Clinical Management of Women with Newly Diagnosed Osteoporosis: Data from Everyday Practice in Bulgaria.

INTRODUCTION: The real duration of osteoporosis treatment in clinical practice is still not well described. The primary objective is to estimate the proportion of patients who stayed on treatment during a 4-year follow-up, and the secondary objective is to estimate the proportion of patients who switched treatment and the reasons for switch or discontinuation. METHODS: This was a national retrospective chart review, based on routine clinical data. Data were collected electronically from medical records in 33 representative primary care physicians' sites. Inclusion criteria were women with postmenopausal osteoporosis that have received initial treatment prescription following diagnosis by DXA between January 1, 2012 and December 31, 2014, and at least a 12-month database history after the index date. Exclusion criteria were women receiving treatment for osteoporosis and follow-up at secondary care physicians' sites only. All statistical analyses were performed with the R statistical package. RESULTS: A total of 1206 female patients with newly diagnosed osteoporosis and treatment initiation were followed for 4 years. The majority (88.3%) had no history of previous fractures. Bone mineral density data were available in 70.1%. Endocrinology was the most common specialty among prescribing specialists (40.0%), followed by rheumatology (30.3%). Bisphosphonates (BPs) were the most common initial treatment (72.7%), followed by denosumab (20.1%). Ibandronate (70.2%) and alendronate (24.2%) constituted the majority of all prescribed BPs; 731 patients remained on treatment during the second year (60.6%), 524 during the third year (43.4%) and 403 (33.4%)-at study end (fourth year). In all groups, except that on denosumab, the most common reason for switching to another treatment was presumed lack of effect. The main reasons for treatment discontinuation were financial on the patient's part. CONCLUSIONS: The duration of osteoporosis treatment in real-world clinical practice is far from optimal: < 3-4 years irrespective of fracture risk. Factors other than medical considerations are at play, mainly limitations set by the Health Insurance Fund. The health authorities should be aware of this.

Trends in the epidemiology of thyroid diseases in Bulgaria since the year 2000-a review of the literature.

This review attempts to summarize data on the prevalence of thyroid pathology in the Bulgarian population over a period of 20 years. Thyroid dysfunction was studied in two population-based studies (2006 and 2012). In the first, hypothyroidism was found in 6.3% and hyperthyroidism in 3.7% of the participants. The second study found overt and subclinical hypothyroidism in 3.2% and 4.5%, respectively, of females, and in 1.1% and 2% of males. TPOAb levels were elevated in 23% of females and in 9.6% of males. Nodules were found using ultrasound (US) in 23.4% of the participants in the 2006 study (in 30.1% of females and 15.0% of males), while the 2012 study showed 24.4% (32.1% of females and 15.7% of males). Recent data regarding prevalence of thyroid carcinoma in the Bulgarian population are lacking. Between 4 and 6% of thyroid biopsies produce results which have markers for malignancy. Four studies were carried out to address urinary iodine excretion levels in schoolchildren and three for those in pregnant women. Although median urinary iodine was in the iodine-sufficient range, a rising proportion of women had low urinary excretion. In the studies involving schoolchildren, excessive iodine excretion was also observed. The major strength of this review is the combination of data from different publications to give an overall baseline of thyroid epidemiology in Bulgaria. Further work is needed to map the recent trends regarding thyroid pathology in Bulgaria and the complete epidemiological dataset.

Thyroglossal duct cyst carcinoma.

Not required for Clinical Vignette.

One-year mortality after severe COPD exacerbation in Bulgaria.

INTRODUCTION: One-year mortality in COPD patients is reported to be between 4% and 43%, depending on the group examined. AIM: To examine the one-year mortality in COPD patients after severe exacerbation and the correlation between mortality and patients' characteristics and comorbidities. METHODS: A total of 152 COPD patients hospitalized for severe exacerbation were assessed for vitamin D status, diabetes mellitus (DM), arterial hypertension (AH), and metabolic syndrome (MS). Data were gathered about smoking status and number of exacerbations in previous year. CAT and mMRC questionnaires were completed by all patients. Pre- and post-bronchodilatory spirometry was performed. One-year mortality was established from national death register. RESULTS: One-year mortality is 7.2%. DM, MS, and VD are not predictors for one-year mortality. However there is a trend for increased mortality in patients with AH (9.5% vs. 2.1%, p = 0.107). There is increased mortality in patients with mMRC > 2 (11.1 vs. 0%, p = 0.013). The presence of severe exacerbation in the previous year is a risk factor for mortality (12.5% vs. 1.4%, p = 0.009). There is a trend for increased mortality in the group with FEV1 < 50% (11.5 vs. 4.4%, p = 0.094). Cox regression shows 3.7% increase in mortality rate for 1% decrease in FEV1, 5.2% for 1% decrease in PEF, 7.8% for one year age increase and 8.1% for 1 CAT point increase (all p < 0.05). CONCLUSIONS: This study finds relatively low one-year mortality in COPD patients after surviving severe exacerbation. Grade C and FEV1 > 80% may be factors for good prognosis. Risk factors for increased mortality are age, FEV1 value, severe exacerbation in previous year and reduced quality of life.

Diabetes Mellitus Type 2 in Hospitalized COPD Patients: Impact on Quality of Life and Lung Function.

INTRODUCTION: Diabetes mellitus (DM) is estimated to affect 2-37% of COPD patients, results varying widely between studies. DM may also correlate with quality of life and lung function. AIM: To examine correlations between DM and quality of life and lung function in COPD patients admitted to hospital with exacerbation of COPD. PATIENTS AND METHODS: A hundred and fifty-two patients were included in the study. They were all examined for diabetes mellitus. All patients completed CAT and mMRC questionnaires and underwent spirometry. RESULTS: 13.2% (20/152) of patients received medications for DM. 21.7% (33/152) had newly diagnosed DM and 30.9% (47/152) had prediabetes. DM is not associated with reduced quality of life and worse pulmonary function. However, untreated DM is associated with both reduced quality of life and worse pulmonary function. HbA1c is negatively correlated with FVC and positively correlated with CAT score. CONCLUSIONS: COPD patients hospitalized for exacerbation are at high risk for impaired glucose metabolism. Untreated DM is associated with worse lung function and lower quality of life, which stresses the importance of screening for the disease. The patients may benefit from optimizing blood glucose level.

Polymorphisms of the human IL-1 receptor antagonist gene and forearm bone mineral density in postmenopausal women.

CONTEXT: Studies on the human interleukin 1 receptor antagonist (IL-1RA) gene polymorphism have provided conflicting data regarding the bone mass and quality. AIM AND DESIGN: The objective of this case-control study was to investigate the association between the forearm bone mineral density (BMD) and the IL1RA gene polymorphisms. MATERIALS AND METHODS: A total of 400 postmenopausal Bulgarian women participated in this study. BMD was measured at the forearm by X-ray absorptiometry on a DTX-100 device (Osteometer Meditech, USA). A PCR product was isolated. The alleles were scored according to their length: A1 - 410 bp - 4 repeats; A2 - 240 bp - 2 repeats; A3 - 500 bp - 5 repeats; A4 - 325 bp - 3 repeats; A5 - 595 bp - 6 repeats. All analyses were evaluated for statistical significance (χ(2)-test and T-test). RESULTS: Four alleles were observed - A1, A2, A3, and A4. The A1A1 genotype was more common in cases with low BMD than in controls with normal BMD (95% vs. 90%, χ(2)P < 0.01). The A2A2 genotype was equally distributed among cases and controls (both 5%). The other two genotypes (A3A3 and A4A4) as well as A1A3 were present only in controls with normal BMD. The A2A2 genotype was associated with higher BMD and the A1A1 - with lower BMD at both forearm sites. The odds ratio for low BMD in the presence of the A1A1 genotype was 2.11. The etiological factor reflecting the association between the polymorphism and the disease was 0.50. In our study sample the IL1RA genetic polymorphisms were associated with the forearm BMD. CONCLUSION: This genetic polymorphism may become a useful genetic marker for the study of osteoporosis.

Prevalence of low forearm bone mineral density in Bulgarian men: a pilot study.

OBJECTIVE: To determine the prevalence of osteoporosis at the distal forearm in a male cohort referred for bone density testing and to compare it to published data of Bulgarian women. DESIGN AND SUBJECTS: 315 consecutive Bulgarian men aged 20 to 84 years were included (mean age 53.74 +/- 14.67 years). 59% of them were self-referrals. The comparative female group consisted of 8869 Bulgarian women whose forearm bone mineral density (BMD) was measured in another study. MEASUREMENTS: BMD was measured by single X-ray absorptiometry at the distal forearm (distal and ultradistal sites) in all men. T-scores were calculated from manufacturer-provided Danish male reference data. RESULTS: The ratio of female to male patients was 28.2 (8869 to 315). Peak BMD was observed in men aged 30 to 39 years: 0.560 +/- 0.065 g/cm(2) (distal site) and 0.490 +/- 0.070 g/cm(2) (ultradistal site). A steady BMD decline followed reaching 0.492 +/- 0.064 g/cm(2) at the distal and 0.412 +/- 0.069 g/cm(2) at the ultradistal site in age group >70. Age had a rather weak negative impact on forearm BMD described by a linear model. In men aged over 50 years the prevalence of osteoporosis at the distal site was 21.19%, compared to 20.45% in women. Low bone mass was seen in 48.77% of men and 32.50% of women. Normal BMD was more frequent in women (47.05%) than in men (30.04%). CONCLUSIONS: We found a high prevalence of forearm osteoporosis in Bulgarian men which is comparable to that already known in women.

PvuII and XbaI polymorphisms of the estrogen receptor gene and bone mineral density in a Bulgarian population sample.

OBJECTIVE: The aim of this study was to search for a possible association of low bone mineral density (bMD) with the PvuII and XbaI polymorphisms of the estrogen receptor (Er) gene in bulgarian women. DESIGN: 400 bulgarian women participated in this study. bMD was measured at the lumbar spine, femoral neck and at the distal forearm. two groups were identified: women with normal bMD at both central sites (n=180) and women with low bMD at either site (n=220), designated as normal (NbMD) and low bMD (LbMD) groups, respectively. the genotype frequencies of PP, Pp, pp and XX, Xx, xx were investigated by Pcr and enzymatic digestion of the products by PvuII and XbaI. RESULTS: The genotype frequencies were 12% for the PP, 59% for the Pp and 29% for the pp genotypes in the NbMD, and 26%, 50% and 24% in the LbMD groups, respectively. the XX, Xx, xx genotype frequencies were 14%, 63% and 23% in the NbMD, and 33%, 50% and 17% in the LbMD groups, respectively. the various genotypes were significantly associated with bMD. the relative risk for low bMD was higher for the XbaI marker (rr=1.51) than for the PvuII marker (rr=1.35). the association between low bMD and the polymorphisms under study was described by an etiological factor of 0.28 for the XbaI marker and 0.20 for the PvuII marker. CONCLUSIONS: The specific XbaI and PvuII polymorphisms of the Er gene are associated with low bMD at all bMD measurement sites in the bulgarian female population. they might therefore become useful genetic markers in osteoporosis risk assessment in this specific population.

Prevalence of low central bone mineral density in a Bulgarian female referral population: a pilot study.

Osteoporosis is one of the most important health problems among elderly women. The prevalence of central osteoporosis in Bulgaria is still unknown. We tried to retrospectively determine the prevalence of osteopenia and osteoporosis at the spine and hip in a female referral population. Bulgarian women (2,600) aged group 25-87 years referred for bone densitometry screening were included. Information about known risk factors for low bone mass was recorded. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500 A) at the lumbar spine (2,547 participants, 1,954 of whom were postmenopausal) and left hip (723 participants, 605 of whom were postmenopausal). T-scores were calculated from Hologic-provided and own Bulgarian peak BMD data (the latter based on 122 healthy premenopausal 25- to 39-year-old women). Peak lumbar spine BMD was 0.994 g/cm2 (SD 0.095 g/cm2), and thus lower than the manufacturer-provided value of 1.047 g/cm2. The peak BMD of the total hip was 0.959 g/cm2 (SD 0.129 g/cm2) and thus higher than the manufacturer-provided BMD of 0.942. T-scores differed according to the database used. The osteoporosis threshold of -2.5 SD was reached at the spine in the age group 70-74 years. Left hip T-scores showed a much slower decline with age. In women aged 50 and older the prevalence of osteoporosis reached 37.31% at the spine, and 16.14% at the left hip. Osteopenia was found in 39.74% at the spine and in 65.57% at the total hip. This is the first Bulgarian study looking for the prevalence of central osteoporosis in a female referral population. It may become the starting point for future epidemiological work.

Prevalence of the metabolic syndrome in a Bulgarian female population referred for bone density testing.

OBJECTIVE: To investigate the prevalence of the metabolic syndrome in Bulgarian women referred for bone density screening. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional clinical study. Subjects were 444 consecutive 30- to 75-year-old Bulgarian women recruited from the outpatients referred for bone density testing (mean age, 52.67 +/- 15.19 years; mean BMI, 26.10 +/- 5.71 kg/m2. Height (centimeters), weight (kilograms), and blood pressure were measured. BMI and waist-to-hip ratio were calculated. Fasting plasma glucose, blood lipids, and immunoreactive insulinemia (Bayer Corp.-Diagnostics Div., Tarrytown, NY) were determined. Body composition was analyzed by bioimpedance on a leg-to-leg analyser (Tanita TBF-215; Tanita Corporation, Tokyo, Japan). RESULTS: Of all women, 56.76% had a BMI > 25 kg/m2, 45.95% had a waist circumference > 88 cm, and 64.64% had a waist-to-hip ratio > 0.8; 59.90% had hypertension; 4.05% had fasting plasma glucose > 7.0 mM, and 42.79% had fasting morning immunoreactive insulinemia = 16 UI/liter; 23.65% had hypercholesterolemia; and 26.35% had hypertriglyceridemia. The prevalence of the metabolic syndrome in this sample, as defined by the National Cholesterol and Education Program-Adult Treatment Panel III, was 34.91%, and by the modified World Health Organization definition was 37.16%. DISCUSSION: We concluded that Bulgarian women 30 to 75 years old referred for bone density testing have a high prevalence of the metabolic syndrome. Therefore, large-scale prevention programs are needed in this field.

Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study.

OBJECTIVE: We investigated the effects of 1-year tibolone treatment on body weight, body composition and indices of android obesity in postmenopausal women. METHODS: Forty-four postmenopausal women participated in this open-label controlled study; mean age was 51.8+/-2.21 years and all women were menopausal for 3.8+/-1.40 years. Twenty-two of them started taking 2.5 mg tibolone (TIB) daily for 1 year, whereas the remaining 22 served as age-matched controls. All subjects underwent a structured interview, physical examination, body composition measurements performed by dual-energy X-ray absorptiometry (DXA) - Hologic QDR 4500 A, as well as bioelectrical body impedance analysis (BI) - Tanita TBF-215, Japan. RESULTS: The TIB group did not significantly increase their weight (+0.4 kg), while the non-treated controls increased their mean weight by 1.4 kg (p=0.046). In the TIB group, DXA showed a non-significant body fat decrease by a mean of 0.5 kg and a non-significant lean mass increase by 0.8 kg, while in the control group, fat mass increased by 1.7 kg (p=0.032) and lean mass did not change. BI revealed that the TIB group had lost some fat ( approximately 0.6 kg, n.s.) and put some free-fat mass ( approximately 1.0 kg, p=0.048) without changes in total body water. The control group put on some fat ( approximately 1.1 kg, p=0.042) and lost some body water ( approximately 0.4 kg, n.s.). CONCLUSION: Results from both methods of measuring body composition show a similar trend: a decrease in fat mass and an increase in lean mass in TIB treated subjects. From the body composition perspective, tibolone may be regarded as a preferential alternative to conventional hormonal therapy (HT) in postmenopausal women.

Determinants of thyroid volume in schoolchildren: fat-free mass versus body fat mass--a cross-sectional study.

OBJECTIVE: To investigate the relationship between thyroid volume and body composition in schoolchildren 11 to 15 years of age. METHODS: We conducted a cross-sectional study of 126 girls and 86 boys who were living in an urban area and receiving iodine supplementation. The medical history was reviewed. Weight, height, body fat, fat-free mass, and total body water were measured by using a tetrapolar bioelectrical impedance analyzer. Body mass index and body surface area were calculated. Iodine excretion was measured in a morning urine sample by spectrophotometry. Thyroid volume was measured with use of an ultrasound scanner. Thyroid-stimulating hormone was measured from capillary blood samples with use of a neonatal human thyrotropin kit. RESULTS: All study participants were euthyroid. No study participant had urinary iodine excretion of less than 10 mg/L, and two thirds of the study group had iodine excretion of more than 100 mg/dL. Mean thyroid volume increased from 5.35 +/- 1.11 mL in boys at age 11 years to 8.52 +/- 3.32 mL in boys at age 15 years and from 5.95 +/- 1.70 mL to 7.53 +/- 1.92 mL in girls of corresponding ages. In both sexes, thyroid volume correlated better with height (r = 0.33 in girls and 0.50 in boys), weight (r = 0.35 and 0.43, respectively), and body surface area (r = 0.38 and 0.50, respectively) than with body mass index (r = 0.26 and 0.16, respectively). Thyroid volume showed a significant correlation with fat-free mass (r = 0.39 in girls and 0.49 in boys) and no significant correlation with body fat in both girls and boys. CONCLUSION: Thyroid volume is dependent on body size and therefore on growth variables. It depends on fat-free mass as a relatively precise measure of body size and is not related to the fat mass.