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A rare case of massive osteolysis affecting the pelvis of a young girl is presented. The clinical, radiographic, and histopathological features are described in detail. Septicemia complicated the clinical course and the patient eventually died. Histopathological examination of the pelvic lesion revealed massive osteolysis characterized by prominent osteoclastic activity with extensive bone resorption. A thorough post-mortem histological examination of the thyroid gland showed no C cells. This is an interesting observation, since it is known that thyroid C cells are the primary source of calcitonin. Since the main biological effect of calcitonin is to inhibit osteoclastic bone resorption, there is a possibility that massive osteolysis in our case could have been related to the lack of this hormone. There is a clear need for further investigation regarding the role of thyroid C cells and calcitonin in this puzzling disease. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

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.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

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.

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 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.

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, Ivanić-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%.

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 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.

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.

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.

In the group of 13 patients with Cushing's syndrome (CS) CRH test was performed by sampling the blood from peripheral vein and in eight patients also after inferior petrosal sinus catheterization (IPSC) to resolve the disease etiology. In the group of patients with Cushing's disease (CD, n = 11), which was proven by surgery and adenoma immunohistochemistry, 10/11 had in CRH test the significant increase of cortisol and ACTH in the peripheral blood. Among two patients with ectopic ACTH syndrome one had the significant increase of both hormones in CRH test. After IPSC the ratio of ACTH in the petrosal sinus and in the peripheral vein was significant in 4/8 patients before, and in 6/8 after CRH administration. The intersinus gradient was significant in 3/8 patients before, and in 4/8 after CRH test. According to our results we can conclude that the determination of ACTH in the blood from peripheral veins after CRH administration is a very sensitive method for differential diagnosis of CS, while the results after IPSC were less sensitive in our conditions than those described in the literature.

Liddle's syndrome, apparent mineralocorticoid excess (AME) and glucocorticoid remediable aldosteronism (GRA) are inherited diseases characterized by hypertension and low plasma renin activity. Constitutive activation of distal renal epithelial sodium channel (Liddle's syndrome), defect in 11 beta-hydroxysteroid dehydrogenase activity (AME) and unequal crossing over, fusing regulatory sequences of 11 beta-hydroxylase gene to coding sequences of aldosterone synthase gene and forming a new chimeric gene (GRA), cause apparent or real mineralocorticoid excess. This diseases are often being unrecognized and classified as essential hypertension, especially in patients with normal serum potassium level. Family history of hypertension and characteristic serum and urine++ steroid profile direct us to diagnosis, and genetic analysis will confirm it.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

Androgen production in women is under the influence of pituitary hormones on ovaries and adrenal glands, or they originate from peripheral conversion of androgen precursor. Each of the three principal compartments of androgen production has a serum specific marker that may be clinically helpful. Serum testosterone signifies ovarian production, dehydroepiandrosterone sulfate (DHA-S) is an adrenal marker, and serum 3 alpha-diol glucuronide reflects androgen action in the peripheral compartment. Many physiologic and pathologic states affect transport proteins and enzyme systems which modulate androgenic activity. This fact makes the determination of mechanism and origin of hyperandrogenemia more difficult, as well as the choice of therapy. In the syndrome of hyperandrogenemia, the primary place of the disorder is determined by the tests of adrenal cortex and ovary functions. The correct response of androgens in dexamethasone test is manifested by free testosterone suppression to < 0.028 nmol/L, and by DHA-S and plasma cortisol suppression under the reference values. In the complex and controversial syndrome of hyperandrogenemia, the nafarelin test is used after insufficient free testosterone suppression in dexamethasone test. The significant diagnostic criterion is the rise of 17-hydroxyprogesterone (17-OHP) over 7 nmol/L, which aligns a great number of idiopathic hyperandrogenemias in the group of polycystic ovary syndrome. A good correlation was found between the rise of 17-OHP in nafarelin test and the suppression of free testosterone in dexamethasone test. This finding supports the conception that both tests determine the ovary function and that their sensitivity and specificity for ovary hyperandrogenemia is comparable.

The aim of this study was to establish the concentration of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I and growth hormone. IGF-I was determined in extracted serum or neat saliva by a disequilibrium RIA using antibodies and iodinated ligand from Amersham and WHO 87/518 as standard. The detection limit of the assay was 0.5 microgram/l, and the intra- and interassay coefficients of variations were 7.9% and 15% respectively. Our study included 13 healthy adult individuals and 17 acromegalics. Compared with healthy adult subjects, acromegalics had significantly higher salivary IGF-I concentrations (mean +/- SEM 5.4 +/- 2.64 vs. 10.5 + -5.69 micrograms/l; p < 0.01), as well as serum IGF-I (176 +/- 42.9 vs. 520 +/- 98.8 micrograms/l; p < 0.0001) and somatotropin levels (1.2 +/- 1.02 vs. 15.4 +/- 9.89 micrograms/l; p < 0.0001). However, 47.1% patients (8 out of 17) with active acromegaly had salivary IGF-I concentrations within the normal range. Serum IGF-I and somatotropin concentrations were found to follow more closely the disease activity after adenomectomy, compared with the concentrations of salivary IGF-I. These results suggest that the IGF-I levels in serum and saliva are somatotropin-dependent. According to our results, measurement of IGF-I in saliva cannot be considered as an additional measure for evaluation of the disease activity in acromegaly, being less reliable than the determination of IGF-I and somatotropin in serum.

Stress response measured as the cortisol secretion rate as well as urinary 17 oxogenic steroid (17 OGS) and 17 oxosteroid (17 OS) excretion was investigated in a group of 28 patients with stroke (11 with hypertensive intracerebral hemorrhage and 17 with ischemic cerebrovascular insult). Significantly higher cortisol secretion values were found in the group of patients who died (p less than 0.01). Similarly, the first day urinary 17 OGS excretion pointed to the greater adrenocortical response in patients who died (p less than 0.05). Urinary 17 OS excretion was normal or below normal in the majority of patients and no difference was found between either male or female patients who survived or died. Our findings indicate that adrenocortical changes which maximize the production of cortisol are operative soon after the onset of stroke. The cortisol secretion rate appeared to be a good indicator of the severity of the stress caused by stroke and may be useful in predicting the prognosis of the illness.

Successful treatment of diabetes mellitus requires a reliable control of glycaemia where self-monitoring with reflectometer plays a significant role. TRS-glucotest reflectometer (TRS, Zagreb), the result of our experts' efforts, makes it possible for diabetic patients to perform self-monitoring. According to our research TRS-glucotest reflectometer shows lower blood glucose levels for more than 20%, especially in 3.8-11.5 mmol/L range of glucose concentration, that is in the range most often expected in patients with diabetes got under control. A considerable dispersion of the results got by measuring glucose levels with reflectometer doesn't offer the possibility to correct the obtained values. Our results suggest that TRS-glucotest reflectometer should be improved so that reliable control of glycaemia can be made what is especially important in patients with intensive conventional insulin treatment.