[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

Epidemiology of hip fracture and the development of a FRAX model for Uzbekistan.

A prospective population-based survey in a region of the Republic of Uzbekistan determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Uzbekistan. OBJECTIVE: This paper describes the epidemiology of hip fracture in the Republic of Uzbekistan that was used to develop a country-specific FRAX® tool for fracture prediction. METHODS: During a 1-year (2016/17) prospective population-based survey in the Pap district of the Republic of Uzbekistan, hip fractures were prospectively identified from hospital registers, trauma centres and primary care and community sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Uzbekistan. Fracture probabilities were compared with those from neighbouring Kazakhstan and Kyrgystan. RESULTS: Approximately 41% of hip fracture cases did not come to medical attention, and two thirds of patients overall were not admitted to hospital. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 16,764 and is predicted to increase more than three-fold to 60,272 in 2050. FRAX-based probabilities were higher in Uzbekistan than Kazakhstan or Kyrgystan. CONCLUSION: The FRAX model should enhance accuracy of determining fracture probability among the Uzbek population and help guide decisions about treatment.

A surrogate FRAX model for the Kyrgyz Republic.

The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. INTRODUCTION: The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country. OBJECTIVE: This paper describes a surrogate FRAX model for the Kyrgyz Republic. METHODS: The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. RESULTS: Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75-80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. CONCLUSION: The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment.

Epidemiology of osteoporotic fracture in Kazakhstan and development of a country specific FRAX model.

Retrospective and prospective population-based survey in a region of the Republic of Kazakhstan determined the incidence of fractures at the hip, proximal humerus and distal forearm. The hip fracture rates were used to create a FRAX® model to enhance fracture risk assessment in Kazakhstan. OBJECTIVE: This paper describes the epidemiology of osteoporotic fractures in the Republic of Kazakhstan that was used to develop a country specific FRAX® tool for fracture prediction. METHODS: We carried out a retrospective population-based survey in Taldykorgan in the Republic of Kazakhstan representing approximately 1% of the country's population. Hip, forearm and humerus fractures were identified retrospectively in 2015 and 2016 from hospital registers and the trauma centre. Hip fractures were prospectively identified in 2017 from the same sources and additionally from primary care data. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Kazakhstan. Fracture probabilities were compared with those from neighbouring countries having FRAX models. RESULTS: The difference in hip fracture incidence between the retrospective and prospective survey indicated that approximately 25% of hip fracture cases did not come to hospital attention. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 11,690 and is predicted to increase by 140% to 28,000 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures in men but not in women. CONCLUSION: The FRAX model should enhance accuracy of determining fracture probability among the Kazakh population and help guide decisions about treatment.

Epidemiology of hip fracture in Belarus: development of a country-specific FRAX model and its comparison to neighboring country models.

Fracture probabilities resulting from the newly generated FRAX model for Belarus based on regional estimates of the hip fracture incidence were compared with FRAX models of neighboring countries. Differences between the country-specific FRAX patterns and the rank orders of fracture probabilities were modest. OBJECTIVE: This paper describes the epidemiology of hip fractures in Belarus that was used to develop the country-specific fracture prediction FRAX® tool and illustrates its features compared to models for the neighboring countries of Poland, Russia, and Lithuania. METHODS: We carried out a population-based study in a region of Belarus (the city of Mozyr) representing approximately 1.2% of the country's population. We aimed to identify all hip fractures in 2011-2012 from hospital registers and primary care sources. Age- and sex-specific incidence and national mortality rates were incorporated into a FRAX model for Belarus. Fracture probabilities were compared with those derived from FRAX models in neighboring countries. RESULTS: The estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 8250 in 2015 and is predicted to increase to 12,918 in 2050. The annual incidence of fragility hip fractures in individuals aged 50 years or more was 24.6/10,000 for women and 14.6/10,000 for men, standardized to the world population. The comparison with FRAX models in neighboring countries showed that hip fracture probabilities in men and women in Belarus were similar to those in Poland, Russia, and Lithuania. The difference in incidence rates between the surveys including or excluding data from primary care suggested that 29.1% of patients sustaining a hip fracture were not hospitalized and, therefore, did not receive specialized medical care. CONCLUSION: A substantial proportion of hip fractures in Belarus does not come to hospital attention. The FRAX model should enhance accuracy of determining fracture probability among the Belarus population and help guide decisions about treatment.

Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS.

This study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18 months. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall) and at 4, 12, and 18 months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture. RESULTS: Among 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (p < 0.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 p < 0.001) and vertebral fracture (0.70 vs. 0.83 p < 0.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types. CONCLUSIONS: Hip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18 months.

Epidemiology of fractures in Armenia: development of a country-specific FRAX model and comparison to its surrogate.

Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. OBJECTIVE: Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model. METHODS: We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country's population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011-2012 and prospectively in 2013 with the inclusion of primary care sources. RESULTS: The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new "authentic" FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models (> 0.99) so that the revisions had little impact on the rank order of risk. CONCLUSION: A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal.

[Lower extremity venous diseases in primary knee osteoarthritis]. / Patologiia ven nizhnikh konechnostei pri pervichnom osteoartroze kolennykh sustavov.

AIM: To establish a possible association between knee osteoarthritis (OA) and lower extremity venous diseases ((LEVDs) on the basis of thorough clinical and instrumental studies. SUBJECTS AND METHODS: A case-control study recruiting 40-60-year-old women was conducted. A study group included 85 women with knee OA; a control group consisted of 50 women without this condition. The patients of both groups underwent assessment of complaints and goal-directed objective examination to identify joint diseases and chronic LEVDs, knee X-ray study, and duplex scanning of the lower extremity veins. RESULTS: The patients with knee OA were more frequently diagnosed with lower extremity varicose vein disease (VVD) (43% vs 22%; p=0.015) and had signs of chronic venous insufficiency (28% vs 12%; p=0.03). Duplex scanning of the lower extremities showed that knee OA was characterized by generalized LEVD (bilateral valve lesions of the great and small saphenous veins and severe valvular incompetence in the veins) that was detected in 53% of the patients in this group versus 20% of the women in the control group (p = 0.0004). After adjustment for body mass index, the differences in the incidence of VVD between the groups remained clinically and statistically significant (odds ratio (OR), 2.7; 95% confidence interval, 1.1-6.7; p=0.036). CONCLUSION: The 40-60-year-old patients with knee OA more commonly develop symptoms of chronic venous insufficiency than their healthy peers. Although obesity is a risk factor for both diseases, there is an independent association between knee OA and lower extremity VVD.

Effect of twelve-month physical exercise program on patients with osteoporotic vertebral fractures: a randomized, controlled trial.

UNLABELLED: We performed a randomized clinical trial to evaluate the effect of a 12-month physical exercise program on quality of life, balance, and functional mobility in postmenopausal women with osteoporotic vertebral fractures. All three outcomes improved in the intervention group and were better than in the controls. INTRODUCTION: Th aim of this study was to evaluate the effectiveness of a structured physical exercise intervention on quality of life, functional mobility, and balance in patients with osteoporotic vertebral fractures and back pain. METHODS: Seventy-eight postmenopausal women with vertebral fractures were randomized into an exercise group (n = 40) and a control group (n = 38). The mean age was 69.2 ± 7.7 years. All women had at least one osteoporotic vertebral fracture and suffered from chronic back pain. Patients with a history of vertebral and non-vertebral fracture within the past 6 months were excluded. The 40-min exercise program was conducted twice weekly for 1 year. Participants in the control group were instructed to continue their usual daily activities. Participants were assessed at baseline and at 12 months using the Quality of Life Questionnaire (QUALEFFO-41). Balance was measured with the Balance Master® System NeuroCom® and functional mobility was measured with the "timed up and go" test and "sit-to-stand" test. RESULTS: Total QUALEFFO-41 score after 12 months was significantly better in the exercise group (44.2 ± 7.5) compared to the control group (56.6 ± 9.4), p < 0.0001. Quality of life improved in domains: "Pain", "Physical function: Jobs around the house", "Physical function: Mobility", "Social function", "General health perception" in the exercise group as compared to the control group. After 12 months, balance as assessed by "Tandem Walk and Sway" became significantly better in the exercise group as compared to the control group (p = 0.02). A significant improvement in the "timed up and go" test (p = 0.02) and the "sit-to-stand" test (p = 0.01) was shown in the exercise group compared to the control group. CONCLUSIONS: This is the first 12 month-randomized clinical trial of exercise in osteoporotic women with a vertebral fracture that demonstrates improvement of three key outcome measures: quality of life, functional mobility, and balance.

[Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)].

AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures.

The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)--quality of life during the first 4 months after fracture.

UNLABELLED: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. METHODS: ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. RESULTS: The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. CONCLUSIONS: The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis.

UNLABELLED: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. INTRODUCTION: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. METHODS AND RESULTS: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. CONCLUSIONS: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.

Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia.

PURPOSE: Vitamin D deficiency leads to secondary hyperparathyroidism and osteomalacia, and both conditions are associated with fractures, the most severe being hip fracture. The serum 25-hydroxyvitamin D level depends on latitude and season. Yekaterinburg is situated at a high latitude and the duration of winter is about 5 months. METHODS: In this study, the serum 25(OH)D and PTH concentrations, and the prevalence of hypovitaminosis D in elderly people, inhabitants of Yekaterinburg, were investigated. The study was performed on 63 people with hip fracture (mean age, 68.8 years) and 97 independently living elderly people (mean age, 70.2 years). RESULTS: Serum 25(OH)D (mean+/-SD) in the hip fracture group was 22.4+/-11.4 nmol/L, significantly lower than in control group, which was 28.1+/-10.1 nmol/L. The percentage of patients with severe hypovitaminosis D (<25 nmol/L) in the hip fracture group was 65%, compared to 47% in the control group (p<0.05). The prevalence of hypovitaminosis D among hip fracture patients, as well as among independently living elderly people in Yekaterinburg, was high. CONCLUSION: Supplementation of vitamin D in elderly people with and without fracture might prevent secondary hyperparathyroidism, osteomalacia and fractures.

Clinical features of Lyme borreliosis in the middle Urals and distribution of Borrelia burgdorferi sensu lato species in local Ixodes persulcatus ticks.

From 1991 to 1993, we investigated the clinical features of Lyme borreliosis (LB) in 864 patients from the Sverdlovsk region (population 4.5 million) in the middle Urals. Ixodes persulcatus ticks were collected in the vicinity of Yekaterinburg to determine the presence of Borrelia burgdorferi sensu lato species. From 1991 to 1993, the number of patients with LB increased from 91 to 320 and 453, respectively. Nearly all LB patients (97%) recalled a tick bite and the first signs of LB developed between May and August. Erythema migrans (EM) was seen in 820 patients (94.9%) and fever was common (44.6%). Neuroborreliosis, mainly radiculoneuritis, was found in 154 patients (17.8%), secondary erythema was seen in 53 patients, and Lyme arthritis (LA) was diagnosed in 35 patients. Carditis was rare and acordermatitis chronica atrophicans (ACA) was not seen. Only 44 patients developed one or more symptoms of LB without a preceding EM. Few patients were seropositive for tick-borne encaphalitis. Borrelial DNA was detected in 67% of I. persulcatus ticks. Infected ticks carried predominantly Borrelia garinii or Borrelia afzelii, mixed infections of both species were common. Borrelia valaisiana was detected once, and B. burgdorferi sensu stricto was not found. Although the course of LB in the middle Urals in comparable to that of European LB, several discrepancies were noted. LB patients often recall tick bites, fever is common, LA is mild and ACA is absent.

Does chlamydia trachomatis influence manifestations of Lyme Arthritis?

Lyme arthritis, caused by the tick-borne spirochete Borrelia burgdorferi, produces typically intermittent episodes of arthritis of the larger joints, usually the knee joints. A number of patients, however, develop arthritis more closely resembling Reiter's syndrome, i.e., heel and ankle involvement. We studied the clinical features of ten patients who developed arthritis after a tick bite and who had shown erythema migrans and related it to the presence of evidence of Chlamydia trachomatis infection. Along with typical signs of Lyme arthritis we observed heel and ankle involvement. Chlamydia trachomatis was found in smears in 4 cases, whereas no patient had antichlamydial antibodies. However, evidence of Chlamydia trachomatis did not correlate with signs considered typical of Reiter's syndrome. Therefore, Lyme arthritis may have some arthritic manifestations resembling Reiter's syndrome, but this seems unrelated to the presence of Chlamydia trachomatis. Moreover, the arthritis is not associated with HLA-B27.