detrimental impact of CLD and HO on bone strength. DXA measurement correlated with the presence of lumbar fragility fractures. A combination of standard X-ray imaging and DXA is needed for adequate bone evaluation in pretransplant period and BALP could be useful for detecting HO in CLD. Searching for other risk factors and implementing bone turnover markers and additional imaging techniques for bone loss evaluation in liver transplant candidates is needed.

Diet quality in elderly nursing home residents evaluated by Diet Quality Index Revised (DQI-R).

The objective of this research was to evaluate diet quality in elderly nursing home residents and to point out the critical dietary components. The participants (277 females and 62 males) were recruited from all elderly nursing homes in Zagreb and each of elderly nursing homes was equally represented in this study. The age of subjects was ranging from 61 to 93 years; most of the females (53.4%) and males (53.2%) were between 70 and 80 years old. The dietary data from the multi pass 24-hour recall were used to compute the Diet Quality Index Revised (DQI-R). DQI-R is an instrument that provides a summary assessment of a diet's overall healthfulness and is based on ten different aspects, including recommendations for both nutrient and food types. Pearson correlation analysis was used to compare the total DQI-R score with dietetic parameters and t-test was calculated between mean values of all the components of DQI-R as well as for total DQI-R score for men and women. The mean DQI-R score for the 339 sample was 62.1 +/- 11.7. The biggest number of participants satisfied recommendations about dietary cholesterol intake (88.5% of participants) and dietary moderation score (71.1% of participants) but nobody satisfied recommendation about dietary diversity score. Only 3.2% of subjects had an adequate calcium intake (6.5% of male participants and only 2.5% of female participants). Recommended servings of fruit intake were satisfied by 19.8% of population, 30.4% satisfied vegetables recommendations and 38.6% recommendations for grains. According to DQI-R, beside positive dietary habits regarding dietary moderation and dietary cholesterol intake the population of elderly nursing home residents in the capital of Croatia needs improvement in other dietary habits in order to enhance successful aging.

[Management of adrenal incidentaloma: the position statement of the Croatian referral center for adrenal gland disorders]. / Dijagnostika i lijecenje incidentaloma nadbubrezne zlijezde: preporuke referentnog centra ministarstva zdravstva za bolesti nadbubrezne zlijezde.

Adrenal incidentalomas are tumours of adrenal glands discovered during diagnostic workup for other clinical condition unrelated to adrenal glands. Improvement in imaging techniques and their widespread use in everyday practice have increased detection of adrenal incidentalomas making their management one of the most important challenges of modern endocrinology. Based on the relevant medical literature and guidelines of other international societies a panel of Croatian leading experts in adrenal gland disorders provide practical recommendations for the diagnostics and treatment of adrenal incidentaloma.

[Differences among bisfosfonates--specificity of risedronate (Actonel)]. / Razlike medu bisfosfonatima--specificnosti risedronata (Actonel).

Bisphosphonates, a gold standard in therapeutic options for the management of osteoporosis, inhibit bone resorption with relatively few side effects. As a result, they are widely used for the prevention and treatment of osteoporosis. There are clear biochemical and pharmacological differences among bisfosfonates group. Risedronate has moderate mineral binding and has a higher inhibition of a key branch-point enzyme famesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Risedronate (Actonel) prevents vertebral and nonvertebral fractures as early as at 6 months of treatment. Clinical trials and observational trials have proved risk reduction of vertebral and hip fractures. Patients remarkably preferred therapy with a proven antifracture efficacy over a dosage frequency.

The Possibility of Applying the Vitamin D Brief Food Frequency Questionnaire as a Tool for a Country with No Vitamin D Data in Food Composition Tables.

Although the role of vitamin D is well known, the possibility of assessing its intake may be constricted in countries with no vitamin D data in food composition tables, as in the case of Croatia. The aim of the presented study was to adjust the VIDEO-FFQ (Vitamin D Estimation Only-Food Frequency Questionnaire), previously validated in Poland, to the Croatian population and to assess the validity and reproducibility of the adjusted Cro-VIDEO-FFQ (Croatian-VIDEO-FFQ). The study involved a group of Croatian women aged 20⁻30 and the Polish questionnaire was adjusted for a population due to similarities of the nutritional habits between countries. 106 individuals were recruited and 63 completed all the stages of the study. Participants conducted a 3-day dietary record and filled out the Cro-VIDEO-FFQ1 (first stage), as well as the same questionnaire (Cro-VIDEO-FFQ2) 6 weeks after (second stage). The following vitamin D intakes were observed in the studied group: 1.9 µg (0.2⁻8.0 µg) for 3-day dietary record, 3.3 µg (1.1⁻10.6 µg) for Cro-VIDEO-FFQ1, 3.6 µg (1.4⁻7.8 µg) for Cro-VIDEO-FFQ2. The Bland-Altman indexes in assessment of validity and reproducibility were 4.8% and 6.3%, respectively, with mean differences of 0.55 µg and 0.12 µg, as well as limits of agreement -0.91⁻2.01 µg and -0.44⁻0.69 µg. The kappa coefficient indicated a fair agreement for validity (0.21) and substantial for reproducibility (0.62), while correlations were significant (p = 0.0027, r = 0.37 for validity; p < 0.0001, r = 0.80 for reproducibility). It was observed that VIDEO-FFQ may be adjusted as a simple tool to assess vitamin D intake in a population with no vitamin D data in food composition tables, while Cro-VIDEO-FFQ may be a valid tool for nutritional assessment in Croatia.

Bone properties in patients with acromegaly: quantitative ultrasound of the heel.

Growth hormone (GH) deficiency and acromegaly serve as good models for investigating the effects of GH on bone remodeling. However, the results from various studies are rather conflicting. The aim of our study was to estimate the potential role of gender, disease activity, and duration on both calcaneus quantitative ultrasound (QUS) parameters and bone turnover markers in patients with acromegaly. Thirty-six acromegalic patients (17 men, 19 women) and 3 age- and gender-adjusted controls for every patient were included in the study. The disease was active in 22 patients, and was considered cured in 14 of them. In each subject, QUS of the heel and parameters of bone turnover (bone alkaline phosphatase, beta-crosslaps, and osteocalcin) were measured. The results demonstrated lower QUS values in acromegalic patients compared with the controls. When stratified by gender, the differences in QUS parameters were significant in men, but not in women. Male patients with active disease had significantly lower QUS values than those in remission. Such differences were not observed among women. Multiple regression model indicated strong association between disease activity and the QUS parameters. The group of patients with active disease had a higher level of serum beta-crosslaps, whereas osteocalcin concentration was significantly increased only in male patients with active disease. The results of our study suggest significantly lower QUS values and increased bone turnover in male patients with active acromegaly. The disease activity is the strongest predictor of the QUS parameters in acromegalic patients.

The effects of the level of physical activity on calcaneal ultrasound measurements: bone properties of medical and physical education students.

The aim of the study was to compare bone properties of two groups of students which strongly differ in the level of their everyday physical activity; the School of Medicine (SM) students and the Faculty of Physical Education (FPE) students, University of Zagreb. Quantitative ultrasound parameters--broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured. Quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were calculated by the device software. The final study sample consisted of 165 students from SM (94 males and 71 females) and 215 students from the FPE (164 males, 51 females). Sixty eight percent of FPE students and 21% of SM students reported a high level of everyday physical activity (P < 0.001). All ultrasound parameters were significantly higher in FPE students than in SM students (at the P < 0.001 level). The multiple regression model of the QUI confirmed that the school students attended was the single significant predictor variable for both genders. Our data indirectly showed the beneficial role of physical activity on bone properties.

[Treatment of osteoporosis]. / Lijecenje osteoporoze.

Osteoporosis is among the most frequent metabolic diseases affecting 8% to 10% of the population. Since the most disturbing outcome of osteoporosis is a fracture, it is important to identify patients at risk and intervene with pharmacologic therapies and lifestyle changes. Several drugs have shown their ability to reduce vertebral and/or peripheral fractures in patients with osteoporosis. Antiresorptive agents are a basis of therapy, but anabolic drugs have recently widened therapeutic options. Antiresorptive medications, estrogens, selective estrogen receptor modulators, bisphosphonates and calcitonins, work by reducing the rates of bone remodeling. Parathyroid hormone stimulates new bone formation, repairing architectural defects and improving bone density. Strontium ranelate reduces the risk for osteoporotic fractures by both inhibiting bone resorption and increasing bone formation. Other potential therapies for osteoporosis are also reviewed in this article.

[Osteoporosis prevalence in Croatian males--the results of calcaneus ultrasound]. / Ucestalost osteoporoze u muskaraca u hrvatskoj--rezultati ultrazvucne denzitometrije petne kosti.

The aim of the study was to establish the normative QUS data in a healthy sample of Croatian males and estimate the prevalence of osteoporosis. A total of 1002 male participants, aged 20-99, were recruited in seven study centers (Zagreb, Ivanic-grad, Koprivnica, Sibenik, Pula, Slavonski Brod, Vukovar). In each subject broadband ultrasound attenuation (BUA), speed of sound (SOS) and quantitative ultrasound index (QUI) of the calcaneus were measured using the Sahara ultrasound device. Significant declining with age was found for all three parameters (p < 0.001). The peak SOS (1562.8 +/- 28.5 m/s) and QUI (103.6 +/- 16.5) values were observed in the third decade, whereas the peak BUA value (86.2 +/- 19.2 db/MHz) was observed in the fourth decade of life. Using the World Health Organization diagnostic criteria for DXA the rates of osteoporosis in the males aged 50 and older were 5.8%, 3.4 and 4.2% for QUI, BUA, and SOS respectively. However, when we used the cut-off value of the T < or = -l.8, prevalence of osteoporosis in Croatian males older than 50 years was 16.2%, 11.7% and 17.2%.

[Strontium ranelate--new paradigm in the treatment of postmenopausal osteoporosis]. / Stroncij ranelat--nova paradigma za lijecenje postmenopauzalne osteoporoze.

Osteoporosis has become a global public health issue due to the fact that the world population has gotten older. In the past ten years we have witnessed a great improvement in the treatment of postmenopausal osteoporosis. The anti-resorptive drugs are the most presribed ones. In the last couple of years osteoanabolic drug, a teriparatid, was introduced into the clinical use, and recently a strontium ranelate has occured as a drug with osteoanabolic and antiresorptive effect in bone formation. Clinical trials (phase III) have proved the efficiency of strontium ranelate in postmenopausal osteoporosis treatment. Strontium ranelate is a drug characterized by the new paradigm of action mechanism on bone, which has its place among the already well-proven drugs in postmenopausal osteoporosis treatment.

[Treatment of osteoporosis by risedronate-- speed, efficacy and safety]. / Brzina, ucinkovitost i sigurnost risedronata u lijecenju osteoporoze.

Risedronate (Actonel 35 mg), which was promoted in Croatia a few months ago, is the latest (III) generation of bisphosphonates, the most efficient anti-resorption drugs that inhibit osteoclast-mediated bone resorption and change the bone metabolism. The effect of risedronate is 10 times stronger than that of alendronate, and 10.000 times stronger than that of etidronate. The bone turnover is reduced while the osteoblast activity and bone mineralisation are preserved. Decreases in biochemical markers of bone turnover were observed as soon as within 1 month and reached a maximum in 3-6 months of Actonel 35 mg application once a week or 5 mg a day. Several major international, randomised and placebo controlled clinical studies (VERT-NA, VERT-MN, HIP...) on more than 15,000 patients over 3-5 years of therapy have confirmed the speed, efficacy and excellent tolerability of risedronate in treating postmenopausal and corticosteroid-induced osteoporosis. After only 6 months of treatment VERT-NA and VERT-MN have shown a significant reduction in vertebral fracture risk versus control group, radiographically by 62% and clinically by 69% in the first year, which remains significant even after 5 years of treatment (50%) of postmenopausal osteoporosis. All the best properties of bisphosphonates have also been confirmed through a significant reduction in the relative risk of femoral neck fracture over 3 years of treatment by 40%, or by as much as 60% in female patients with osteoporosis and prevalent vertebral fracture, compared with controls. With risedronate we can achieve a quick and significant reduction in vertebral fracture risk in postmenopausal women (65%), especially among a high-risk population such as patients on long-term glucocorticoid therapy (70%) in the very first year of treatment. Prevention and treatment of glucocorticoid-induced osteoporosis is recommended in the administration of 27,5 mg of prednisone or prednisone equivalent in a duration longer than 3 months, irrespective of age or gender. Tolerability and safety of risedronate administration in osteoporosis is very good, almost the same as in the control group, although patients with earlier described or ongoing gastrointestinal troubles were also included. The incidence of endoscopically confirmed gastric ulcer in treatment with alendronate is significantly higher (13,2%) versus controls than in treatment with risedronate (4,1%). Risedronate is hence the first line of bisphosphonates for the reduction of vertebral and non-vertebral fracture risks in postmenopausal women with osteoporosis or those with a high risk of osteoporosis. It also efficiently prevents bone loss or improves bone density in men and women on a long-term corticosteroid therapy.

[Osteoporosis in men]. / Osteoporoza u muskaraca.

Male osteoporosis represents an important public health problem. According to NHANES III (National Health and Nutrition Examination Survey), 7% of white men aged 50 years and over have osteoporosis. One-third of all hip fractures occurred in men and prevalence of death after hip fracture is twice as high as in women. Hypogonadism, alcohol abuse and glucocorticoid excess are the most frequent causes of secondary osteoporosis in men, while in 30-50% of cases osteoporosis is idiopathic. In the article we discuss etiology, epidemiology, diagnostic procedure and treatment of osteoporosis in men.

Folic acid and vitamin B(12) supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized, double-blind, placebo-controlled trial.

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B(12). The aim of this study was to determine whether there is an impact of folic acid and vitamin B(12) supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B(12) will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 µmol/L. Participants were randomly assigned to receive either a daily folic acid (800 µg) and vitamin B(12) (1000 µg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 µmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B(12) as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers.

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome.

Severe postoperative hypoglycemia in a patient with pheochromocytoma and preclinical Cushing's syndrome.

BACKGROUND: Postoperative hypoglycemia is not a common complication following the removal of a pheochromocytoma. Although the mechanism of hypoglycemia is not fully understood, it seems that it is caused by excessive rebound secretion of insulin after surgical resection of pheochromocytoma. CASE REPORT: We report a 43-year-old woman with a very rare association of pheochromocytoma and preclinical Cushing's syndrome (PCS) in the same adrenal gland who developed severe postoperative hypoglycemia. Pheochromocytoma was diagnosed by high serum and urine metanephrine and normetanephrine levels. PCS was characterized by blunted cortisol diurnal rhythm, low ACTH level, and failure of cortisol suppression by dexamethasone without any clinical signs of cortisol excess. In the early postoperative period after surgical removal of right adrenal gland, the patient lapsed into a stuporous state. The blood glucose level was 0.7 mmol/l. During the next 48 hours, normoglycemia was maintained with a continuous infusion of 20% glucose. On the third postoperative day, infusion was discontinued, oral feeds were introduced, and the plasma glucose level normalized. The patient did not have further episodes of hypoglycemia. Pathology revealed medullary pheochromocytoma and a cortical tumor of right adrenal gland. During the fifth postoperative day, plasma metanephrine and normetanephrine were 0.13 nmol/l and 0.30 nmol/l, respectively. Urinary metanephrine decreased to 0.5 pmol/24 h and normetanephrine to 2.8 micromol/24 h. CONCLUSIONS: This report indicates the importance of close monitoring of blood glucose level in a patient with pheochromocytoma after removal of an adrenal gland.

Selective estrogen receptor modulators: A possible new treatment of osteoporosis in males.

More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5alpha-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males.